A pre-operative magnetic resonance imaging (MRI) scan of the brain with and without contrast is required; NOTE: computed tomography (CT) scans are NOT sufficient for study eligibility* Post-operative head MRI scan with and without contrast (preferably within 72 hours post-surgery); for patients who undergo stereotactic biopsy only, either a pre or post-operative MRI is sufficient; for patients with M2 and M3 disease, a post-op MRI is strongly encouraged, but not mandatory* Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done pre-operatively or within 28 days of surgery if done post-operatively; for posterior fossa tumors, pre-operative MRI scans are preferred
Lumbar cerebrospinal fluid (CSF) cytology examination must be obtained pre-operatively or within 31 days following surgery; the optimal time for obtaining CSF is prior to surgery or 1-3 weeks following surgery; ventricular CSF (either pre- or post-op) may be used only if a post-operative spinal tap is contraindicated; if a spinal tap is contraindicated and there is no ventricular CSF available, then CSF cytology can be waived for patients with supratentorial tumors or if there is documentation of spinal subarachnoid metastases (M3); patients who are categorized as M1 must have either an intra-operative positive CSF (via lumbar puncture at the end of the procedure) or a positive lumbar CSF obtained > 7 days post-operatively
CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution when taking cyclophosphamide; aprepitant should also be used with caution with etoposide or vincristine chemotherapy
Cisplatin should be used with caution with nephrotoxic drug; aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided; patients receiving cisplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity* Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with cisplatin
Limited stage disease patients, with disease restricted to one hemithorax with regional lymph node metastases, including ipsilateral hilar, ipsilateral and contralateral mediastinal, and ipsilateral supraclavicular lymph nodes* Patients with disease involvement of the contralateral hilar or supraclavicular lymph nodes are not eligible* Patients with pleural effusions that are visible on plain chest radiographs, whether cytologically positive or not, are not eligible unless they have a negative thoracentesis* Patients with cytologically positive pleural or pericardial fluid, regardless of the appearance on plain x-ray, are not eligible
Patients with complete surgical resection of disease are not eligible
Patients must have achieved a documented complete response to treatment based on normal cancer antigen (CA)-125 (per the institution�s upper limit of normal) and computed tomography (CT) scan or magnetic resonance imaging (MRI) with contrast (i.e. there must be no clinical evidence of persistent or recurrent disease based on CA-125 and CT scan or MRI with contrast)
Patients must not be currently enrolled in an ongoing (participating for 6 months or longer) medically prescribed diet or physical activity regimen
Patients must have no other chronic disease that would preclude randomization into a lifestyle intervention trial; such diseases include recent myocardial infarction or unstable angina (in the previous 6 months), chronic hepatitis, rheumatoid disease, renal or hepatic disease/dysfunction and diabetics receiving insulin; or other clinical condition limiting ability to walk (recent leg fracture, significant osteoarthritis, related orthopedic conditions, degenerative neurological conditions, etc.)
Patients must not have a serious psychiatric illness (e.g. lifetime bipolar disorder, schizophrenia or other psychosis, serious personality disorder, severe major depressive disorder or recent suicide or psychiatric hospitalization) (previous 12 months), or a history of an eating disorder (anorexia nervosa or bulimia nervosa)
Patients must complete all pre-entry assessments
Patients must be willing to provide name and appropriate telephone contact information and be willing to be contacted periodically via telephone by The University of Arizona Cancer Center (AZCC) staff for completion of individualized lifestyle intervention coaching, completion of the Pittsburgh Sleep Quality Index, and for clarification of patient-completed responses if necessary; patient must be willing to have Arizona Food Frequency Questionnaire (AFFQ), Arizona Physical Activity Questionnaire (APAQ), baseline questionnaire, and personal contact information sent to AZCC
Patients with body mass index (BMI) < 20 kg/m^2
Vegan vegetarians
Patients enrolled in a weight loss program or who are taking weight loss medications or dietary supplements and are unwilling to discontinue
Patients who have participated in a marathon, triathlon, or other endurance-related physical activity within the previous 24 months
Patients who have had surgery for weight loss* Note: women will not be excluded if their baseline lifestyle assessment indicates a healthy eating and moderate physical activity with the exception of the exclusion criteria above
All patients must have undergone complete hysterectomy and bilateral salpingo-oophorectomy at the time of original therapy for their uterine carcinoma
Patients must have no evidence of extrapelvic disease; complete workup staging should be performed prior to initiation of therapy to rule-out presence of metastatic disease; this should include: computed tomography (CT) scan of the thorax with IV contrast, as well as a CT of the pelvis and abdomen with IV and oral (PO) contrast performed using multi-detector CT and equal or less than 5 mm slice thickness; if the patient is unable to tolerate contrast, then magnetic resonance imaging (MRI) with IV gadolinium should be performed; a chest x-ray should be done first, and if abnormal, then a CT scan of the chest should be done
Primary surgical debulking before protocol therapy is permissible; this would include removal of gross symptomatic disease in the pelvis and/or vagina* Exenterative surgery is not permissible; patients with complete resection of gross recurrent disease are eligible
Patients must have an estimated survival greater or equal to 3 months
Patients with ureteral obstruction must undergo stent or nephrostomy tube placement prior to study entry
Patients who have met the pre-entry requirements
Patients with evidence of disease outside of the pelvis, including presence of positive periaortic or inguino-femoral nodes
Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields
Patients who have undergone complete surgical resection of the recurrent tumor and have no evidence of residual disease evaluable clinically and by CT or MRI imaging, following resection
Patients with history of active collagen vascular disease
Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma and primary mediastinal B cell lymphoma
Any stage for mediastinal gray zone lymphoma (MGZL) and primary mediastinal B cell lymphoma (PMBL)
Absolute neutrophil count (ANC) > 1000 unless impairment is due to lymphoma or immune-mediated mechanism caused by lymphoma
Platelets > 100,000 unless impairment is due to lymphoma or immune-mediated mechanism caused by lymphoma
No other serious concomitant medical illnesses or uncontrolled active infection that would jeopardize the patient's ability to receive the regimen with reasonable safety
Patients enrolled on the expansion portion of the study will consist of two cohorts: those patients who are triple-negative, BRCA-mutant positive and those patients who have triple-negative, non-BRCA mutated breast cancer
Patients must have tumors determined to be easily accessible for biopsy (e.g. pleural-based lesions, peripheral lymph nodes, soft tissue metastases, large liver metastases, etc)
History of allergic reactions attributed to the following: * Camptothecin derivatives (e.g., topotecan [topotecan hydrochloride], irinotecan, or exatecan [exatecan mesylate]) * Any ingredients contained within the liquid irinotecan solution (e.g., sorbitol) or* Any antiemetics or antidiarrheals appropriate for administration with study therapy (e.g., loperamide or dexamethasone)
Patients with uncontrolled seizures
Any patient requiring chronic maintenance of white blood cell counts or granulocyte counts through the use of growth factor support (e.g. Neulasta, Neupogen)
Willingness to provide the biologic specimens is required by the protocol; this is part of the mandatory correlative research component; these specimens include:- PHASE I: peripheral blood for plasma pharmacokinetic analysis and peripheral blood mononuclear cell (PBMC) polymer assessment from 0-24 h after drug administration on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; urine for assessment of ABT-888 renal clearance for 24 h after administration of drugs on days 1 and 2 of cycle 1 as well as day 2 of cycle 2; and a pretreatment peripheral blood sample for possible sequencing of the BRCA1, BRCA2 loci as well as possible pharmacogenomic analysis
Known standard therapy for the patient�s disease that is potentially curative or definitely capable of extending life expectancy
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Clinical stage T1, N1-2 or T2-4a, N0-2, M0 including no distant metastases, based upon the following minimum diagnostic workup:* General history and physical examination by a radiation oncologist and/or medical oncologist within 8 weeks prior to registration* Examination by an ear, nose and throat (ENT) or head & neck surgeon, within 8 weeks prior to registration; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is recommended but not required* Chest x-ray (at a minimum) or chest computed tomography (CT) scan (with or without contrast) or CT/positron emission tomography (PET) of chest (with or without contrast) within 8 weeks prior to registration
Gross total resection of the primary tumor with curative intent must be completed within 7 weeks of registration with surgical pathology demonstrating one or more of the following �intermediate� risk factors:* Perineural invasion* Lymphovascular invasion* Single lymph node > 3 cm or >= 2 lymph nodes (all < 6 cm) (no extracapsular extension)* Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin, and/or an initially focally positive margin that is subsequently superseded by intraoperative negative margins; similarly, patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient* Pathologically confirmed T3 or T4a primary tumor; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient* T2 oral cavity cancer with > 5 mm depth of invasion
Absolute granulocyte count (AGC) >= 1,500/mm�
The following assessments are required within 2 weeks prior to the start of registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator�s discretion
Per the operative and/or pathology report, positive margin(s) (defined as tumor present at the cut or inked edge of the tumor), nodal extracapsular extension, and/or gross residual disease after surgery; note: patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient
Prior allergic reaction to cetuximab
Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance)
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study
Participant with unilateral or bilateral neck dissection planned for care; an N0 neck must be planned to be dissected for the patient to be eligible; the N0 neck can be either ipsilateral to the head and neck tumor or the contralateral N0 neck if a bilateral neck dissection is planned
Participant with confirmed head and neck SCC:* CT and/or MR imaging has been completed within six (6) weeks prior to enrollment, even if the SCC diagnosis has been made via other methods, and will be submitted to American College of Radiology Imaging Network (ACRIN);* Simultaneous diagnostic CT with PET will not be excluded, but in such cases PET cannot be used as part of the criteria to define the N0 neck as required for entrance to the trial;* If sites received CT and/or MR images from institutions other than their own, ACRIN recommends a re-read by a local neuroradiologist to ensure compliance with protocol eligibility requirements
Participant with at least one neck that is clinically N0 as defined by clinical exam (physical exam with CT and/or MRI as the gold standard of the N0 neck); stages T2, T3, or T4. N0�N3, excluding N2c for bilateral disease based on criteria from the American Joint Commission on Cancer
Participant in whom it may be considered a viable clinical option to perform neck dissection when primary cancers are at high risk for neck metastasis (see definition above);* These will include: 1) oral cavity cancer; 2) oropharynx cancer, including base of tongue and tonsil cancers; 3) larynx cancer; or 4) supraglottic cancer
Patient with tumors in the head and neck that are not SCC
Patient with salivary gland malignancies
Patient not a candidate for surgery (neck dissection) because of an underlying medical condition
Patient who weighs more than the weight limit for the PET table
Patients must have undergone radical hysterectomy (open, laparoscopically or robotic) and staging including pelvic node sampling or dissection for cervical carcinoma within 70 days prior to study entry (NOTE: if the patient did not have a para-aortic lymph node sampling/dissection, but had common iliac node dissection that was negative, a positron emission tomography [PET]-computed tomography [CT] is recommended, but not required; a negative pre or post-operative PET scan or PET-CT scan of the para�aortic nodes is required if the patient did not undergo para-aortic or common iliac nodal sampling/dissection)
Patients with clinical stage IA2, IB or IIA squamous, adenosquamous, or adenocarcinoma of the cervix who have any/all of the following high-risk features after surgery:* Positive pelvic nodes* Positive parametrium* Positive para-aortic nodes- completely resected, PET/CT negative (PET only required if positive para-aortic nodes during surgery)
No distant metastases, based upon the following minimum diagnostic workup (NOTE: patients with positive para-aortic nodes- completely resected, PET/CT negative are eligible):* History/physical examination within 56 days prior to study entry* Contrast-enhanced imaging of the abdomen and pelvis by either CT, magnetic resonance imaging (MRI), or whole body PET-CT (with or without contrast) within 90 days prior to registration (NOTE: whole body PET-CT is preferred) * Chest x-ray (posterioranterior [PA] and lateral) or chest CT within 70 days prior to study entry (except for those who have had whole body PET-CT)
Bilirubin =< 1.5 times normal 14 days prior to study entry
Patients can not have any neuroendocrine histology in pathology
Prior allergic reaction to carboplatin, paclitaxel, and/or cisplatin
Patients must have a high grade urothelial carcinoma stage Ta or T1 that has recurred within 540 days after completion of the initial treatment (transurethral resection bladder tumor [TURBT] and intravesical bacillus Calmette-Guerin [BCG] immunotherapy) or on initial presentation with a T1 high grade tumor, the participating urologist judged BCG therapy is contraindicated or unsuitable because the patient is found to be intolerant of BCG therapy or because this patient may be immuno-compromised in ways other than that mentioned in severe, active co-morbidity or because the patient refuses BCG therapy
The participating urologist judges that the standard next therapy, based on present urologic guidelines for this patient, is radical cystectomy
Patients must have an adequately functioning bladder as judged by the participating urologist and radiation oncologist and have undergone a re-staging TURBT by the participating urologist that showed (or was present in the outside pathology specimen) a high grade stage Ta or T1 tumor with uninvolved muscularis propria in the specimen and, if on prostatic urethral biopsy mucosal carcinoma is present, there is no evidence on biopsy in the prostatic stroma of tumor invasion
Evidence of tumor-related hydronephrosis
Patients with pN+ or > T1 disease or who have not had a visibly complete TURBT
Patients receiving any drugs that have potential nephrotoxicity or ototoxicity (such as an aminoglycoside)
Prior allergic reaction to the study drugs (cisplatin, mitomycin, fluorouracil [5FU]) involved in this protocol
In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled on AHEP0731 without a biopsy* Clinical situations in which such emergent treatment may be indicated include, but are not limited to, the following circumstances:** Anatomic or mechanical compromise of critical organ function by tumor (eg, respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc)** Uncorrectable coagulopathy* For a patient to maintain eligibility for AHEP0731 when emergent treatment is given, the following must occur:** The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alpha fetoprotein, and must meet all AHEP0731 eligibility criteria at the time of emergent treatment** Patient must be enrolled on AHEP0731 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP0731 enrollment** If the patient receives AHEP0731 chemotherapy PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
Patients will be staged for risk classification and treatment at diagnosis using Children's Oncology Group (COG) staging guidelines
At the time of study enrollment, the patient�s treatment regimen must be identified; if the patient�s primary tumor was resected prior to the day of enrollment and a blood specimen for the determination of serum alpha fetoprotein was not obtained prior to that surgery, the patient will be considered to have alpha fetoprotein of greater than 100 ng/mL for the purpose of treatment assignment; if tumor samples obtained prior to the date of enrollment were not sufficient to determine whether small cell undifferentiated (SCU) histology was present, treatment assignment will be made assuming SCU is not present in the tumor
For patients with stage I or II disease, specimens for rapid central review have been submitted and the rapid central review diagnosis and staging must be available to be provided on the AHEP0731 eligibility case report form (CRF)
Patients may have had surgical resection of some or all sites of hepatoblastoma prior to enrollment
Normal pulmonary function tests (including diffusing capacity of the lungs for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); Note: for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
Prothrombin time (PT) < 1.2 x ULN
Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, warfarin and others) are not eligible
Patients who are currently receiving angiotensin-converting enzymes (ACE) inhibitors are not eligible
Histologic proof of primary head of pancreas invasive adenocarcinoma managed with a potentially curative resection (i.e., removal of all gross tumor) involving a classic pancreaticoduodenectomy (Whipple) or a pylorus preserving pancreaticoduodenectomy; patients with invasive adenocarcinoma that also contains a component of intraductal papillary mucinous neoplasm (IPMN) are eligible* The operating surgeon must document in the operative note that a complete gross excision of the primary tumor was achieved; the pathology report must include documentation of the margin status and the size of the tumor; the pathology report must also include the status of the three major margins�bile duct, pancreatic parenchyma, and retroperitoneal (uncinate)
Before starting therapy the patient should be able to maintain adequate oral nutrition of >= 1500 calories estimated caloric intake per day and be free of significant nausea and vomiting
Post resection serum cancer antigen (CA)19-9 =< 180 units/mL AND prior to any systemic treatment
Abdominal/pelvic computed tomography (CT) scan with contrast is preferred; abdominal CT alone is acceptable only if insurance restrictions are experienced; chest CT/x-ray (CT of chest preferred) within 31 days of registration on study (or within 31 days prior to day 1 of chemo post-surgery for those patients having started chemotherapy prior to first step registration); patients allergic to intravenous (IV) contrast can have magnetic resonance imaging (MRI) of the abdomen/pelvis instead
Consultation, agreement, and documentation in the patient�s chart by a radiation oncologist that patient is suitable to receive radiotherapy per this protocol
Patients with non-adenocarcinomas, adenosquamous carcinomas, islet cell (neuroendocrine) tumors, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas; patients with tumors that are largely IPMN with a minimal or minor component of invasive carcinoma are not eligible; patients with acinar carcinomas are not eligible; patients with IPMN�s that contain some secondary (minor) foci of adenocarcinoma are also not eligible
Patients managed with a total pancreatectomy, a distal pancreatectomy, or central pancreatectomy
If surgical margin status cannot be determined after consultation with the operating surgeon and the institutional pathologist, the patient will be ineligible
Patient must not have a concurrent active malignancy for which they are receiving treatment (other than myelodysplastic syndromes [MDS])
Patients with acute promyelocytic leukemia (APL) confirmed either by the presence of t(15;17)(q22;q21) or promyelocytic leukemia (PML)/retinoic acid receptor (RAR) alpha transcripts will be excluded
Patients must not have blastic transformation of chronic myelogenous leukemia
HLA typing should be performed at registration, if possible
CONSOLIDATION CRITERIA:
NOTE: All patients achieving CR or complete remission with incomplete blood count recovery (CRi) will receive consolidation when fit
NOTE: Patients proceeding to transplant are allowed up to one cycle of consolidation treatment
Patients must have achieved a CR or CRi (or morphologic leukemia-free state for those patients proceeding to Arm G transplant)
Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
MAINTENANCE CRITERIA:
Maintenance should commence within 60 days of recovery of peripheral blood counts after consolidation cycle 2; patients must begin consolidation cycle 2 within 60 days of recovery to be eligible for further therapy
The absolute neutrophil count (ANC) must be > 1000 mm^3 prior to starting every cycle of treatment with decitabine; decitabine may be delayed for up to 4 weeks between cycles (i.e. may be administered as infrequently as every (q) 8 weeks) while waiting for counts to recover
The platelet count must be > 75,000 mm^3 prior to starting every cycle of treatment with decitabine; decitabine may be delayed for up to 4 weeks between cycles (i.e. may be administered as infrequently as every (q) 8 weeks) while waiting for counts to recover
An eligible HLA-identical donor (either related or unrelated) should be available; in sibling donors, low resolution HLA typing (A,B,DR) will be considered sufficient; in the case of unrelated donors, high-resolution class I and II typing (A, B, C, DRB1 and DQ) should be matched at all 10 loci; donors must be willing and able to undergo peripheral blood progenitor mobilization * HLA-identical sibling (6/6): the donor must be determined to be an HLA-identical sibling (6/6) by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1)* Matched unrelated donor (10/10): high resolution molecular typing at the following loci is required: HLA-A, -B, -C, -DRBL, and �DQB1* NOTE: for matched donors � will allow select 1 antigen mismatched sibling donors and unrelated donors in accordance with site institutional standard, as long as matched at HLA-A, HLA-B, HLA-C, and DRB1, and with advanced discussion/approval by the Study Chair and the bone marrow transplant (BMT) co-chair
Patients must be considered reliable enough to comply with the medication regimen and follow-up, and have social support necessary to allow this compliance
Diffusion capacity of the lung for carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease
No known hypersensitivity to Escherichia (E.) coli-derived products
Patients in the measureable disease cohort must have at least one �target lesion� to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as �non-target� lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Platelet greater than or equal to 100,000/mcl
No signs of clinically significant hearing loss
Patients must have pulmonary function sufficient to receive bleomycin, with normal lung expansion, absence of crackles on auscultation, and normal carbon monoxide diffusion (DLCO), defined as greater than 80% predicted
Patients with a history of hypersensitivity reactions to prior chemotherapy administered for previous cancer diagnoses are eligible to participate in the study, unless the hypersensitivity reaction consisted of anaphylaxis not amenable to desensitization
Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator can consult the study chair or study co-chairs for uncertainty in this regard
Patients must be newly diagnosed with histologically confirmed intracranial ependymoma; patients with classic ependymoma (WHO II) or anaplastic ependymoma (WHO III) are eligible, as are various subtypes described as clear cell, papillary, cellular or a combination of the above
There is no minimum performance level; children with ependymoma may suffer neurologic sequelae as a result of their tumor or surgical measures taken to establish a diagnosis and resect the tumor; in the majority of cases, there is neurologic recovery; neurologic recovery is not likely to be impeded by protocol therapy
Patients with evidence of metastatic disease will be excluded; any evidence of non-contiguous spread beyond the primary site as determined by pre or post-operative magnetic resonance (MR) imaging of brain, pre or post-operative MR imaging of the spine, and post-operative cerebrospinal fluid (CSF) cytology obtained from the lumbar CSF space (the requirement for lumbar CSF examination may be waived if deemed to be medically contraindicated); CSF cytology from a ventriculostomy or permanent ventriculoperitoneal (VP) shunt that reveals the presence of tumor cells is indicative of metastatic disease
Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma are NOT eligible
No prior treatment other than surgical intervention and corticosteroids; patients are allowed to have had more than one attempt at resection prior to enrollment
Histologically documented Hodgkin lymphoma subclassified according to the World Health Organization (WHO) modification of the Rye Classification and staged according to the modified Ann Arbor Staging Classification system; patients must have clinical stage IA, IB, IIA or IIB; patients with �E� extensions will be eligible if all other criteria have been met; nodular lymphocyte predominant Hodgkin lymphoma is excluded
Patients must have a mediastinal mass > 0.33 maximum intrathoracic diameter on standing posterior-anterior chest x-ray or mass measuring > 10 cm in its largest diameter
No �currently active� second malignancy other than non-melanoma skin cancers; patients are not considered to have a �currently active� malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse
Patients may have had one cycle only of ABVD prior to enrolling on study; no other prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma is allowed; if patient has had one cycle of ABVD, in order to be eligible to enroll on Cancer and Leukemia Group B (CALGB) 50801, the patient must have had all of the following tests prior to starting the first cycle of ABVD:* Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multi gated acquisition (MUGA)* Pulmonary function tests (PFTs) (including diffusing capacity of the lung for carbon monoxide [DLCO]/forced vital capacity [FVC])* CT scan (neck**, chest, abdomen, pelvis)* FDG-PET/CT scan* Chest X-ray, posterior-anterior (PA) & lateral* Complete blood count (CBC), differential, platelets* Erythrocyte sedimentation rate (ESR)* Serum creatinine* Glucose* Aspartate aminotransferase (AST)* Alkaline phosphatase* Bilirubin* Lactate dehydrogenase (LDH)** Patients with a negative FDG-PET/CT scan do not need to have had a dedicated neck CT scan prior to starting the previous cycle of ABVD
LVEF by ECHO or MUGA within institutional normal limits unless thought to be disease related; DLCO >= 60% with no symptomatic pulmonary disease unless thought to be disease related
Patients with the following characteristics (depth of stromal invasion and lymphovascular space involvement to be pathologically confirmed):            * Positive capillary-lymphovascular space involvement and one of the following:                ** Deep third penetration** Middle third penetration, clinical tumor >= 2 cm** Superficial third penetration, clinical tumor >= 5 cm* Negative capillary-lymphatic space involvement                ** Middle or deep third penetration, clinical tumor >= 4 cm
Alkaline phosphate =< 3 x normal
Patients who have met the pre-entry requirements
Patients with tumor in the parametria, pelvic lymph nodes or any other extra uterine site or with positive surgical margins
Patients with intestinal obstruction or gastrointestinal bleeding
Patients with renal abnormalities requiring modification of radiation field (pelvic kidney, renal transplant, etc.)
Must be able to read, write and understand English
Must have a diagnosis of head/neck cancer
Must have anatomically intact parotid glands and at least one submandibular gland; a focused (head/neck) history and exam conducted by a physician or dentist within the past year is required
Have never had acupuncture for xerostomia
History of xerostomia, Sjogren�s disease or other illness known to affect salivation prior to head/neck radiation
Suspected or known closure of salivary gland ducts on either side
Currently receiving or planning to receive other xerostomia treatment, including drugs, herbs or devices; all other treatments known to affect salivation should be stopped at least 14 days prior to enrollment
Patients with all degrees of renal dysfunction are allowed including patients on hemodialysis; patients with mild to severe hepatic dysfunction are allowed as defined below:
For patients with a recently placed biliary stent, patients should have consistent results within a hepatic group from two laboratory readings within 3 days apart, taken at least 10 days following biliary stent placement; for patients with a biliary stent placed over 2 months ago, no obstruction or blockage can have occurred within the last 2 months
Evidence of bleeding diathesis
Patients with both hepatic and renal dysfunction will also be excluded
Histological confirmation of a high-grade malignant glioma is required; histologic diagnoses include, but are not limited to, anaplastic astrocytoma and glioblastoma multiforme; patients with DIPG are exempt from histologic verification if they have typical MRI findings of DIPG (i.e. hypo- or isointense on T1-weighted imaging, hyperintense on fluid-attenuated inversion recovery [FLAIR] or T2-weighted imaging, epicenter in the pons, > 50% of pons involved) in the face of a typical clinical presentation
Inoperable tumor or residual disease after resection
No overt renal, hepatic, cardiac or pulmonary disease
Newly diagnosed patients may need to be on steroids due to surgery or control of neurologic symptoms; patients on steroids postoperatively or for control of tumor-related edema are eligible, but attempts to keep patients on the lowest dose necessary to control symptoms should be made
Assignment of DPA to a family member or guardian should be offered to all patients 18 years of age or older
Patients with an HGG that was completely resected with good margins
Patients with a known coagulation disorder are excluded; patients with a first-degree relative with a history of venous thrombosis before age 50 years (yrs) or an arterial thrombosis before age 40 yrs must have the following testing performed prior to enrollment to exclude a heritable disorder; patients with a suspected disorder will be excluded
Patients who have had a thromboembolic event that is not line-related are excluded
Patients with known hypersensitivity to anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis or malignant cells identified on cerebrospinal fluid [CSF] cytology) are excluded
Patients must have pulmonary function tests (PFTs) including forced expiratory volume in 1 second (FEV1) within 84 days prior to registration; for FEV1, the best value obtained pre- or post-bronchodilator must be >= 1.2 liters/second and/or >= 50% predicted
Patients must not have more than 10% weight loss in the past 6 months
Patients must not have a history of seizures
Parent/legal guardian and child > 7 years old able to read English or Spanish
Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for valid test administration and cooperation with examinations
Availability of a reliable parent or legal guardian who is willing and able to complete all of the outcome measures and fulfill the requirements of the study, including administration of medications and accompanying the participant to all study visits
Signed Health Insurance Portability and Accountability Act (HIPAA) compliant research authorization
Inability to perform the testing procedure (for example, because of aphasia, motor deficits affecting the dominant hand, or intelligence quotient [IQ] < 70)
Known cardiac disorders including arrhythmias, hypertension requiring treatment or structural heart disease
History of stroke or head injury associated with loss of consciousness within 12 months of registration
Treatment with other stimulant medications within 14 days of registration; however, a diagnosis of attention-deficit hyperactivity disorder (ADHD) does NOT exclude a child from participation
Participants with known hypersensitivity to modafinil, armodafinil, or any of its components
Patients must have newly diagnosed National Cancer Institute (NCI) Standard Risk B-ALL or B-LLy Murphy stages I or II; patients with Down syndrome are also eligible* Note: for B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted
B-ALL patients with testicular leukemia are not eligible for AALL0932
Patient eligibility will be based on a diagnosis of Ewing sarcoma or PNET by institutional pathologist
Patients whose tumors arise in the dural and intra-dural soft tissues of the cranium and spine are not eligible
Patients with pathologic diagnoses other than Ewing sarcoma will be excluded
Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes) invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2 status; estrogen and progesterone receptor positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as either estrogen receptor (ER) or progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single probe or HER-2/CEP ration < 2.0 with an average copy number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2 equivocal is not eligible
Patients will have undergone axillary staging by sentinel node biopsy or axillary lymph nodes dissection (ALND); patients must have at least one, but no more than three known positive lymph nodes (pN1a, pN1b or pN1c); patients with micrometastases as the only nodal involvement (pN1mi) are not eligible; patients with positive sentinel node are not required to undergo full axillary lymph node dissection; this is at the discretion of the treating physician; axillary node evaluation is to be performed per the standard of care at each institution
Registration of patients who have not yet undergone Oncotype DX screening must occur no later than 56 days after definitive surgery; (for all patients, Step 2 Registration must occur within 84 days after definitive surgery); if the Oncotype DX Breast Cancer Assay has not been performed, patients must be willing to submit tissue samples for testing to determine the Recurrence Score value; a representative block or unstained sections from the representative block are sent directly to Genomic Health for Oncotype DX Breast Cancer Assay which will be performed according to the standard commercial process* If the Oncotype DX Recurrence Score is already known and is 25 or less, the patient must be registered to Step 2 immediately following Step 1 registration; if the Oncotype DX Recurrence Score is already known and is greater than 25, the patient is ineligible
Patients must not have received an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to registration
The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12; patients who consented to QOL prior to 12/1/12 should continue to complete QOL forms per their expectation report; patients who are able to complete a questionnaire in English must be offered the opportunity to participate in the Quality of Life and Economic Substudy; (The Quality of Life and Economic Substudy is available to U.S. INSTITUTIONS ONLY); patients who are not able to complete a questionnaire in English are registered to S1007 without participating in the Quality of Life and Economic Substudy* Patients who consent to participate in the Quality of Life and Economic Substudy and who do not yet know the results of their Oncotype DX screening must agree to complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment between 14 days prior to and 7 days after Step 1 Registration* Patients who consent to participate in the Quality of Life and Economic Substudy and who do already know their Oncotype DX Recurrence Score (and it is 25 or less) will proceed to Step 2 Registration without completing the S1007 Health-Related Quality of Life Questionnaire Enrollment Form (but will complete the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form)
Recurrence score (RS) by Oncotype DX must be =< 25
Patients randomized to either arm may also co-enroll in phase III trials that compare local therapies, or compare systemic therapies (such as chemotherapy, if randomized to Arm I of S1007)
The Quality of Life and Economic Substudy is permanently closed to accrual effective 12/1/12; patients at U.S. INSTITUTIONS who consent to participate in the Quality of Life and Economic Substudy must agree to complete the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form after Recurrence Score results and randomized treatment status are known but before treatment has been initiated
Patients receiving the initial course of chemotherapy including * Paclitaxel 135 mg/M2 IV over 3 hours on day 1 and * Cisplatin 75 mg/M2 IP on day 2  OR  * Paclitaxel 80 mg/m2 IV days 1, 8 and 15 and * Carboplatin AUC 6 IP on day 1
Patients who are able to read, understand and write English; if FLIE which has been translated into other languages, and validated, becomes available, then patients speaking these languages can be enrolled if translation of the symptom diary can be arranged dependent on availability of suitable translators
Patients who are able to complete the assessments
Patients must have met pre-entry requirements
Patients who are known to be hypersensitive to aprepitant, granisetron or any of the components of the patch or to dexamethasone
Patients who are pregnant or nursing; to date, no fetal studies in animals or humans have been performed; the possibility of harm to a fetus is likely
Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; examples of this would be hearing loss or neuropathy which would prevent tolerance to cisplatin, and paclitaxel administration; the investigator should feel free to consult the Study Chair or Study Co-Chairs for uncertainty in this regard
Patients who, in the opinion of the treating physician, have a medical condition, or currently take medications, which are felt to contraindicate safe or effective administration of the standard three drug anti-emetic regimen used in this study
Patients must have biopsy-proven de-novo diffuse large B-cell lymphoma (DLBCL) * Patients with primary mediastinal lymphoma or testicular lymphoma are not eligible* Patients with prior or simultaneous diagnosis of indolent lymphoma are not eligible* Post-transplant lymphoproliferative disorder with DLBCL morphology is ineligible
Patients must have a diagnostic quality contrast-enhanced CT scan of the chest, abdomen, and pelvis AND baseline FDG-PET scan performed within 28 days prior to registration* Low-resolution localization CT scans performed as part of a combined PET/CT scan are not adequate for enrollment or response determination on this protocol* If a patient has an allergy to CT contrast, then a non-enhanced CT will be acceptable
Patients must be offered the opportunity to consent to the use of specimens for future research
The lymphoma must express the cluster of differentiation (CD)20 antigen by either flow cytometry using anti-CD20 antibodies or by immunoperoxidase staining of paraffin sections; a report providing confirmation of CD20 expression must be submitted
The following tests must be performed within 42 days prior to registration either for diagnosis/staging or to obtain baseline values:* White blood cells (WBC)* Hemoglobin* Lactate dehydrogenase (LDH)* Hepatitis B-surface antigen (Ag) and anti-core antibody (Ab)
Patients must have completed 3 cycles of R-CHOP with no evidence of disease progression
Interim PET/CT scans must have been submitted for centralized review
If PET-negative based on the returned results from centralized review, patients must be planning to begin further treatment within 35 days of the start of cycle 3 of R-CHOP; if PET-positive based on the returned results from centralized review, it is important for patients to start IFRT as soon as possible after the end of cycle 3 of R-CHOP; they should be planning to initiate IFRT followed by yttrium-90 ibritumomab tiuxetan within 35 days of the start of cycle 3 of R-CHOP
Pathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate- to high-risk for recurrence as determined by one of the following combinations:             * Gleason score 7-10 + T1c-T2b (palpation) + prostate-specific antigen (PSA) < 50 ng/mL (includes intermediate- and high-risk patients)* Gleason score 6 + T2c-T4 (palpation) + PSA < 50 ng/mL OR Gleason score 6 + >= 50% (positive) biopsies + PSA < 50 ng/ml* Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL* Patients previously diagnosed with low risk prostate cancer undergoing active surveillance who are re-biopsied and found to have unfavorable intermediate risk disease or favorable high risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedure
Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal computed tomography [CT] or magnetic resonance [MR]), (but not by nodal sampling, or dissection) within 90 days prior to registration            * Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1.5 cm
Baseline serum PSA value performed with a Food and Drug Administration (FDA)-approved assay (e.g., Abbott, Hybritech) within 120 days prior to registration
Study entry PSA should not be obtained during the following time frames:             * 10-day period following prostate biopsy* Following initiation of hormonal therapy* Within 30 days after discontinuation of finasteride* Within 90 days after discontinuation of dutasteride
Previous pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy
Previous hormonal therapy, such as LHRH agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., diethylstilbestrol [DES]), or surgical castration (orchiectomy)
Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both LHRH agonist and oral anti-androgen) is =< 45 days prior to the date of registration
Use of finasteride within 30 days prior to registration
Use of dutasteride or dutasteride/tamsulosin (Jalyn) within 90 days prior to registration
Prior allergic reaction to the hormones involved in this protocol
Patients status post a negative lymph node dissection are not eligible
Patients enrolling in the BRCA-deficient cohorts must have a documented BRCA1 or BRCA2 germline mutation; alternatively, patients with tumors harboring somatic BRCA mutations may also enroll after discussion with the principal investigator
Any patient requiring chronic maintenance of white blood cell counts or granulocyte counts through the use of growth factor support (e.g. Neulasta, Neupogen)
Patients with other medical conditions judged by the investigator to be clinically relevant in the setting of this study, which may include active infectious processes, intractable emesis, or chronic diarrheal disease
Subjects with a known allergy to lidocaine
Cytological or histological confirmed diagnosis of advanced hepatocellular or renal cell carcinoma; HCC patients should not be amenable to treatment with surgery or to orthotopic liver transplant (Phase I)
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
HCC patients only: Cancer potentially amenable to local modalities of therapy or surgical resection (phase I)
Known or suspected allergy or hypersensitivity to any component of TH-302, sorafenib, or any of the sorafenib excipients
Any condition that severely impairs patient�s ability to swallow whole pills
Receiving any medication that has documented data or is generally accepted as having increased risk of QT prolongation and/or Torsades de Pointes
Fibrolamellar histology HCC, mixed hepatocholangiocarcinoma, hepatic sarcomas and other non-HCC primary liver tumors
History of lobectomy involving > 50% of lobe
Radioembolization within 8 weeks of day 1 dosing of sorafenib
Child Pugh class A or B7 liver disease
Ability to receive intravenous contrast for the purpose of imaging
Cancer potentially amenable to local modalities of therapy or surgical resection
Diagnosis of ALL, in first remission; enrollment on a Children Oncology Group (COG) therapeutic study for ALL is not required
Receiving continuous oral 6MP during the maintenance phase of therapy for ALL (held only for toxicity or illness), and will be returning to the clinic every 4 weeks for scheduled appointments while enrolled on COG ACCL1033 (between days 1 and 141)
Has a designated parent or caregiver who is willing to enter into a mutual agreement with the patient to participate in a daily supervised medication administration routine
Able and willing to use the MEMS� TrackCap� (e.g., not using a pillbox or prescribed liquid 6MP)
Parent/caregiver and patient (if 12 years and older) must be willing to use a cellular telephone to receive medication reminders via text messaging during study period
Patient and parent/caregiver must speak English or Spanish
Patients who previously participated in or are currently participating in another intervention clinical trial designed to improve adherence
Patient must be newly diagnosed or relapsed/progressed with a brain tumor that has not previously been treated with CRT* Note: COG therapeutic study participation is not required for ACCL10P1 enrollment
Patient enrollment must occur within 4 calendar months following completion of CRT* Reminder: after patient enrollment, baseline testing followed by randomization must occur within 2-4 months after completion of CRT
The patient must have an identified caregiver who is willing and able to oversee the training practice during the intervention period (ie, for 5-9 weeks starting approximately 3 months after completion of CRT)
The patient must have access to a telephone and phone number where they can be reached
The patient and caregiver must have reading, speaking and listening comprehension of English
Patients with pontine glioma are not eligible
Patients with an estimated survival of less than one year are not eligible
Patients with a history of traumatic brain injury prior to tumor diagnosis are not eligible
Patients with a motor, visual, or auditory handicap that prevents computer use (e.g., unresolved posterior fossa syndrome) are not eligible to participate in this trial
Patients with full-scale intelligence quotient (IQ) < 70 per previous testing OR existing diagnosis of/educational classification as a student with an intellectual disability are not eligible
Diagnosis of rectal adenocarcinoma
For this patient, the standard treatment recommendation in the absence of a clinical trial would be combined modality, neoadjuvant chemoradiation followed by curative intent surgical resection
Candidate for sphincter-sparing surgical resection prior to initiation of neoadjuvant therapy according to the primary surgeon
Clinical stage: T2N1, T3N0, T3N1* N2 disease is to be estimated as four or more lymph nodes that are >= 10 mm* Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, computed tomography (CT) or positron emission tomography (PET)/CT scan of the chest/abdomen/pelvis and either a pelvic magnetic resonance imaging (MRI) or an ultrasound (endorectal ultrasound [ERUS]); if a pelvic MRI is performed, it is acceptable to perform CT of the chest/abdomen, omitting CT imaging of the pelvis
Clinical T4 tumors
Primary surgeon indicates need for abdominoperineal (APR) at baseline
Evidence that tumor is adherent to or invading the mesorectal fascia on imaging studies such that the surgeon would not be able to perform an R0 resection (one with negative margins)
Co-morbid illnesses or other concurrent disease which, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Men are excluded from this study
cN0 or cN1 disease
Ability to complete questionnaire(s) by themselves or with assistance
Largest single focus of disease > 5 centimeters by either mammogram or MRI or both; Note: measurement of the largest single focus should include any satellite lesions within 1 centimeter of the index lesion
Surgical axillary staging procedure prior to first definitive breast operation; Note: fine-needle aspiration (FNA) or core needle biopsy of axillary node is permitted
cNX, cN2, or cN3 disease
Breast implants at time of diagnosis; Note: patients who have had implants previously removed prior to diagnosis are eligible
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would interfere significantly with whole-breast irradiation (such as connective tissue disorders, lupus, or scleroderma)
Patients with known breast cancer (BRCA) mutations; patients who are not tested or whose testing result is not returned at the time of registration are not excluded from registering to this study
Receiving anastrozole (1 mg) or letrozole (2.5 mg) orally once a day, for >= 21 days prior to registration and plan to continue throughout the duration of study
Body mass index (BMI) between 18 and 35 kg/m^2
Must have BOTH estrogen receptor (ER) and progesterone receptor (PR)-positive tumors and BOTH must be >= 26% positive; alternatively, if ER and PR are determined by Allred score, the score needs to be 5 or higher
Women who are postmenopausal by surgery, radiotherapy, or presence of natural amenorrhea >= 12 months
>= 5/10 arthralgia (in hands, wrist, knees, or hips) while being treated with anastrozole or letrozole which is felt by the patient to be caused by their aromatase inhibitor, as measured by verbally addressing the following question: please rate your pain by picking a number, from 0 to 10 (0 being none and 10 being as bad as you can imagine) that best describes your pain from your aromatase inhibitor breast cancer medication on AVERAGE, over the past week* Note: Patients may, or may not, be taking non-opioid analgesics
Ability to complete questionnaire(s) by themselves or with assistance
Willing to provide blood samples for correlative research purposes
Laboratory values obtained =< 365* days prior to registration:* Note: Without medical situations that should change these parameters since they were done
Known hypersensitivity to any component of testosterone
History of a deep venous thrombosis or a thromboembolism
Current or planned use of cyclosporine, anticoagulants, insulin, oral or injectable vitamin D doses over 4,000 IU/day, or tamoxifen
Patients receiving histone deacetylase (HDAC) inhibitors or compounds with HDAC inhibitor like activity, such as valproic acid, are ineligible; patients who have received such agents may enroll on this study after a 14-day washout period
Patients with cytologically or histologically confirmed locally advanced or metastatic pancreas adenocarcinoma with a BRCA1 or 2 or PALB2 mutation confirmed by report from Myriad Genetics (United States of America [USA]); reports from other molecular diagnostic companies can be used to confirm mutations as well; BRCA 1 or 2 or PALB2 mutation can be confirmed locally for all international sites* For Part I, non-randomized, lead-in portion, patients with a known BRCA 1 or 2 or PALB2 mutation are eligible along with patients who potentially may have a likelihood of having a BRCA mutation (e.g., personal or family history of breast, pancreas, ovary, endometrial, prostate or other likely related malignancy); for Part I, randomized portion, a known BRCA 1 or 2 or PALB2 mutation is required
For Part I: patients with known contraindications to platinum agents are excluded
Patients with prior malignancy successfully treated who are currently stable and on no active treatment are eligible
Patients with biliary obstruction for which a stent has been placed are eligible, provided the shunt has been in place for at least 10 days prior to the first dose of romidepsin and the liver function has stabilized; two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function; there should be no evidence of biliary sepsis
Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of romidepsin will be determined following review of their case by the site principal investigator* Patients treated with any of the medications prohibited must discontinue their use at least 7 days prior to the first dose of romidepsin; certain other agents that interact with the CYP3A4 system may be used with caution
Patients with prostate cancer, renal cell cancer, neuroendocrine tumors, lung cancer, colorectal cancers, soft tissue sarcomas, glioma, and thyroid cancer are excluded in the normal and mild cohorts due to a lack of efficacy in these tumor types in phase 2 studies; patients with prostate cancer, renal cell cancer, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are allowed to enroll in the moderate and severe cohorts only; patients with neuroendocrine tumors are still excluded from the moderate and severe cohorts
Thiazolidinedione agents such as rosiglitazone and pioglitazone are not permitted
Warfarin is not permitted
Biopsy-proven, systemic DLBCL with a proliferation rate =< 90%, that has been confirmed by an acquired immune deficiency syndrome (AIDS) Malignancy Clinical Trial Consortium (AMC)-approved site pathologist using hematoxylin and eosin (H&E) and immunohistochemical stains; if a hard copy of the pathology report is unavailable at the time of enrollment into the screening segment, a verbal report by the pathologist confirming the diagnosis must be documented in the medical chart; a hardcopy of the pathology report must be available prior to randomization (enrollment into the Treatment Segment); Note: measurable disease is not an entry requirement
Pathology slides from tumor tissue obtained by surgical excision or core biopsy must be reviewed by the designated site pathologist, or backup pathologist, prior to study entry; confirmation of the diagnosis must be documented by the AMC-approved pathologist prior to study entry; please reference the AMC-068 Manual of Procedures (MOP) for further instructions on documenting the diagnosis; the site pathologist for non-Hodgkin lymphoma (NHL) must be approved through the AMC's external quality assurance (EQA) process
Participants must have a lumbar puncture with negative cerebral spinal fluid cytology within 4 weeks prior to enrollment
All participants must be prescribed combination antiretroviral therapy with the goal of virological suppression using an acceptable regimen that adheres to national guidelines for treatment of HIV infection; non-suppressed, treatment experienced patients, defined as patients with a viral load > 400 copies/mL who have been on antiretroviral therapy for more than 4 months can be enrolled if an alternative antiretroviral therapy (ART) regimen is available that includes at least two ART drugs that, in the opinion of the site investigator, are expected to have activity based on genotypic testing (if available) and treatment history; patients are not allowed to receive zidovudine (azidothymidine [AZT]) as part of concurrent chemotherapy and ART regimen, since it is myelosuppressive; zidovudine may be discontinued and substituted as clinically indicated prior to or at the time of enrollment
Participants must, in the opinion of the investigator, be capable of complying with the protocol
Participants must have a CD4 count performed within 30 days of enrollment
Participants with active infection(s) for which they are receiving drug treatment unless the clinical status is judged to be stable and survival is estimated to be at least 6 weeks
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen, or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
The following agents are not permitted while patients are taking MLN8237, and should be discontinued at prior to registration if patients are taking them:* Patients must stop using the proton pump inhibitor (PPI) for at least 4 days prior to the first dose of MLN8237; administration of PPI while on study is not permitted* Histamine-2 (H2) receptor antagonists are not permitted from the day prior through to the end of MLN8237 dosing, except as required for premedication for rituximab; constant dosing of H2 blockers is not permitted* Antacid preparations are not permitted for 2 hours before or 2 hours after administration of MLN8237* Administration of pancreatic enzymes is not permitted at any time while on study* Co-administration of enzyme-inducing antiepileptic drugs, rifampin, rifabutin, rifapentine or St. John's wort is not permitted* Concurrent bisphosphonate therapy is allowed if it was started before study entry and is maintained at recommended dosing intervals; if bisphosphonate therapy is initiated after study entry, bone lesions will not be considered evaluable for disease response* Patients must be willing not drive, operate dangerous tools or machinery, or engage in any other potentially hazardous activity that requires full alertness and coordination if they experience excessive sedation; if a patient experiences excessive sedation believed to be related to MLN8237, treatment with MLN8237 should be interrupted* Patients must be willing to limit alcohol consumption to no more than 1 standard unit of alcohol (12 oz beer [350 mL], 1.5 oz [45 mL] of 80-proof alcohol, or one 6-oz [175 mL] glass of wine) per day during the study and for 30 days from the last dose of MLN8237; minimize the use of agents with central nervous system (CNS) effects* Benzodiazepine use is discouraged but not prohibited
Patients with T2 or T3 primary tumors (N0-3, M0) not amenable to surgical resection by standard radical vulvectomy
Patients judged capable of tolerating a radical course of chemoradiation therapy
Patients with recurrent carcinoma of the vulva regardless of previous treatment
Patients with vulvar melanomas or sarcomas
Patients must be newly diagnosed with localized primary CNS NGGCT (Stratum 1) or localized primary CNS germinoma (Stratum 2); germ cell tumors located in the suprasellar, pineal, bifocal (pineal + suprasellar) and ventricles are eligible; tumors present in the above mentioned locations and with unifocal parenchymal extension are eligible* Stratum 1(NGGCT): Patients must have one of the following criteria:** Patients with serum and/or CSF hCGbeta > 100 mIU/mL or any elevation of serum and/or CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the institutional normal are eligible, irrespective of biopsy results** Patients with any of the following elements on biopsy/resection are eligible, irrespective of serum and/or CSF hCGbeta and AFP levels: endodermal sinus tumor (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma, and mixed GCT with malignant GCT elements* Stratum 2 (Germinoma): Patients must have both serum and CSF markers obtained (unless obtaining CSF is medically contraindicated) and must have one of the following criteria to be eligible:** Patients with institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) AND hCGbeta 5 to =< 50 mIU/mL in serum and/or CSF (unless medically contraindicated) (only 1 is required to be elevated) are eligible; no histologic confirmation required** Patients with bifocal (pineal + suprasellar) involvement or pineal lesion with diabetes insipidus (D1) AND hCGbeta =< 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible; no histologic confirmation required** Patients with histologically confirmed germinoma or germinoma mixed with mature teratoma and hCGbeta =< 100 mIU/mL in serum and/or CSF and institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible
All patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment; if surgical resection is performed, patients must have pre-operative and post-operative cranial MRI with and without gadolinium; the post-operative brain MRI should be obtained within 72 hours of surgery; if patient has a biopsy only, post-operative cranial MRI is recommended but not required; all patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment; Note: if the spine study is performed for the first time after surgical resection or biopsy, it is recommended to be obtained with and without gadolinium
Patients must have CSF tumor markers obtained prior to enrollment unless medically contraindicated; ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred; in case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123; patients must be enrolled within 31 days of definitive diagnostic surgery (day 0) or clinical diagnosis
Patients must not be in status, coma, or assisted ventilation prior to study enrollment
Patients with mature teratoma or completely resected immature teratoma with normal tumor markers are not eligible
Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not eligible
HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization [FISH] or silver in situ hybridization [SISH] >= 2.0)
Prior WBRT
Leptomeningeal disease
All patients must have undergone a cone biopsy or loop electrosurgical excision procedure (LEEP); depth of invasion must be =< 10 mm
Patients must have no evidence of metastasis on positron emission tomography (PET) scan or magnetic resonance imaging (MRI) or computed tomography (CT) scan of the pelvis and chest imaging
Patients who have met the pre-entry requirements
Patients with clear cell or neuroendocrine cell types
Patients with depth of invasion > 10 mm on first cone biopsy (or LEEP)
Patients must have a histologically confirmed diagnosis of invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2, for whom standard adjuvant endocrine therapy is planned; estrogen and progesterone receptor positivity must be assessed according to American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guidelines as either estrogen receptor (ER) or progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result negativity must be assessed as per ASCO/CAP 2013 guidelines using immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number < 4.0 signals per cell by single probe or HER-2/chromosome enumeration probe [CEP] ratio < 2.0 with an average copy number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene amplification (ISH) must be performed and the ISH must be negative; ISH is not required if IHC is 0 or 1+; HER-2 equivocal is not eligible
Patients must have undergone axillary staging by sentinel node biopsy or axillary lymph node dissection (ALND)* For patients with 1-3 positive lymph nodes, sentinel node biopsy alone is allowed provided that the patient completed either whole breast or chest wall radiation and the primary tumor is < 5 cm* All patients with >= 4 positive lymph nodes must have completed ALND (with or without prior sentinel node biopsy)
Patients must not be receiving or planning to receive trastuzumab; concurrent bisphosphonate therapy is allowed; patients must not have prior exposure to mechanistic target of rapamycin (serine/threonine kinase) (mTOR) inhibitors (rapamycin, everolimus, temsirolimus, deforolimus); patients must not have prior treatment with any investigational drug within the preceding 28 days and must not be planning to receive any other investigational drug for the duration of the study
Patients previously diagnosed with diabetes must not have uncontrolled diabetes (defined as a hemoglobin [Hg] A1C > 7% within 28 days prior to registration)
Patients (at National Cancer Institute [NCI] Community Oncology Research Program [NCORP] Institutions only) must be offered the opportunity to participate in the S1207-E01 Behavioral and Health Outcomes study (BAHO); NOTE: patients who have already started endocrine therapy are eligible for the BAHO study
For the Phase II portion only, patients must have high-risk MM based on one or more of the following criteria at the time of initial diagnosis (prior to any chemotherapy):* Poor-risk genomic signature according to the University of Arkansas 70-gene model (available clinically as myeloma prognostic risk score [MyPRS] score, Signal Genetics, Inc) AND/OR* Translocation (14;16), and/or translocation (14;20), and/or deletion (17p) by fluorescence in-situ hybridization (FISH) or cytogenetics AND/OR* Primary plasma cell leukemia (defined by either >= 2,000 plasma cells/mL of peripheral blood, or 20% on a manual differential count) AND/OR* Serum lactate dehydrogenase (LDH) >= 2 x institutional upper limit of normal (IULN) AND/OR* 1q21 amplification by FISH analysis AND/OR* High risk by the SKY92 signature* All tests for establishing high risk status must be completed within 28 days prior to registration for patients with no prior therapy, or within 28 days prior to initiation of first Induction course for patients with prior therapy
Patients with non-secretory MM or known amyloidosis are not eligible
Patients must have baseline skeletal survey (whole body x-ray) to document lytic lesions, osteopenia or compression fracture
Patients must not have POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Uncontrolled diabetes: a glycated hemoglobin (Hg A1C) > 7% within 14 days prior to registration; the same criterion will be used in patients with confirmed diagnosis of diabetes mellitus who have been on a stable dietary or therapeutic regimen for this condition in the last three months
Patients must not have any psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
Patients must be registered to the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS)� program and must be willing and able to comply with the requirements of the Revlimid REMS� program
Patients must have high-risk neuroblastoma
Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below):* Bone disease** At least one metaiodobenzylguanidine (MIBG) avid bone site or diffuse MIBG uptake*** For recurrent/progressive or refractory disease a biopsy is not required regardless of number of MIBG avid lesions*** For persistent disease, if patient has only 1 or 2 MIBG avid lesions OR a Curie score of 1-2, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one site present at the time of enrollment (bone marrow, bone, or soft tissue) is required to be obtained at any time point prior to enrollment and two weeks subsequent to most recent prior therapy; if a patient has 3 or more MIBG avid lesions OR a Curie score of >= 3 then no biopsy is required for eligibility** If a tumor is known to be MIBG non-avid, then a patient must have at least one fludeoxyglucose (FDG)-positron emission tomography (PET) avid bone site present at the time of enrollment with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma obtained at any time prior to enrollment and two weeks subsequent to most recent prior therapy* Any amount of neuroblastoma tumor cells in the bone marrow based on routine morphology (with or without immunocytochemistry) in at least one sample from bilateral aspirates and biopsies* At least one soft tissue lesion that meets the criteria for a TARGET lesion as defined by:** SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter >= 10 mm, or for lymph nodes >= 15 mm on short axis; lesions meeting size criteria will be considered measurable** In addition to size, a lesion needs to meet ONE of the following criteria:*** MIBG avid; for patients with persistent disease only: if a patient has only 1 or 2 MIBG avid lesions OR a Curie score of 1-2, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one site present at time of enrollment (either bone marrow, bone and/or soft tissue) is required to be obtained at any time point prior to enrollment and at least two weeks subsequent to most recent prior therapy; if a patient has 3 or more MIBG avid lesions OR a Curie score of >= 3 then no biopsy is required for eligibility*** FDG-PET avid (only if tumor is known to be MIBG non-avid); these patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one FDG-PET avid site present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy*** Non-avid lesion (both MIBG and FDG-PET non-avid); these patients must have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma in at least one non-avid lesion present at the time of enrollment done prior to enrollment and at least two weeks subsequent to the most recent prior therapy
Patients with prior progressive disease who do not meet criteria above, are eligible as long as they have not been off treatment for > 3 months prior to enrollment on NANT 2011-04
Absolute phagocyte count (APC = neutrophils and monocytes): >= 1000/mm^3
Sinusoidal obstruction syndrome (SOS) if present, must be stable or improving clinically
=< grade 2 hypercalcemia (applicable only for dose levels that include cis retinoic acid [RA])
Patients with other ongoing serious medical issues must be approved by the study chair prior to registration
Patients with a paraben allergy cannot take isotretinoin preparations containing this compound (i.e. Accutane, Sotret) but are eligible if they can take an alternate preparation without paraben; (applicable only for entry onto dose levels receiving isotretinoin)
Patients with a history of venous or arterial thrombosis personally before the age of 40 years unless associated with a central line
Patient declines participation in NANT 2004-05; unless the institution has been granted special exemption from mandatory enrollment on NANT 2004-05 by the NANT Operations Center
Diagnosed with glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma who are clinically stable and have completed radiation therapy (excluding stereotactic radiosurgery) > 21 days and =< 24 months prior to enrollment; NOTE: clinical stability will be defined as a stable or improved Karnofsky performance status (KPS) compared to the prior month
>= 6 score on the worst fatigue question of the BFI (Brief Fatigue Inventory, question 3); it is not required for the patient to complete the entire BFI to meet this criterion
Undergone surgery (gross total or subtotal resection) or biopsy and will have been treated with concurrent radiation therapy and chemotherapy as standard of care for glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma patients; Note: radiation must be completed, but chemotherapy is allowed; patients who are currently using Optune device will be eligible to participate in this trial
Ability to complete questionnaire(s) by themselves or with assistance
History of hypersensitivity to other psychostimulants
History of steroid psychosis
History of or currently taking medications for attention deficit hyperactivity disorder, severe anxiety disorder, schizophrenia, or substance abuse by patient record and/or self-report
Currently using any other pharmacologic agents or nonpharmacologic interventions to specifically treat fatigue, including psychostimulants, antidepressants, acupuncture, etc. will be excluded; Note: antidepressants used to treat items other than fatigue (such as hot flashes or depression) are allowed if the patient has been on a stable dose for >= 30 days prior to registration and plans to continue for the duration of the trial; erythropoietin agents to treat anemia are allowed; exercise is allowed
Anticipating surgery, history of hypothyroidism, profound anemia (hemoglobin level of < 10 g/dL =< 28 days prior to registration), or clinical depression per physician discretion
History of or active glaucoma
Any of the following co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens:* History of myocardial infarction* Unstable angina* Left ventricular hypertrophy* Mitral valve prolapse syndrome
Patients must have either:* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (< 10% by immunohistochemistry [IHC] staining) and HER-2 negative breast cancer OR* ER negative/PR negative (< 10% by IHC staining) and HER-2 positive tumors* HER2 status will be determined per the 2013 American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines:** HER2 is considered positive if a) there is IHC 3+ staining or b) positive using either single probe in situ hybridization (ISH) or dual probe ISH** HER2 is considered negative if a) there is IHC 0 or 1+ staining or b) ISH negative using either single probe ISH or dual probe ISH* For patients enrolling after neoadjuvant therapy, the ER, PR, and HER2 markers are based on assessment prior to initiating neoadjuvant treatment
No patients with known deleterious mutations in breast cancer (BRCA) genes
No history of receiving endocrine therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures; these agents used previously as chemoprevention are allowed
No patients scheduled to receive partial breast irradiation following breast conserving surgery
Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):* No history of untreatable claustrophobia* No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)* No history of sickle cell disease* No contraindication to intravenous contrast administration* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance* No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) < 30mL/min/1.73 m^2 based on a serum creatinine level obtained within 28 days prior to registration* Weight lower than that allowable by the MRI table
No prior MRI of study breast within the 12 months prior to registration
Patients must have an HCC diagnosis (initial, recurrent, progressive and/or refractory to other therapies) by at least one criterion listed below =< 360 days prior to study entry* Pathologically (histologically or cytologically) proven diagnosis of HCC* At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, inferior vena cava [IVC] and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis* For patients whose CURRENT disease is vascular only: enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI, in a patient with known HCC (diagnosed previously < 720 days)
Patients must have measureable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measureable as per Response Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days PRIOR TO STUDY ENTRY
Appropriate for protocol entry based upon the following minimum diagnostic workup:* History/physical examination including examination for encephalopathy, ascites, weight, height, and blood pressure within 14 days prior to study entry* Assessment by radiation oncologist and medical oncologist or hepatologist who specializes in treatment of HCC within 28 days prior to study entry* Pre-randomization scan (REQUIRED for all patients): Within 28 days prior to study entry, CT scan chest/abdomen/pelvis or positron emission tomography (PET) CT chest/abdomen/pelvis with multiphasic liver CT or multiphasic liver magnetic resonance (MR) scan (MRI of abdomen and pelvis with contrast with CT chest) is permitted
Child-Pugh score A within 14 days prior to study entry
Unsuitable for resection or transplant or radiofrequency ablation (RFA)
Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al (2011):* Technical contraindications: arteriovenous fistula, including surgical portosystemic shunt or spontaneous portosystemic shunt* Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial invasion or bland portal vein occlusion* Medical contraindications including congestive heart failure, angina, severe peripheral vascular disease* Presence of extrahepatic disease* No response post TACE (or DEB) or progressive HCC despite TACE; prior TACE or DEB is allowed but must be > 28 days from study entry* Serious toxicity following prior TACE (or DEB); prior TACE or DEB must be > 28 days from study entry* Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g. combination of relative contraindications including age > 80 years, tumor > 10 cm, > 50% replacement of the liver by HCC, extensive multinodular bilobar HCC, biliary drainage)
Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
Maximal diameter of any one hepatocellular carcinoma > 15 cm
Total sum of maximum diameters of each definite parenchymal hepatocellular carcinomas within the liver or maximum diameter of a single conglomerate HCC > 20 cm
More than 5 discrete intrahepatic parenchymal foci of definite HCC
Direct tumor extension into the stomach, duodenum, small bowel or large bowel
Measureable common or main branch biliary duct involvement with HCC
Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
Patients with history of segmental resections are eligible (i.e. right colectomy, extended right colectomy, transverse colectomy, left colectomy, extended left colectomy, sigmoid colectomy, low anterior resection, abdominoperineal resection); the definition of resection does not include endomucosal resection (EMR); patients that have received total proctocolectomy are ineligible* In addition to segmental resections, the following types of procedures are allowed: polypectomy: for Tis (stage 0) or pT1 patients only, resection may consist entirely of polypectomy (without completion of partial colectomy) if ALL of the following criteria are met:** Single specimen, completely removed** Clear margins** None of the following must be present:*** Moderate or poor differentiation*** Lymphovascular invasion*** Perineural invasion* Transanal excision is allowed for pT1 rectal cancer patients with well or moderately differentiated tumors if National Comprehensive Cancer Network (NCCN) criteria for transanal excision are met, as stipulated here:** < 30% circumference of bowel** < 3 cm in size** Margin clear (> 3 mm)** Mobile, nonfixed** Within 8cm of anal verge** T1 only** Endoscopically removed polyp with cancer** No lymphovascular invasion or perineural invasion** Well to moderately differentiated** No evidence of lymphadenopathy on pretreatment imaging***When the lesion can be adequately identified in the rectum, transanal endoscopic microsurgery (TEM) may be used; TEM for more proximal lesions may be technically feasible
Patients must be registered between 180 days and 465 days (inclusive) of primary resection; patients must show no evidence of disease (NED) based on post-operative colonoscopy (performed at least 180 days after the colon resection date or at least 120 days after the rectal resection date and prior to registration) and computed tomography (CT) scans* of chest, abdomen and pelvis (performed at least 180 days after the colon resection date or at least 120 days after the rectal resection date and prior to registration); patients with adenomas detected at the one-year postoperative colonoscopy are eligible if all adenomas have been completely removed* CT scan is for high risk patients, as per National Comprehensive Cancer Network (NCCN) guidelines and at the discretion of the treating physician* NOTE: magnetic resonance imaging (MRI) evaluation is an acceptable alternative to CT scans for eligibility purposes
Patients must not have a known history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease
Patients must have a pure tone audiometry evaluation to document air conduction within 30 days prior to registration; patients with hearing loss > 40 dB in any of the five tested frequencies (250 Hertz [Hz], 500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz) are not eligible; patients with active ear infections should be tested only after the acute phase of infection has resolved; for optimal results, it is recommended that testing be conducted by an audiologist, in a hearing test room, with insert earphones; Note: sites should not order audiometry evaluation until the potential participant has met all other eligibility criteria required for this study
Patients must not have known hypersensitivity to eflornithine or sulindac or the excipients byproducts; patients must not have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other non-steroidal antiinflammatory drugs (NSAIDs)
Patients must not have documented history of gastric/duodenal ulcer within the last 12 months; participant must not currently be on treatment for gastric/duodenal ulcer or be experiencing symptoms at study entry; patients with gastroesophageal reflux disease (GERD) are eligible, however, and these patients may receive over-the-counter histamine-2 (H2) antagonists; proton-pump inhibitors, or other prescription-based treatment for GERD
Patients must have no significant medical or psychiatric condition that would preclude study completion; tests and exams for this determination should be completed within 28 days prior to registration
A total WBC >= 3.1 x 10^3/mcL is allowed for non-Hispanic black males (NHBM) and total WBC >= 3.4 x 10^3/mcL for non-Hispanic black females (NHBF) * Exception: If the WBC is lower than the above levels, the patient may be enrolled IF the absolute neutrophil count (ANC) is >= 1.3 for NHBM, >= 1.4 for NHBF, or >= 1.5 for all.
SPECIMEN SUBMISSION AND SUBSTUDY CRITERIA
Patients must be offered the option to participate in submission of specimens for banking for future translational medicine studies
Patients participating through PK sites, must be offered the option to submit blood specimens for population pharmacokinetic analysis
Patients must be offered the option to participate in the Diet and Lifestyle Substudy
REGULATORY CRITERIA
Individuals must not currently be participating in any other clinical trial for the treatment or prevention of cancer unless they are no longer receiving the intervention and are in the follow-up phase only; patients must also agree not to join such a trial while participating in this study
SITE INCLUSION CRITERIA:
Minimum provider participation requirements met; this includes participation in the study intervention of a minimum of the following: Site Coordinator and Site Clinician Investigator/study champion
Site Coordinator identification and contact with as many as possible of the site�s relevant healthcare providers and staff regarding participation in the study intervention; relevant providers may include physicians, nurse practitioners, physician assistants, patient navigators, nurses and other staff who interact directly with breast cancer patients
PATIENT INCLUSION CRITERIA:
Able to read and write in English or Spanish
SITE EXCLUSION CRITERIA:
On-site genetics professionals as defined by the Commission on Cancer
PATIENT EXCLUSION CRITERIA:
Received HBOC genetic counseling or mutation testing prior to diagnosis; if the patient was previously tested only for a variant of uncertain clinical significance (i.e., not for known familial mutation, Jewish ethnicity panel/multisite 3 or comprehensive sequencing) and documentation is provided, they remain eligible
The SunCoast Community Clinical Oncology Program (CCOP) Research Base does not exclude patients who are participating in other investigational studies; refer to the local Institutional Review Board (IRB) guidelines
STEP I: Prior systemic glucocorticoid use for the treatment of non-malignant disorders is permitted; prior or concurrent topical or localized glucocorticoid therapy to treat non-malignant comorbid disorders is permitted
STEP I: Patients with monoclonal gammopathy of undetermined significance or asymptomatic multiple myeloma are not eligible
STEP I: Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation
STEP I: Patient enrolling to this study must agree to register to the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
STEP II: Patients must have complete induction without experiencing progression or patients must have received at least 6 cycles on Arm A and 4 cycles on Arm B but stopped induction therapy due to adverse events
STEP II: Patient enrolling to this study must agree to register to the mandatory RevAssist program and be willing and able to comply with the requirements of RevAssist
Disease confined to the intraperitoneal and retroperitoneal cavity; Note: nodal disease below the diaphragm, implants adherent to the surface of the liver or intrahepatic lesions will not be exclusionary; patients remain eligible if all intrahepatic tumor is debulked or ablated by the time treatment is initiated
EXPANSION PHASE ONLY: Evaluable or measurable disease with the largest nodule measuring less than 5 cm in greatest dimension by radiographic imaging after debulking procedure
Known standard therapy for the patient�s disease that is potentially curative or definitely capable of extending life expectancy; note: patients with recurrent platinum-sensitive ovarian, primary peritoneal or fallopian tube will be allowed, if the investigator believes the study treatment is a better alternative to initiation platinum-based chemotherapy, such as patients with a prior platinum allergy or low volume disease for whom platinum-based therapy is deferred until a later date
Metastatic disease outside the intraperitoneal cavity and retroperitoneum, intrahepatic lesions, or pleural effusions; significant ascites precluding catheter placement; exception: intrahepatic lesions removed or planning to be removed during the debulking procedure
Female patients presenting with initial diagnosis of any type of cancer
Patients must not have had a prior hysterectomy, bilateral oophorectomy or sterilization of any method
Patients must be pre-menopausal patients within the reproductive age range
Please note, pre-menopausal will be defined as women meeting the following criteria:* Patients not currently on hormonal contraception with the presence of menses in the past 6 months* If no menstruation in the past 6 months, without hormonal manipulation, then confirmed follicle-stimulating hormone (FSH) < 23 mlU/mL* If age < 47 years and on hormonal contraception then patient will be eligible regardless of menstrual history* If age >= 47 years and on hormonal contraception then FSH confirmed < 23 mIU/mL
Patients must have the cognitive ability to participate in the study
Patients� melanoma must be positive for both tyrosinase and human leukocyte antigen (HLA)-A2 per Loyola University Medical Center pathologic review from fine needle aspiration (FNA)/core/excisional biopsy of lesion
Patients treated with prior Interleukin-2 will be allowed to be in this study
Special classes of subjects such as fetuses, pregnant women, children, prisoners, institutionalized individuals, or others who are likely to be vulnerable
Patients taking steroids for disease control or pain management
Patients that have undergone Tyrosinase immunotherapy
Known hypersensitivity to any of the components of the study drugs
Patients assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of cabozantinib will be determined following review of their cases by the principal investigator; patients who are taking enzyme-inducing anticonvulsant agents are not eligible
The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted (please note that there may be cases in which patients on study require anticoagulation for deep vein thrombosis [DVT]/pulmonary embolism [PE] management; this does not necessitate taking the patient off study)
The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment
Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days of entry on this study; seven days must have elapsed since administration of a short acting myeloid growth factor
Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma
Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of the anti-GD2 therapy are not eligible
Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible
Imaging evaluations necessary to establish eligibility for study entry must be done within three (3) weeks prior to registration
All other evaluations necessary to establish eligibility for study entry must be done within two (2) weeks prior to registration
All patients must meet the following inclusion and exclusion criteria; NO EXCEPTIONS WILL BE GIVEN
Participant is willing to sign a screening consent and provide pre-trial tumor material for BRAF testing (both for BRAF V^600E mutation and BRAF KIAA1549 fusion assessments)* All patients who are candidates for enrollment in stratum 5 based on their tumor histology must be pre-screened* Screening may be applied to potential stratum 1 and 2 patients
Patient must have one of the following: * For stratum 5: non NF-1 associated low grade glioma (LGG) (other than pilocytic astrocytoma or optic pathway glioma) * For stratum 1 or 2: non NF-1, non-optic pathway pilocytic astrocytoma; note: all patients with non NF-1 associated optic pathway glioma with or without tissue must be enrolled on stratum 4
Patients with histologically diagnosed progressive, recurrent or refractory non NF-1 associated LGG (other than pilocytic astrocytoma or optic pathway glioma); these patients must have BRAF aberrations as documented by the Lindeman and Ligon Labs at Brigham and Women�s Hospital using the same procedures
Patients must have bi-dimensionally measurable disease defined as at least one lesion that can be accurately measured in at least two planes in order to be eligible for this study
Radiation: patients must have:* Had their last fraction of local irradiation to primary tumor >= 12 months prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression* Had their last fraction of craniospinal irradiation (> 24 Gy) > 3 months prior to registration
Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at least 2 weeks for long-acting formulations
Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration
Patients with uncontrolled seizures
Patients must have recurrence or progression of their low-grade glioma after coming off treatment with AZD6244 on PBTC-029 or PBTC-029B, with or without having received additional anti-tumor therapy following discontinuation of AZD6244; the progression must be unequivocal and sufficient to warrant re-treatment in the opinion of the investigator; progression will be defined as either progressive disease (PD) that meets the study definitions of progressive disease by MRI or vision deterioration thought to be related to tumor in patients with optic pathway tumors
Patients must have received treatment on PBTC-029 or PBTC-029B for a minimum of 12 courses with at least stable disease, or had a sustained response (partial response [PR]/ complete response [CR]) but remained on treatment < 12 courses
Patients must have bi-dimensionally measureable disease defined as at least one lesion that can be accurately measured in at least two planes
Patient must have clinically T1-3, N1 breast cancer at the time of diagnosis (before neoadjuvant therapy); clinical axillary nodal involvement can be assessed by palpation, ultrasound, CT scan, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, or PET/CT scan
Patient must have had pathologic confirmation of axillary nodal involvement at presentation (before neoadjuvant therapy) based on either a positive fine needle aspirate (FNA) (demonstrating malignant cells) or positive core needle biopsy (demonstrating invasive adenocarcinoma); the FNA or core needle biopsy can be performed either by palpation or by image guidance; documentation of axillary nodal positivity by sentinel node biopsy (before neoadjuvant therapy) is not permitted
Patients must have had estrogen receptor (ER) analysis performed on the primary breast tumor before neoadjuvant therapy according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing; if negative for ER, assessment of progesterone receptor (PgR) must also be performed according to current ASCO/CAP guideline recommendations for hormone receptor testing
Patients must have had HER2 testing performed on the primary breast tumor before neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer; patients who have a primary tumor that is either HER2-positive or HER2-negative are eligible
At the time of definitive surgery, all removed axillary nodes must be histologically free from cancer; acceptable procedures for assessment of axillary nodal status at the time of surgery include:* Axillary node dissection* Sentinel node biopsy alone provided that at least 2 sentinel lymph nodes are removed; removal of at least 3 sentinel lymph nodes and use of dual tracer for lymphatic mapping are strongly recommended or* Sentinel node biopsy followed by axillary node dissectionNote: patients are eligible whether there is residual invasive carcinoma in the surgical breast specimen or whether there is evidence of pathologic complete response; patients who are found to be pathologically node-positive at the time of surgery, based on sentinel node biopsy alone, are candidates for A011202, a study developed by the Alliance in Oncology, an National Cancer Institute (NCI) Cooperative Group; if A011202 is open at the investigator's institution, patients should be approached about participating in the A011202 study
Patients with pathologic staging of ypN0(i+) or ypN0(mol+) are eligible
Patient who have undergone either a total mastectomy or a lumpectomy are eligible; (patients who have had a nipple-sparing mastectomy are eligible)
For patients who undergo lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS as determined by the local pathologist; additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection)
For patients who undergo mastectomy, the margins must be histologically free of residual (microscopic or gross) tumor
Documentation of axillary nodal positivity before neoadjuvant therapy by sentinel node biopsy alone
N2 or N3 disease detected clinically or by imaging
Patients with histologically positive axillary nodes post neoadjuvant therapy
Active collagen vascular disease, specifically dermatomyositis with a creatinine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma
Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
Histologic diagnosis of CD30-positive classical HL as defined by the 2008 World Health Organization (WHO) Classification of Hematological diseases; nodular lymphocyte predominant Hodgkin lymphoma is not eligible
Participants must have previously untreated HIV-classical HL (cHL), with the exception of up to 14 consecutive days of steroids, emergency radiation, or 1 prior cycle of cyclophosphamide to reduce tumor burden and improve hyperbilirubinemia in the setting of lymphoma related liver involvement
Karnofsky performance status > 30% (given the aggressiveness of this disease and the often severely debilitated nature of the patients at initial presentation)
Patients already receiving erythropoietin or granulocyte colony stimulating factor (GCSF) for treatment of HIV-related cytopenia are eligible
Participants are required to be on antiretroviral regimens that are in accordance with the current International Acquired Immune Deficiency Syndrome (AIDS) Society guidelines concurrently with chemotherapy; the specific agents are at the discretion of the investigator and the use of investigational agents currently available on an expanded access basis is allowed; use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) or ritonavir (includes Norvir or Kaletra), cobicistat, didanosine (Videx or Videx EC), or similar potent cytochrome P450 (CYP)3 inhibitors are prohibited; in order to be eligible, participants taking zidovudine or ritonavir, or cobicistat, didanosine, or other CYP3 inhibitors must change to a different regimen 7 days prior to therapy initiation; changes to HAART therapy during the study may be made if medically necessary (toxicity, failure of regimen, etc.); participants must be on HAART at least 7 days prior to therapy
Evidence of progressive multifocal leukoencephalopathy (PML) identified on the pretreatment magnetic resonance imaging (MRI)
Patients with history of John Cunningham (JC) virus identified in the cerebrospinal fluid (CSF) or previous history of PML will be excluded from the study
Cirrhosis secondary to any cause will be excluded
Surgical resection with curative intent within 8 weeks prior to registration
Patients must be deemed able to comply with the treatment plan and follow-up schedule
Significant pre-existing hearing loss, as defined by the patient or treating physician
NOTE: use of luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide or goserelin) is not allowed
Plan to treat with anastrozole for at least 12 months
Patients must not be currently taking (or have taken in the past 6 months) medication for active, chronic conditions, including rheumatoid arthritis, carpal tunnel syndrome, tenosynovitis, systemic lupus erythematosus, gout, fibromyalgia, or severe osteoarthritis involving the hands, wrists, hips, knees, feet or ankles; this includes analgesic medications or medications being taken with the purpose of treating pain or that may have an effect on pain (e.g. anti-depressants for help with pain or neuropathy, corticosteroid shots for arthritis); (Note: patients taking daily low dose aspirin are allowed to participate in this trial)
Patients must not have a prior history of deep vein thrombosis (DVT) or pulmonary embolism in the past 5 years
Patients must have worst pain rated as no worse than 3 out of 10 on the following question (i.e., a pain score of 0, 1, 2, or 3): �In the past week, how much pain have you had on a scale of 0 to 10, where 0 equals no pain and 10 means the worst pain you can imagine;  NOTE: this question regarding patient�s pain should be completed within one week prior to registration; this question may be asked orally prior to consent up to 7 days prior to registration; the response will be recorded on the registration checklist
Patients must have adequate hepatic, hematologic and renal functioning to be able to be administered anastrozole at the discretion of the treating physician
Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration; Note: patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink)
Pathologic stage III or IV HNSCC, including no distant metastases, based upon the following minimum diagnostic workup:* General history and physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration;* Examination by an ear nose throat (ENT) or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation* Pre-operative (op) Imaging of the head and neck: A neck computed tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via TRIAD; the report is to be uploaded into Rave* Chest CT scan (with or without contrast) or CT/PET that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
Absolute granulocyte count (AGC) >= 1,500 cells/mm^3
The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; Note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator�s discretion
Patients with feeding tubes are eligible for the study
Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
Prior allergic reaction to cetuximab
Patients undergoing allogeneic transplant must have, or be scheduled to have, an external tunneled central venous catheter (CVC) (Broviacs, Hickmans, tunneled percutaneously inserted central catheter [PICCs], etc.) and/or non-tunneled percutaneously inserted central catheter (PICC) that is expected to remain in place for an additional >= 3 months
Patients with acute myelogenous leukemia (AML) or relapsed acute lymphoblastic leukemia (ALL) that will receive chemotherapy with/without transplant must have, or be scheduled to have, an external tunneled CVC (Broviacs, Hickmans, tunneled PICCs, etc.) and/or non-tunneled PICC that is expected to remain in place for an additional >= 3 months
All other oncology patients that will receive chemotherapy with/without transplant must have, or be scheduled to have, an external tunneled CVC (Broviacs, Hickmans, tunneled PICCs, etc.) that is expected to remain in place for an additional >= 3 months
Patients with only totally implanted CVCs or ports are ineligible
Patients with a known allergy or hypersensitivity to CHG are ineligible
Patients with chronic, severe, generalized skin breakdown (such as generalized blistering, burns, severe graft versus host disease [GVHD] with open sores, etc.) are ineligible
Patients currently enrolled on Children's Oncology Group (COG) study ACCL0934 are not eligible until they have completed the infection observation period of that study
Patients scheduled to receive broad-spectrum prophylactic antibacterial therapy are ineligible; patients only receiving prophylaxis for Pneumocystis pneumonia (PCP) (trimethoprim [TMP]/sulfamethoxazole [SMX]) or encapsulated organisms (penicillin) are eligible
Patients receiving sorafenib at the time of enrollment and those who are scheduled to receive sorafenib as part of a treatment plan are ineligible
Patients using prophylactic antimicrobial locks in the CVC at the time of enrollment and those who are scheduled to receive antimicrobial locks in the CVC as part of a treatment plan are ineligible
Patients previously enrolled on this trial are ineligible
History of allergic reactions attributed to fluoropyrimidines (e.g., capecitabine, fluorouracil, fluorodeoxyuridine) or tetrahydrouridine
Unresectable stage IIIA or IIIB disease; patients must be surgically staged to confirm N2 or N3 disease; patients may have invasive mediastinal staging by mediastinoscopy, mediastinotomy, endobronchial ultrasound transbronchial aspiration (EBUS-TBNA), endoscopic ultrasound (EUS), or video-assisted thoracoscopic surgery (VATS)
Patients with any tumor (T) with node (N)2 or N3 are eligible; patients with T3, N1-N3 disease are eligible if deemed unresectable; patients with T4, any N are eligible
Patients with a pleural effusion, which is a transudate, cytologically negative and non-bloody, are eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field of radiotherapy
If a pleural effusion can be seen on the chest CT but not on chest x-ray and is too small to tap, the patient will be eligible; patients who develop a new pleural effusion after thoracotomy or other invasive thoracic procedure will be eligible
Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:* History/physical examination, including recording of pulse, blood pressure (BP), weight, and body surface area, within 45 days prior to registration* Whole body fludeoxyglucose-positron emission tomography (FDG-PET)/CT (orbits to mid-thighs) within 30 days prior to registration; PET/CT must be negative for distant metastasis* CT scan with contrast of the chest and upper abdomen to include liver and adrenals (unless medically contraindicated) within 30 days prior to registration* Magnetic resonance imaging (MRI) of the brain with contrast (or CT scan with contrast, if MRI medically contraindicated) within 30 days prior to registration
Atelectasis of the entire lung
Contralateral hilar node involvement
Exudative, bloody, or cytologically malignant effusions
Prior allergic reaction to the study drug(s) involved in this protocol
Must have baseline donor T cell chimerism of >= 20%
Patients who have had donor lymphocyte infusion (DLI) within 8 weeks prior to registration
Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
Participating participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications, when clinically indicated and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 8 weeks following study entry; as study-specific (antiretroviral-based) strata fill, however, only participants who are receiving the therapies eligible for the remaining open strata will be accrued
Participants must in the opinion of the investigator be capable of complying with this protocol
Prior treatment with cabozantinib (XL184)
The participant requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor xabans (Xa) inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
Patients should be capable of achieving imaging without the need for sedation or anesthesia
Serious intercurrent medical illness
Patients requiring emergency surgical intervention that would be inappropriately delayed by FLT-PET imaging
Patients must have magnetic resonance imaging (MRI) within 21 days of starting treatment
Must have recovered from the immediate post-operative period
INTRATUMORAL DRUG DISTRIBUTION STUDY PATIENTS:
Patients must be undergoing repeat surgery that is clinically indicated as determined by their care providers
Patients must have measurable contrast-enhancing progressive or recurrent glioblastoma by MRI within 21 days of starting treatment; patient must be able to tolerate MRIs
Patients may not be on anti-coagulants (warfarin, etc.) other than low-molecular weight heparin (LMWH)
All patients must have had an axillary ultrasound with fine needle aspiration (FNA) or core needle biopsy of axillary lymph nodes documenting axillary metastasis at the time of diagnosis, prior to or at most 14 days after starting neoadjuvant chemotherapy* Note: Biopsy of intramammary nodes does not fulfill eligibility criteria
Patients must have had estrogen receptor, progesterone receptor and HER2 status (by immunohistochemistry [IHC] and/or in situ hybridization [ISH]) evaluated on diagnostic core biopsy prior to start of neoadjuvant chemotherapy* Note: If HER2 status has not been clearly determined (i.e. equivocal/indeterminate), then patients should not be enrolled
No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis
A minimum of 1 sentinel node and a maximum of 6 total nodes (sentinel + non-sentinel) are identified and excised by the surgeon; patients who do not have an identifiable sentinel lymph node will not proceed to registration/randomization
At least one lymph node (sentinel or non-sentinel) with a metastasis greater than 0.2 mm in greatest dimension identified on intra-operative pathologic assessment* Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+)* Note: If on final pathology, more than 8 lymph nodes are seen pathologically, then the patient should discontinue study* Axillary lymph node dissection (ALND) is not to be performed prior to registration/randomization
For cases where ALND has not been performed and one of the following is true: 1) intra-operative evaluation of sentinel lymph node could not be/was not performed and final pathology identified a positive lymph node (sentinel or non-sentinel) with metastasis greater than 0.2 mm OR 2) lymph node (sentinel or non-sentinel) considered negative on intra-operative evaluation was found to be positive on final pathology (with metastasis greater than 0.2 mm)
At least one lymph node (sentinel or non-sentinel) with a metastasis greater than 0.2 mm in greatest dimension identified on final pathology (for cases where intra-operative evaluation was not performed, or was negative and completion dissection was not performed)
Among the minimum of 1 and the maximum of 6 lymph nodes (sentinel + non-sentinel) identified and excised by the surgeon, no more than 8 lymph nodes (sentinel and non-sentinel) were found by the pathologists to have been actually excised; * Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+)
Patients enrolling in the expansion cohorts must have disease amenable to biopsy and be willing to undergo pre-and post-treatment biopsies
Phase II only: patients with colorectal cancer with known microsatellite instability (MSI)-high disease who have previously been treated with immunotherapy or who have refused treatment with immunotherapy
HEALTHY VOLUNTEER BLOOD DONORS
No history of bleeding problems; not taking aspirin or any medication that may affect erythrocyte biochemistry
Lipase < 2.0 x ULN; no radiologic/clinical evidence of pancreatitis
Prior treatment with cabozantinib
Therapeutic anticoagulation with warfarin, antiplatelet agents (e.g., clopidogrel), thrombin, or Factor Xa inhibitors is not allowed; therapeutic anticoagulation with low molecular weight heparin (LMWH) is allowed as well as prophylactic anticoagulation using low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and LMWH
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)
Patients must have successfully completed therapy with sipuleucel-T within 3-7 days of planned CYT107 study drug treatment
Prior orchiectomy or must be on ongoing luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g., degarelix) therapy
Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease prostate specific antigen (PSA) levels (e.g. saw palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for at least 30 days prior to study treatment
Testosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy)
Prior �systemic� radiopharmaceuticals (strontium, samarium, radium 223 dichloride) must be completed >= 8 weeks prior to enrollment
Prostate cancer pain requiring regularly scheduled narcotics
Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness
Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of CYT107 hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
Patients who have a history of any hematopoietic malignancy
History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume [FEV] > 60% of predicted for height and age required in patients with prolonged smoking history or symptoms of respiratory dysfunction)
History of allergic reactions attributed to fluoropyrimidine (e.g., capecitabine, fluorouracil, fluorodeoxyuridine) or tetrahydrouridine
Malabsorption syndrome or other conditions that would interfere with intestinal absorption
History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, including but not limited to established allergic reaction to benzodiazepines, or romidepsin; agents that alter gastric pH may change MLN8237 absorption are not permitted; proton pump inhibitors need to be stopped 4 days prior to the first dose of MLN8237; histamine-2 (H2) receptor antagonists are not permitted from the day prior (day -1) through to the end of MLN8237 dosing; antacid preparations are not permitted for 2 hours before or 2 hours after administration of MLN8237
Co-administration of enzyme-inducing antiepileptic drugs, rifampin, rifabutin, rifapentine, or St. John�s wort is not permitted; concurrent bisphosphonate therapy is allowed if it was started before study entry and is maintained at recommended dosing intervals; bisphosphonate therapy may not be initiated after study entry
Any serious active disease or co-morbid condition, which in the opinion of the principal investigator, will interfere with the safety or compliance of the trial
Ejection fraction (EF) < 40% or myocardial infarction (MI) within the past 3 months; known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
Patients must have pathologically confirmed relapsed or refractory classical Hodgkin lymphoma (cHL); a biopsy at any relapse is acceptable; other histologies including lymphocyte predominant (LP) HL are not permitted
Patients must have forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
Patients must not have previously existing hypersensitivity to brentuximab vedotin or ipilimumab
Patients must not have a serious medical or psychiatric illness likely to interfere with study participation
Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
Routine vaccinations, including seasonal influenza, should be given at least 2 weeks prior to study treatment; vaccines are not prohibited on study, but must be given at least 6 weeks after cycle 1 and not within 7 days of treatment
Patients registering to Arms D, E, F, G, H, I, X, Y must not currently be smoking tobacco or other substances and must not have smoked within the past 6 months
RANDOMIZED PHASE II (ARMS K AND L): Patients must have FEV1/FVC > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and FVC all > 50% predicted value; all pulmonary function tests must be obtained within one month prior to registration
Patients must be willing to submit blood for pharmacokinetics; sites must order S1221 pharmacokinetic (PK) kit immediately after registration; the Southwest Oncology Group (SWOG) patient identification (ID) number must be provided on the S1221 PK Kit request form
Patients with melanoma must have a serum lactate dehydrogenase (LDH) test performed within 28 days prior to registration
Postmenopausal, verified by: * Post bilateral surgical oophorectomy, or* No spontaneous menses >= 1 year or* No menses for < 1 year with follicle-stimulating hormone (FSH) and estradiol levels in postmenopausal range, according to institutional standards
Invasive breast cancer is estrogen receptor (ER) positive with an Allred score of 6, 7 or 8 by local institution standard protocol; if an Allred score is not reported on the diagnostic pathology report, ER positivity in > 66% cells is eligible; if ER positivity is =< 66%, the staining intensity (weak, intermediate, strong) is needed to calculate the Allred score to determine eligibility
Invasive breast cancer is human epidermal growth factor receptor 2 (HER2) negative; a patient is considered to have HER2 negative breast cancer if one of the following if one of the following applies: * 0 or 1+ by immunohistochemistry (IHC) and in situ hybridization (ISH) not done* 0 or 1+ by IHC or ISH ratio (HER2 gene copy/chromosome 17) < 2* 2+ by IHC and ISH ratio (HER2 gene copy/chromosome 17) < 2
Premenopausal status
Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d�orange without erythema)
Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration
Tumor ER Allred score between 0-5 or HER2 positive by IHC (3+) or amplified by FISH > 2.0
Surgical axillary staging procedure prior to study entry; Note: fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted
Breast implants are contraindicated only if the implant precludes the required research biopsies or interferes with palpating the breast lesion
Prior thoracic radiation allowed only if there is minimal to no overlap with the treatment area estimated at the time of consultation, and there is no cumulative esophageal dose that exceeds more than 50% of the maximal acceptable dose tolerance
Patients must have a diagnosis of relapsed or refractory CD22-positive acute leukemia including B-ALL, mixed phenotype leukemia (biphenotypic), or Burkitt�s leukemia based on World Health Organization (WHO) classification; patients with bilineal leukemia are excluded
Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine
For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria:* Patient is in second salvage or more and B1931022 has been considered and ruled out as a treatment option; OR* Patient was treated on the standard of care arm of B1931022 and failed therapy
Patients must not have any other serious concurrent disease or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would put the patient at undue risk of undergoing therapy
Patients must have a peripheral blast count < 25,000/uL within 2 days prior to registration; (treatment with hydroxyurea and steroids is permitted to bring the countdown)
Patients must not have evidence or history of veno-occlusive disease or sinusoidal obstruction syndrome
Patients must not have a history of chronic liver disease (or cirrhosis)
Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration
Prior malignancy other than acute leukemia is allowed, provided it is in remission and there is no plan to treat the malignancy at the time of registration
Patients planning to enroll in this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation
Patients must have metastatic alveolar soft part sarcoma that is not curable by surgery; patients who have surgically resectable tumors with metastasis will be considered on a case-by-case basis
Any degree of prior treatment is allowed, including other anti-angiogenic treatments (e.g., vascular endothelial growth factor receptor 2 [VEGFR2] inhibitors or bevacizumab); patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery
Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity of pharmacokinetics (PK) of AZD2171 will be determined following review of their case by the principal investigator; efforts should be made to switch patients with brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications one week prior to starting therapy
Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, ibuprofen, pentamidine)
Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
Patients with abnormal liver function will be eligible and will be grouped according to the criteria described; patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes
Patients with biliary obstruction for which a stent has been placed are eligible, provided the stent has been in place for at least 10 days prior to the first dose of belinostat and the liver function has stabilized; two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function; there should be no evidence of biliary sepsis
Patients should not have taken valproic acid, another histone deacetylase (HDAC) inhibitor, for at least 2 weeks prior to enrollment
Having chronic hepatitis B or C will not exclude patients from participating if they are otherwise eligible; however, requiring treatment with interferon is an exclusion; patients must be stable without having received interferon in at least 4 weeks
Patients with the following types of histologically documented solid tumors:* Estrogen receptor (ER) positive (+)/progesterone receptor (PR)+, ER+/PR negative (-), or ER-/PR+ breast cancer* Gynecologic tumors (endometrial, ovarian, uterine, fallopian tube, peritoneal, etc.)* Desmoid tumors* Tumors that are ER+ or PR+ by immunohistochemistry (including low-level expression) such as non-small cell lung, colorectal, and prostate
Patients enrolled based on tumor ER/PR status must have ER/PR status confirmed by the Laboratory of Pathology, National Institutes of Health (NIH); ER/PR status will be determined on a metastatic site, if possible; otherwise, the original site or available tissue will be acceptable
Every effort should be made to switch patients taking drugs that are known to be sensitive substrates of these enzymes to other medications 1 week prior to starting therapy; if a patient�s medication cannot be switched, the patient�s eligibility will be determined following a review of their case by the principal investigator
Patients with untreated spinal cord metastases or metastases close to vital organs (as determined by the principal investigator) are excluded
Patients with a history of deep vein thrombosis must be on anti-coagulation therapy prior to enrollment; patients requiring prophylactic anti-coagulation are eligible
Patients with NF1 and inoperable PN defined as PN that cannot be surgically completely removed without risk for substantial morbidity due to encasement of, or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN has to cause (stratum 1) or have the potential to cause (stratum 2) significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions; patients will be enrolled into stratum 1 or 2 based on PN related morbidity; histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings, but should be considered if malignant degeneration of a PN is clinically suspected; a PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches; a spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve; in addition to PN, all study subjects must have either positive genetic testing for NF1 or have at least one other diagnostic criterion for NF1 listed below (National Institutes of Health [NIH] Consensus conference):* Six or more caf�-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)* Freckling in axilla or groin* Optic glioma* Two or more Lisch nodules* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)* A first-degree relative with NF1
Patients must have at least one measurable PN, defined as a lesion of at least 3 cm measured in one dimension; patients who underwent surgery for resection of a PN are eligible provided the PN was incompletely resected and is measurable
PHASE II: Measurability and suitability for volumetric MRI analysis of the target PN must be confirmed with the NCI Pediatric Oncology Branch (POB) prior to enrolling a patient; the target PN will be defined as the clinically most relevant PN, which has to be amenable to volumetric MRI analysis; PN will be classified as �typical PN� versus �nodular PN� versus �solitary nodular PN prior to enrollment
Patients > 16 years of age must have a Karnofsky performance level of >= 70%, and children =< 16 years old must have a Lansky performance of >= 70%; patients who are wheelchair bound because of paralysis secondary to a plexiform neurofibroma should be considered ambulatory when they are up in their wheelchair; similarly, patients with limited mobility secondary to need for mechanical support (such as an airway PN requiring tracheostomy or continuous positive airway pressure [CPAP]) will also be considered ambulatory for the purpose of the study
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism
PHASE I: Patients who anticipate the need for surgical intervention within the first three cycles (3 months), as surgical intervention during the period of dose limiting toxicity (DLT) evaluation may affect analysis of adherence and/or make the subject inevaluable
Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol; prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target PN on MRI
Supplementation with vitamin E greater than 100% of the daily recommended dose; any multivitamin containing vitamin E must be stopped prior to initiation of therapy
Ophthalmologic conditions:* Current or past history of central serous retinopathy* Current or past history of retinal vein occlusion* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma may be eligible after discussion with the study chair* Subjects with any other significant abnormality on ophthalmic examination should be discussed with the study chair for potential eligibility* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Clinical judgement by the investigator that the patient should not participate in the study
Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
Warfarin and its derivatives are not allowed; patient can be receiving low molecular weight heparin if clinically indicated
Diffusing capacity of the lung for carbon monoxide (DLCO)/alveolar volume (VA) and forced expiratory volume in 1 second (FEV-1.0) >= 60% of predicted on pulmonary function tests
Patients with more than 30% replacement of hepatic parenchyma by tumor or any history of drug related hepatic encephalopathy
History of complex ventricular or supraventricular arrhythmias
History of severe asthma or presently on chronic inhaled corticosteroid medications (patients with a history of mild asthma controlled with inhaled bronchodilators are eligible)
Patients with prostate cancer can continue to receive treatment with gonadotropin releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on therapy
Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of AZD1775 will be determined following review by the principal investigator
TUMOR BIOPSY SEQUENCING: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents areare eligible to participate and may continue this treatment; patients with prostate cancer may continue luteinizing hormone-releasing hormone (LHRH) agonists or antagonists
TUMOR BIOPSY SEQUENCING: Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with Crohn�s disease or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow tablets or capsules whole; tablets or capsules must not be crushed or chewed; nasogastric or gastrostomy tube (G-tube) administration is not allowed
TUMOR BIOPSY SEQUENCING: Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded; low molecular weight heparin is permitted for prophylactic or therapeutic use
TREATMENT: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment; patients with prostate cancer may continue LHRH agonists or antagonists
TREATMENT: Patients who have received prior everolimus or other mechanistic target of rapamycin (mTOR) inhibitors or those with known intolerance or hypersensitivity to other rapamycin analogs (e.g., sirolimus, temsirolimus) would not be eligible to receive everolimus on study; if these patients have mutations of interest in pathways other than the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (pI3K) pathway, they will be eligible to receive agents based on that mutation
TREATMENT: Patients with known hypersensitivity reaction to dacarbazine are ineligible to receive temozolomide
TREATMENT: Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with Crohn's disease or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow tablets or capsules whole; tablets or capsules must not be crushed or chewed; nasogastric or G-tube administration is not allowed
TREATMENT: Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded; low molecular weight heparin is permitted for prophylactic or therapeutic use
Patients with newly diagnosed DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible without histologic confirmation* Patients with brainstem tumors that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma, gliosarcoma, diffuse midline glioma with histone H3 K27M mutation, or anaplastic mixed glioma; patients with pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible* Patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician* Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date
Any known hypersensitivity or contraindication to the components of the study drug AZD1775
Patients must not receive metformin for at least 5 days prior to enrollment and for the duration of study treatment
Major surgical procedures =< 28 days of beginning study treatment, or minor surgical procedures (including ventriculoperitoneal [VP] shunt placement or stereotactic biopsy of the tumor) =< 7 days; no waiting period required following port-a-cath or other central venous access placement
Subjects must have completed at least 3 half-life periods from the last dose of monoclonal antibody prior to registration * Note: a list of half-lives of commonly used monoclonal antibodies is available on the Pediatric Brain Tumor Consortium (PBTC) website under Generic Forms and Templates
Stratum 2: patients must have received radiation therapy, which may include gamma knife or phosphorus-32 (P32)* More than 6 months from the time of enrollment if the recurrence is predominantly solid* More than 12 months from the time of enrollment if the recurrence is predominantly cystic
At least 7 days since the completion of therapy with a hematopoietic growth agent (filgrastim, sargramostim, and erythropoietin) and 14 days for long-acting formulations
Minimum weight 20 kilograms is required to be eligible for the study since the minimum injection volume of SYLATRON is 0.05 ml, 20 mcg, subcutaneously (SQ) as suggested by Merck
Patients must have evidence of radiographic progression as defined below:* Stratum 1: defined as >= 25% increase in the product of the greatest perpendicular diameters of the tumor as a whole (solid and cystic component) AND >= 0.4 cm increase in each of at least two dimensions of the tumor as a whole OR any new or worsening neurologic/vision deficit in conjunction with a lesser change in the solid or cystic component* Stratum 2: ** For patients more than 6 months following radiation therapy (RT) (including radiosurgery or P32), progression is defined as a >= 25% increase in the product of the greatest perpendicular diameters of the solid component AND >= 0.4 cm increase in each of at least two dimensions of the solid component** For patients more than 12 months following RT (including radiosurgery or P32), progression is defined as >= 25% increase in each of the product of the greatest perpendicular diameters of the solid tumor AND >= 0.4 cm increase in each of at least two dimensions of the solid tumor; patients demonstrating predominantly cystic progression more than 12 months after RT must show a continued increase in the cystic component on two serial MRI scans performed at least 4 weeks apart OR re-accumulation of the cyst following one or more cyst aspirations; patients with progressive neurologic signs and/or symptoms associated with isolated cyst formation or progression are eligible if the neurologic signs and/or symptoms do not improve within 4 weeks of cyst aspiration
Stratum 1 patients: must not have had > 3 surgical debulking procedures/resections
Patients must not have a severe psychiatric illness, including major depression or any previous suicide attempts
Patients must not be on phenytoin, warfarin or methadone
Patients must not have known hypersensitivity reactions, such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Steven-Johnson syndrome, and toxic epidermal necrolysis to interferon alpha or any other products component
Subjects with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
Progression on lenalidomide as part of first line therapy (lenalidomide-refractory disease)* Lenalidomide-refractory disease is defined as disease progression on or progression within 60 days of the last dose of a lenalidomide-based treatment; patients should have received at least 2 cycles of a lenalidomide-based regimen to be evaluable for refractoriness; examples: 1) progression on lenalidomide maintenance therapy after initial induction +/- consolidation; 2) initial response followed by progression on continuous lenalidomide-dexamethasone +/- elotuzumab or daratumumab
Pomalidomide naive disease
No G-CSF (filgrastim) or GM-CSF (sargramostim) within 7 days of registration or pegfilgrastim within 14 days of registration to meet eligibility criteria
Therapeutic level dosing of warfarin can be used with close monitoring of PT/INR by the site; exposure may be decreased due to enzyme induction when on treatment, thus warfarin dosing may need to be adjusted based upon PT/INR; consequently, when discontinuing dabrafenib, warfarin exposure may be increased and thus close monitoring via PT/INR and warfarin dose adjustments must be made as clinically appropriate; prophylactic low dose warfarin may be given to maintain central catheter patency
Patients with history of rat sarcoma (RAS) mutation-positive tumors are not eligible regardless of interval from the current study; Note: prospective RAS testing is not required; however, if the results of previous RAS testing are known, they must be used in assessing eligibility
Any condition which in the investigator�s opinion makes the subject unsuitable for study participation
The tumor is considered to be radioactive-iodine refractory by any of the following criteria:* Total lifetime dose of radioactive iodine > 600 mCi* Absent or insufficient radioactive iodine uptake in either all lesions or an index lesion which has never been resected or received external beam radiation therapy as documented on a radioactive iodine scan (insufficient uptake must be confirmed by either an endocrinologist or nuclear medicine physician)* Progression of disease (by imaging or thyroglobulin) within 6 months of radioactive iodine treatment* Fludeoxyglucose F 18 (FDG)-avid lesion (standard uptake variable maximum [SUVmax] >= 3) on a FDG-positron emission tomography (PET) scan
Patient must agree to allow 3 separate biopsies of any malignant lesion; biopsies do not need to be done if:* Tumor is not considered accessible by either the investigator or the person performing the biopsy (it is determined the risk is too high due to location near vital organs or too great of a risk of an adverse event)* Patient is on anticoagulation and it would be unsafe to temporarily hold the anticoagulation* Consent of the principal investigator (PI) not to have a biopsy done* A minimum of 8 subjects must participate in the biopsy part of the study
Patients with a history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; Note: prospective RAS testing is not required; however if the results of previous RAS testing are known, they must be used in assessing eligibility
Scheduled to receive chemotherapy with an anthracycline (doxorubicin [doxorubicin hydrochloride] or epirubicin [epirubicin hydrochloride])
Able to hold breathe for 10 seconds
Patients with breast implants are usually permitted to have an magnetic resonance imaging (MRI); check with the MRI technician to confirm
It is recommended the lipid profile be drawn fasting >= 8 hrs; serum lipid profile: total cholesterol/high-density lipoprotein (HDL)/low-density lipoprotein (LDL)/triglycerides (LDL levels prior to chemotherapy must be =< 190 mg/dl), within 30 days prior to enrollment* If labs are drawn non-fasting and LDL levels are >= 190 mg/dl the lipid profile should be repeated fasting to determine eligibility
Thyroid stimulating hormone (TSH) =< 1.5 times ULN, within 30 days prior to enrollment
40 to 75 years of age with diabetes per American College of Cardiology (ACC)/American Heart Association (AHA) ACC/AHA 2013 guidelines
Significant ventricular arrhythmias (> 20 premature ventricular contractions [PVCs]/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response
Current or history of hepatic dysfunction
Uncontrolled hypothyroidism
Recent extended history of constant-recurrent substance abuse or another medical condition that might compromise safety or the successful completion of the study
Patients with ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices
Current use of the following cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 3A4) inhibitors are not allowed: boceprevir, clarithromycin, cyclosporine (oral), darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, gemfibrozil, grapefruit juice > 1 liter per day, itraconazole, lopinavir plus ritonavir, nelfinavir, saquinavir plus ritonavir, telaprevir, tipranavir plus ritonavir
Current use of rifampin and digoxin
Symptomatic claustrophobia
Clinical American Joint Committee on Cancer (AJCC) (AJCC, 7th ed.) II, IIIA or IIIB (with non-operable disease; non-operable disease will be determined by a multi-disciplinary treatment team within 60 days prior to registration; note: for patients who are clearly nonresectable, the case can be determined by the treating radiation oncologist and/or a medical oncologist or pulmonologist * Patients who present with N2 or N3 disease and an undetectable NSCLC primary tumor are eligible* Patients who refuse surgery are eligible* Patients who develop local recurrence after surgery and rendered candidate for definitive concurrent chemoradiation are also eligible* Patients who have received systemic treatment (up to 4 cycles of induction chemotherapy, or up to 6 months of targeted therapy) are eligible
Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:* History/physical examination within 30 days prior to registration including resting heart rate;* Fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) scan for staging within 60 days prior to registration* Magnetic resonance imaging (MRI) scan with contrast of the brain (preferred) or CT scan of the brain with contrast within 60 days prior to registration; * Forced expiratory volume in one second (FEV1) >= 0.8 liter or >= 35% predicted with or without bronchodilator within 90 days prior to registration;** Patients who meet the criterion above without oxygen (O2), but who need acute (started within 10 days prior to registration) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable
Patients with non-malignant pleural effusion are eligible* If a pleural effusion is present, the following criteria must be met to exclude malignant involvement:** When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative** Exudative pleural effusions are excluded, regardless of cytology** Effusions that are minimal (i.e, not visible on chest x-ray) that are too small to safely tap are eligible
Unintentional weight loss > 10% within 30 days prior to registration
INCLUSION CRITERIA FOR PHYSICIANS
Oncology physicians must work at a National Cancer Institute (NCI) Community Oncology Research Program (NCORP) practice site with no plans to leave that NCORP practice site or retire at the time of enrollment into the study
INCLUSION CRITERIA FOR PATIENTS
Plan to be on chemotherapy or other allowable treatment for at least 3 months (minimum 70 days) and be willing to come in for study visits* The plan for treatment should be for at least 3 months at time of study enrollment; the treatment can stop earlier during the study at the discretion of the physician and patient (e.g., due to progression as noted through imaging, toxicity, or patient preference)
Have at least one geriatric assessment domain meet the cut-off score for impairment other than polypharmacy
Participant has adequate understanding of the English language
EXCLUSION CRITERIA FOR PATIENTS
For cohort 3 only, patients must be able to safely undergo pre and post-treatment biopsy, i.e., at least one readily accessible lesion or palpable lymph node metastasis arising from any solid tumor cancer or lymphoma* NOTE: this may include cutaneous and subcutaneous tumors using injection by palpation or ultrasound guidance* NOTE: the target lesion must be >= 1.5 cm on its longest diameter, be at least 5 mm thick, and have distinct borders* NOTE: deep seated lesion(s) that are deemed hazardous to inject or lesion(s) close to vital structures that might be impinged with tumor swelling are excluded as targeted tumor* NOTE: cohort 3 should be selected for patients with injectable cutaneous lesion(s), unless the patient elects not to receive IT injection and/or undergo pre and post-treatment biopsies
Both men and women of all races and ethnic groups are eligible for this trial
Hemoglobin >= 10 g/dL (may be transfused but must be stable without clinical evidence of ongoing blood loss or hemolysis)
No history of severe chronic obstructive pulmonary disease (COPD) or emphysema or interstitial lung disease currently on home supplemental oxygen; patients with NSCLC with stable COPD or emphysema not requiring supplemental oxygen are eligible
Patients with thyroid disease should be excluded unless euthyroid on suppressive or replacement therapy
Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
The following concomitant medications are not allowed during navitoclax administration: clopidogrel, ibuprofen, tirofiban, warfarin, and other anticoagulants, drugs, or herbal supplements that affect platelet function are excluded, with the exception of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor
Newly diagnosed patients with histologically proven ALCL (International Classification of Diseases for Oncology [ICD-0] code: 9714/3)
Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local institutional standards)
If the lab abnormality is thought to be due to the lymphoma the patient is eligible and dose adjustments should be made
Patients with disease limited to the skin are not eligible, regardless of how wide-spread
Patients with an immunodeficiency that existed prior to diagnosis such as primary immunodeficiency syndromes or organ transplant recipients are not eligible
Patients who weigh < 10 kg are not eligible
Negativity for the Philadelphia chromosome must be established by conventional cytogenetics, fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR); patients who are negative for the Philadelphia chromosome by conventional cytogenetics must have FISH or PCR performed for BCR/ABL to exclude occult translocations
Patient must not have a concurrent active malignancy for which they are receiving treatment
Serum creatinine < 2 mg/dl; NOTE: the above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration
Patient should be human leukocyte antigen (HLA) typed (A, B, C, DR and DQ) during induction therapy phase or a written explanation for not undergoing HLA typing on the flow sheet
Patient must not have intercurrent organ damage or medical problems that will jeopardize the outcome of therapy (i.e., psychiatric disorder, drug abuse, pregnancy)
Patient must not have an antecedent hematologic disorder
Patients must have achieved a CR or CRi
Patients who have achieved a CR or CRi must have maintained peripheral blood evidence of a CR or CRi
RANDOMIZATION TO BLINATUMOMAB OR NO BLINATUMOMAB-STEP 3
A suitable donor must be identified; there are no restrictions on donor type and can include a matched sibling, a matched or mismatched unrelated donor, a family haplotype matched donor or a cord blood donor (single or double)
Patients must be considered reliable enough to comply with the medication regimen and follow-up, and have social support necessary to allow this compliance
CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging BM aspirate and biopsy
Patients who have adenocarcinomas of the ampulla, distal bile duct, and duodenum
Patients who have had surgery within 4 weeks of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc), celiac plexus block, and biliary stent placement
Patients with radiographic ascites that is apparent on physical exam or requiring medical intervention (medication or procedures) in the 2 months prior to enrollment
Patients with a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide (DMSO), fetal bovine serum, or trypsin (porcine origin)
Women with a positive pregnancy test on enrollment or prior to investigational product administration
Sexually active fertile men not using effective birth control if their partners are WOCBP
Patients must NOT be taking metformin or have been on metformin in the past 6 months
HSIL comprising 2 or more lesions, or anal HSIL in at least 2 octants, or anal HSIL that has recurred or is persistent after prior ablative treatmentNote: HSIL should be in the anal canal at either the squamocolumnar junction or distal anus on HRA at screening or randomization; the extent of HSIL should be based on available biopsy results and visual appearance
Anal HSIL lesions are visible at randomization and no lesions are suspicious for invasive cancer
Participants must, in the opinion of the Investigator, be capable of complying with the requirements of this protocol including self-administration of study treatment
For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current �Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents� and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to randomization for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to randomization
History of anal cancer
Prior intra-anal use of topical 5-fluorouracil 5% or imiquimod 2.5%, 3.75% or 5% for treatment of HSIL at any point, use of intra-anal or topical 5-fluorouracil 5% or imiquimod 2.5%, 3.75% or 5% for treatment of condyloma within 6 months prior to randomization or perianal imiquimod 2.5%, 3.75% or 5% or topical 5-fluorouracil 5% within 6 months prior to randomization
Extensive concurrent perianal or lower vulvar HSIL or condyloma requiring a different treatment modality than the study treatment, or treatment that cannot be deferred in observation arm, per examining provider
Condyloma occupying more than 50% of the circumference of the anal canal or that obscures a satisfactory exam
Ongoing use of anticoagulant therapy other than aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) that places the participant at increased bleeding risk in the opinion of the site investigator
Treatment for anal or perianal HSIL, low-grade squamous intraepithelial lesion (LSIL) or condyloma within 4 months of randomization; please note that infrared coagulation (IRC) or electrocautery of a biopsy site to stop bleeding does not constitute treatment
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or similar drugs in the past
Any other medical condition that in opinion of investigator would place patient at increased risk for toxicity during pomalidomide treatment (i.e. history of recurrent or serious thromboembolic events)
Patients have failed at least one previous induction course of intravesical BCG, defined as histologically confirmed persistent or relapsing tumor present on post-BCG endoscopic evaluation; all BCG failures will be considered for inclusion into the study, including BCG-refractory, -resistant, and -relapsing; for the purposes of the study, �BCG-refractory� and �BCG-resistant� subjects will be considered to have �BCG-persistent� disease
Computerized tomography (CT) urogram or magnetic resonance imaging (MRI) urogram; if urogram protocol not available or contrast allergy/poor renal function preclude such imaging, then noncontrast CT or MRI of the abdomen/pelvis within 45 days of study entry will suffice
History of allergy or untoward reaction to prior vaccination with vaccinia virus
Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
Medical conditions which, in the opinion of the investigators, would jeopardize the patient or the integrity of the data obtained
Serious hypersensitivity reaction to egg products
Patients unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczematoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV)
Proteinuria =< +1 on dipstick or =< 1 gram/24 hours
Patients with active hemolysis should be excluded
No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes
Any condition or medical problem in addition to the underlying malignancy and organ dysfunction which the investigator feels would pose unacceptable risk
Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
Part A: Patients with relapsed or refractory solid tumors, including patients with primary or metastatic CNS tumors
Part B: Patients with relapsed or refractory neuroblastoma
Part C: Patients with relapsed or refractory medulloblastoma or CNS PNET
Part D: Patients with relapsed or refractory rhabdomyosarcoma
At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
Patients previously treated with irinotecan are eligible for this study
Patients with a history of allergic reaction to irinotecan, cephalosporins or a severe penicillin allergy are not eligible
Potassium > 3 and < 5.5 mEq/L
Magnesium > 1.2 and < 2.5 mEq
Therapeutic level dosing of warfarin can be used with close monitoring of PT/INR by the site; exposure may be decreased due to enzyme induction when on treatment, thus warfarin dosing may need to be adjusted based upon PT/INR; consequently, when discontinuing dabrafenib, warfarin exposure may be increased and thus close monitoring via PT/INR and warfarin dose adjustments must be made as clinically appropriate; prophylactic low dose warfarin may be given to maintain central catheter patency
Patients with history of activating RAS mutation positive tumors regardless of interval from current study; however, patients may have concurrent BRAFV600 and RAS mutations in the tumor to be treated with protocol therapy
Histologic documentation: newly diagnosed World Health Organization (WHO) grade IV intracranial glioblastoma or gliosarcoma; GBM with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q codeleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status
Patients who have had a local MGMT testing that is unmethylated are not allowed to participate
Tumor MGMT promoter hypermethylation determined by central testing at MD Anderson
Progression: patients deemed to have progressive disease based on clinical deterioration after chemoradiation or radiographic progression outside of the radiation field are not eligible; patients deemed to have pseudoprogression are eligible
Concomitant medications: patients receiving anticoagulation should be on stable dose 2 weeks prior to registration
Patients must be platinum-resistant (platinum-free interval < 6 months) or have platinum-refractory disease as per Gynecologic Cancer Intergroup Committee (GCIC) criteria; disease progression has to be radiologic or clinical; biomarker progression with CA125 after a platinum based regimen would not be sufficient evidence of disease progression; the patients must have had radiological progression to that regimen
Hemoglobin >= 90 g/L* Blood transfusions are allowed at any time during the screening, treatment or follow-up period, according to the center recommendations
Radioactive iodine (RAI)-refractory disease defined as 1 or more of the following:* Patients who have received greater than 600 mCi of radioactive iodine in their lifetime OR* RAI-avid metastatic lesion which remained stable in size or progressed despite RAI treatment within 9 months of RAI treatment OR* 10% or more increase in serum thyroglobulin (on thyroid-stimulating hormone [TSH]-suppression) within 9 months of RAI treatment OR* Index metastatic lesion non-RAI avid on a diagnostic RAI scan OR* Presence of fluorodeoxyglucose (FDG) avid metastatic lesions on positron emission tomography (PET)/CT scan (standardized uptake values [SUV]max > 5 of any single lesion)
SCREENING/PRE-SCREENING REGISTRATION:
Patients must also be offered participation in banking for future use of specimens
Patients must be willing to provide prior smoking history as required on the S1400 Onstudy Form
United States (U.S.) patients who can complete the survey and the interview by telephone or email in English must be offered participation in the S1400GEN survey ancillary study; NOTE: Patients enrolled to S1400 prior to revision #12 are not eligible for the S1400GEN survey ancillary study; study physicians will provide participants with a hard copy of the survey (at the time of informed consent) to improve tracking and comprehension during the interview
SUB-STUDY REGISTRATION:
Patients whose biomarker profiling results indicate the presence of an EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion are not eligible
Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
Patients must have documented low-grade serous carcinoma; confirmation must occur by prospective pathology review prior to study entry; the prospective pathology review can be done on tissue from the recurrent carcinoma or from original diagnostic specimen
If letrozole is selected as the control therapy, patients must be postmenopausal, either following bilateral oophorectomy or at least 5 years after spontaneous menopause; patients within 5 years of spontaneous menopause or who have had a hysterectomy without bilateral oophorectomy must have postmenopausal luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels; patients on hormone replacement therapy (HRT) must agree to withdrawal of hormone therapy before letrozole is started
Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject�s safety, obtaining informed consent or compliance to the study procedures
Patient has not had prior treatment with blinatumomab
Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos)
Patients with pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved)
Biopsy proven (from primary lesion and/or lymph nodes) diagnosis of cancer of the nasopharynx
Sites are required to complete Step 1 registration before submitting specimens for EBV DNA analysis* Patients must have detectable pretreatment plasma EBV DNA, determined by the central lab prior to Step 2 registration* For patients who have detectable plasma EBV DNA tested at one of the credentialed central labs within 28 days prior to Step 1 registration: that test result can be used for eligibility without the need for re-testing; to use this test result for eligibility, the central lab must enter the test result through the pathology portal
Stage II-IVB disease (American Joint Committee on Cancer [AJCC], 7th edition [ed.]) with no evidence of distant metastasis, based upon the following minimum diagnostic workup:* History/physical examination by a Medical Oncologist or Clinical Oncologist or Radiation Oncologist or Ear, Nose, Throat specialist (ENT), which must include an endoscopic evaluation, a complete list of current medications, and assessment of weight and weight loss in the past 6 months within 21 days prior to registration* Evaluation of tumor extent with one of the following combinations required within 28 days prior to registration:** Magnetic resonance imaging (MRI) of the nasopharynx and neck; or computed tomography (CT) of the nasopharynx and neck with =< 3 mm contiguous slices with contrast and bone windows (to evaluate base of skull involvement). ** MRI of the nasopharynx and positron emission tomography (PET)/CT (with contrast) of the neck*** Note: If a treatment planning CT scan is used, it must be with =< 3 mm contiguous slices with contrast and be read by a radiologist* To rule out distant metastasis, patients must undergo the following imaging within 28 days prior to registration:** A CT scan with contrast of the chest and abdomen (required), and the pelvis (optional), or a total body PET/CT scan (non-contrast PET/CT is acceptable)** A bone scan only when there is suspicion of bone metastases (a PET/CT scan can substitute for the bone scan)
Patients with hearing loss assessed to be primarily sensorineural in nature, requiring a hearing aid, or intervention (i.e. interfering in a clinically significant way with activities of daily living); a conductive hearing loss from tumor-related otitis media is allowed
Prior allergic reaction to the study drug(s) involved in this protocol
Patients with undetectable pre-treatment plasma EBV DNA
At least one focus of HSIL must be identified that is not within a condyloma that may be treated after enrollment into the study
For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current �Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents� and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to enrollment for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment
Men randomized to the treatment arm should not father a baby while receiving topical treatment during this study; men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment during the study, and for 2 weeks after stopping topical treatment
Participant is willing to be randomized and able to comply with the protocol
Clinician is comfortable that cancer has adequately been ruled out and is willing to follow the participant for up to 5 years without treatment of the HSIL
Treatment or removal of HSIL less than 6 months prior to randomization
Participant has symptoms related to HSIL and would benefit more from immediate treatment than from entry into the study and potential for randomization to active monitoring arm
Participants who only have a single HSIL lesion that is likely to be removed entirely with the initial screening biopsy
Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
Participant plans to relocate away from the study site to a location that does not have an Anal Cancer/HSIL Outcomes Research (ANCHOR) study site during study participation
Growth factors: all colony forming growth factor(s) have been discontinued for at least one week prior to enrollment (filgrastim, sargramostim, and erythropoietin); for patients on long acting growth factors, the interval should be two weeks
Patients with neurological deficits that are stable for a minimum of one week prior to registration
Patients who require enzyme inducing anti-convulsants to control seizures
Patients with cataracts on ophthalmologic examination
Patient must have relapsed or refractory myeloma that fits or did fit International Myeloma Working Group (IMWG) diagnostic criteria for symptomatic myeloma (although new or worsening end organ damage is not required to be eligible) as defined below:* Presence of clonal bone marrow plasma cells* Presence of serum and/or urinary measurable monoclonal protein or light chains* Evidence of any end organ damage criteria listed below (at any time) attributed to the patient�s myeloma:** Hypercalcemia: serum calcium > 11.5 mg/dL or** Renal insufficiency: serum creatinine > 2 mg/dL** Anemia > 2 g/dL below the lower limit of normal or a hemoglobin value < 10 g/dL** Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
Patients must have been previously treated with an immunomodulatory drug (IMiD) and proteasome inhibitor, must be refractory to carfilzomib defined as progression on or within 2 months of a carfilzomib-containing therapy, and must be progressing
Both men and women of all races and ethnic groups are eligible for this study
Patients must be able to avoid direct contact with pregnant or nursing women, infants and immunocompromised individuals during the days of reolysin treatment and for two days after
Patients must agree not to donate blood, sperm/ova during the course of taking protocol therapy and for at least 4 weeks after stopping treatment
Patients previously treated on clinical trial with reolysin
Patients with a currently active second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation
Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes (POEMS) syndrome
Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug
* For patients who underwent initial surgery and received adjuvant chemotherapy** Triple negative breast cancer (TNBC) patients must have been axillary node-positive (>= pN1, any tumor size) or axillary node negative (pN0) with invasive primary tumor pathological size > 2 cm (>= pT2)** Estrogen receptor (ER) and/or progesterone receptor (PgR) positive/human epidermal growth factor receptor (HER) 2 negative patients must have had >= 4 pathologically confirmed positive lymph nodes* For patients who underwent neoadjuvant chemotherapy followed by surgery** TNBC patients must have residual invasive breast cancer in the breast and/or resected lymph nodes (non-pathological complete response [pCR])** ER and/or PgR positive/HER2 negative patients must have residual invasive cancer in the breast and/or the resected lymph nodes (non-pCR) AND a clinical pathologic stage (CPS) & estrogen receptor status nuclear grade (EG) score >= 3
Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the two following phenotypes:* TNBC defined as:** ER and PgR negative defined as immunohistochemistry (IHC) nuclear staining < 1%** HER2 negative (not eligible for anti-HER2 therapy) defined as:*** IHC 0, 1+ without in situ hybridization (ISH) OR *** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR *** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)* ER and/or PgR positive, HER2 negative breast cancer defined as:** ER and/or PgR positive defined as IHC nuclear staining >= 1%; AND** HER2 negative (not eligible for anti-HER2 therapy) defined as:*** IHC 0, 1+ without ISH OR*** IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR*** ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells (without IHC)
Patients with multifocal or multicentric invasive disease are eligible as long as all the lesions for which HER2 characterization is available are HER2 negative
Patients with synchronous bilateral invasive disease are eligible as long as all the lesions assessed for HER2 on both sides are negative
In both the above cases, the lesion considered at highest risk for recurrence based on the investigator's discretion will be used for eligibility determination
Documented germline mutation in BRCA1 or breast cancer 2, early onset (BRCA2) that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function); local germline (g)BRCA testing results, if available, will be used for establishing eligibility; if local gBRCA testing results are not available, central testing will be provided for those patients who otherwise appear to be eligible
Patients with screening ALT/AST or ALP above institutional upper limit of normal should have liver ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) at any time point between diagnosis of current breast cancer and randomization; screening bone scan is required if ALP and/or corrected calcium level are above the institutional upper limit; (note positron emission tomography [PET]/CT scan may be used as an alternative imaging technique)
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
Involvement in the planning and/or conduct of the study
Patients who do not have deleterious or suspected deleterious gBRCA1 and/or 2 mutations but only have BRCA1 and/or BRCA2 mutations that are considered to be non-detrimental (e.g., �variants of uncertain clinical significance� or �variant of unknown significance� or �variant, favor polymorphism� or �benign polymorphism� etc.)
Previous randomization in the present study
Evidence of metastatic breast cancer; patient considered at high risk of having disseminated disease (i.e. those with locally advanced disease, clinical N2-3 or pathological N1-3 with the exception of pN1a in adjuvant patients) should have a CT/MRI scan of the thorax/abdomen/pelvis or any other area as clinically indicated and a bone scan or a CT scan with bone windows at any point between diagnosis of the current breast cancer and randomization to rule out metastatic breast cancer; (note PET/CT scan may be used as an alternative imaging technique and precludes the need for bone scan); patients with screening ALT/AST or ALP above institutional upper limit of normal should have liver ultrasound, CT or MRI at any time point between diagnosis of current breast cancer and randomization; screening bone scan is required if ALP and/or corrected calcium level are above the institutional upper limit; (note PET CT scan may be used as an alternative imaging technique)
Whole blood transfusions in the last 120 days prior to entry to the study which may interfere with gBRCA testing (packed red blood cells and platelet transfusions are acceptable)
Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index* �Favorable� genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above* �Unfavorable� genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)* Only patients with MYCN non-amplified tumors are eligible for this study
Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:* Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin* Patients with non-adrenal primaries are eligible, but must have positive uptake on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites (urine or serum) to support the diagnosis of neuroblastoma* No prior tumor resection or biopsy
Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes* Group A1:** > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR** Patients less than 6 months of age with an adrenal primary tumor > 3.1 and < 5 cm in greatest diameter OR** < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter* Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in greatest diameter.
Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:* No life threatening symptoms or no impending neurologic or other organ function compromise (e.g. epidural or intraspinal tumors with existing or impending neurologic impairment, periorbital or calvarial-based lesions with existing or impending cranial nerve impairment, anatomic or mechanical compromise of critical organ function by tumor [abdominal compartment syndrome, urinary obstruction, etc.]); horner syndrome is not considered neurologic compromise* No prior tumor resection, tumor biopsy ONLY* Only patients with both favorable histology and favorable genomic features will remain on study as part of Group B; the institution will be notified of histologic and genomic results within 3 weeks of specimen submission on ANBL00B1 or APEC14B1
Patients with MYCN amplified tumors are not eligible
Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study
No known history of severe hypersensitivity reactions to any of the components of efatutazone or paclitaxel formulations
Patients with diabetes mellitus requiring concurrent treatment with insulin or thiazolidinedione (TZD) oral agents are not eligible
Patients with known hypersensitivity to any TZD oral agents are not eligible
Although they will not be considered formal eligibility (exclusion) criteria, physicians should recognize that the following may seriously increase the risk to the patient entering this protocol:* Psychiatric illness which would prevent the patient from giving informed consent* Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient* Patients with a �currently active� second malignancy other than non-melanoma skin cancers; patients are not considered to have a �currently active� malignancy if they have completed therapy and are free of disease for >= 3 years; there is an exception for patients with a history of well differentiated thyroid cancer that has progressed to anaplastic thyroid cancer* Patients who cannot swallow oral formulations of the agent(s)* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study ; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)* Efatutazone is metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), and inhibits CYP2C8, 2C9, 2C19, and 3A4, and is a substrate of P-glycoprotein (PgP) and breast cancer resistance protein (BCRP)
All metastases not resected must be amenable to SBRT
The patient must meet ONE of the three following criteria:* 3-4 radiographically distinct metastases of any distribution in the allowed anatomical sites OR* 2 radiographically distinct metastases that must be anatomically close (i.e., with less than or equal to 5 cm of normal tissue between them) OR* 3 or 4 distinct metastasis, 2 or 3 to be treated with SBRT and the other (s) having been surgically removed
Evaluation by a medical oncologist within 45 days prior to study registration
The following imaging workup to document metastases within 45 days prior to study registration: * Computed tomography (CT) scans of the chest, abdomen and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT
Progression of primary tumor site (breast, prostate, or lung) at time of registration
Metastases with indistinct borders making targeting not feasible
Metastases located within 3 cm of the previously irradiated structures:* Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)* Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)* Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)* Brain stem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)* Whole lung previously irradiated with prior volume 20 Gy (V20Gy) > 30% (delivered in =< 3 Gy/fraction)* Primary tumor irradiated with SBRT* Metastasis irradiated with SBRT
Patients must have newly diagnosed T-lymphoblastic leukemia (T-ALL) or T-lymphoblastic lymphoma (T-LLy) stages II-IV * Note: a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a, and are present either in peripheral blood or > 25% in the bone marrow; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including terminal deoxynucleotidyl transferase (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory* For T-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-LLy defined by the submitting institution will be accepted
Patient has hypersensitivity to bortezomib, boron, or mannitol
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and within 30 days of any dose of bortezomib
Patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell are not eligible; receptor status may be based on any time during treatment prior to study randomization, and from any site (i.e. primary, recurrent, or metastatic)
Pre/peri- and postmenopausal women and all men are eligible for this trial; postmenopausal is defined as:* Age >= 55 years and one year or more of amenorrhea* Age < 55 years and one year or more of amenorrhea, with estradiol < 20 pg/ml* Age < 55 with prior hysterectomy but intact ovaries, with estradiol < 20 pg/ml* Prior bilateral oophorectomyNOTE: Women who do not fit the criteria for being postmenopausal as above are deemed pre-or peri-menopausal; pre/perimenopausal women and all men can enroll provided they agree to receive concomitant luteinizing hormone-releasing hormone (LHRH) agonist; pre/perimenopausal women must have commenced treatment with LHRH agonist at least 4 weeks prior to randomization; if patients have received alternative LHRH agonist prior to study entry, they must switch to goserelin for the duration of the trial
Patients may be treated with bone modifying agents such as bisphosphonates or RANK-ligand agents (e.g. denosumab) per American Society of Clinical Oncology (ASCO) guidelines; whenever possible, patients requiring bone modifying agents should start treatment >= 7 days prior to study therapy and should continue the same agent throughout study unless clinically compelled to change
Patients must have no known allergies to exemestane, entinostat, or medications that have a benzamide structure (e.g., tiapride, remoxipride, clebropride)
Patients with known hypersensitivity to temozolomide or dacarbazine are not eligible
Both men and women of all races and ethnic groups are eligible for this trial
Patient must have 1 lesion with a maximum AXIAL diameter of 12 cm; up to 3 satellite lesions are permitted; satellite lesions, are defined as lesions less than 2 cm that are within 1 cm of the periphery of the dominant lesion (GTV) are permitted; the satellite lesions are NOT included in the AXIAL diameter measurement; regional lymph node involvement within the porta hepatis (as medial as superior mesenteric vein [SMV] portal vein confluence) is permitted if nodes are deemed clinically positive (i.e. fludeoxyglucose F 18 [FDG] avid)
Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:* History/physical examination within 30 days prior to registration * Assessment by medical oncologist who specializes in treatment of IHC within 30 days of registration * Pre-randomization scan (REQUIRED for all patients): computed tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan within 30 days prior to registration; if CT contrast is contraindicated, CT chest without contrast and magnetic resonance imaging (MRI) of abdomen and pelvis is permitted
Negative beta human chorionic gonadotropin (bHCG) within 14 days prior to study entry if patient is pre or perimenopausal
Multiple lesions that don�t meet the criteria as satellite lesions
Extrahepatic metastases or malignant nodes beyond the periportal region; celiac, pancreaticoduodenal and para-aortic nodes > 2 cm are ineligible; note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
Maximum diameter exceeding 12 cm (maximum diameter does not include satellite lesion)
Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to study entry
Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
Direct tumor extension into the stomach, duodenum, small bowel or large bowel
Participants who require anticoagulation should receive low-molecular weight or standard heparin and not warfarin
Patients must have staging scans with abdominal/pelvic computed tomography (CT) or magnetic resonance imaging (MRI) scan and CT scan or x-ray of the chest within 56 days prior to registration; if alkaline phosphatase is above the treating institution�s upper limit of normal (ULN), presence of suspicious bone pain, or if other clinical suspicion, a whole body bone scan is required within 56 days prior to registration
Patients must not be known to have hypersensitivity to cisplatin, gemcitabine (gemcitabine hydrochloride), doxorubicin (doxorubicin hydrochloride), vinblastine (vinblastine sulfate), methotrexate or filgrastim/pegfilgrastim
Patients must agree to participate in the translational medicine studies
Patients must be offered the opportunity to participate in the ultra pure Circulating Tumor Cells (upCTCs) study
ARM I ONLY: For patients with presumed localized disease (any T, N0, M0), a multiparametric MRI (standard of care at the National Institutes of Health [NIH] Clinical Center) must be performed within 4 months of the 18F-DCFBC injection with findings suggestive for prostate cancer and a prostate lesion at least 6 mm or greater; must have histopathologic confirmation of prostate cancer prior to 18F-DCFBC imaging
ARM II ONLY: For patients status post prostatectomy, a PSA >= 0.2 ng/ml
ARM II ONLY: Nonspecific or no evidence for disease on standard imaging modality
ARM III ONLY: Patients must have identifiable metastatic disease on at least 1 clinically indicated imaging modality; if only soft tissue metastasis, one lesion must measure at least 6 mm or greater; patients must have confirmation of prostate cancer prior to 18F-DCFBC imaging* Note: a patient who is eligible for one arm, subsequently may cross-over into a different arm
Subjects for whom participating would significantly delay the scheduled standard of care therapy
Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results
Subjects with severe claustrophobia unresponsive to oral anxiolytics
Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for protocol procedures
Subjects weighing > 350 lbs. (weight limit for scanner table), or unable to fit within the imaging gantry
Patients must have measurable, supratentorial contrast-enhancing progressive or recurrent glioblastoma or gliosarcoma by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment; patient must be able to tolerate MRIs
Patients may have had treatment for no more than 2 prior relapses
Patients must be undergoing surgery that is clinically indicated as determined by their care providers
Patients must be eligible for surgical resection according to the following criteria:* Part 1 Patients: Expectation that the surgeon is able to resect at least 350 mg of tumor from enhancing tumor and at least 350 mg from non-enhancing tumor with low risk of inducing neurological injury* Part 2 Patients: Expectation that the surgeon is able to resect at least 1000 mg from enhancing tumor and at least 350 mg from non-enhancing tumor with low risk of inducing neurological injury
Patients with controlled diabetes are allowed on study; controlled diabetes is defined as < 130 ml/dL for the sake of this study
Patients must not have evidence of significant hematologic, renal, or hepatic dysfunction
Patients must not have evidence of significant intracranial hemorrhage
Patients with known significant active cardiovascular or pulmonary disease at the time of study entry are ineligible
Patients with known diabetes mellitus which is poorly controlled (defined as hemoglobin A1c [HbA1c] > 7%) are ineligible; subjects with a history of transient glucose intolerance due to corticosteroid administration are allowed in this study if all other inclusion/exclusion have been met
Patients who have initiated treatment with bisphosphonates less than 30 days prior to the first administration of MLN0128 (TAK-228) are ineligible; concurrent bisphosphonate use is only allowed if the bisphosphonate was initiated at least 30 days prior to the first administration of MLN0128 (TAK-228)
For weekly MLN0128 (TAK-228) dose cohorts, patients taking proton pump inhibitors (PPIs) are ineligible unless these patients are able to switch to a histamine (H2) blocker and/or antacid
Patients with known manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228) are ineligible
Patients with diabetes mellitus requiring concurrent treatment with insulin or thiazolidinedione (TZD) oral agents are not eligible
Patients with known hypersensitivity to any TZD oral agents are not eligible
Eligible patients must have histopathologically confirmed myxoid liposarcoma with confirmation of DDIT3 rearrangement
For Dose Expansion Cohort: HCC patients only: HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria; all of the following criteria must be met or a biopsy is required:* Known cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection* Hypervascular liver masses > 2 cm, and either serum alpha-fetoprotein (AFP) > 400 ng/ml* AFP > three times normal and doubling in value in the antecedent 3 months* In the expansion cohort, prior treatment with sorafenib as first-line therapy allowed
HCC patients only: prior regional treatments for liver metastasis are permitted including:* Selective internal radiation therapy such as brachytherapy, cyber knife, radiolabeled microsphere embolization, etc.* Hepatic artery chemoembolization* Hepatic artery embolization* Hepatic artery infusional chemotherapy* Radiofrequency ablation* NOTE: patients must be >= 4 weeks from treatment and show progressive measurable/evaluable disease in the liver after regional therapy or must have measurable disease outside the liver
HCC patients only: Child Pugh class A or B7 liver disease
Known portal hypertension or history of variceal bleeding
Current use of anticoagulation; NOTE: use of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter is allowed
Receiving any medications that prolong the QTc and have a known risk for Torsades de pointes; providers should use caution with drugs with possible increased risk for Torsades de pointes; NOTE: patient will be eligible if they can be taken off these medications prior to initiation of therapy and no less than 4 half-lives of the medication
Current use of certain concomitant medications due to mechanistic-based platelet toxicities from navitoclax: clopidogrel, ibuprofen, tirofiban and other anticoagulants, drugs or herbal supplements that effect platelet function; NOTE: antiplatelet use is prohibited during the use of navitoclax; subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the principal investigator in conjunction with the medical monitor
Underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
Patients must have a new morphologic diagnosis of precursor B cell acute lymphoblastic leukemia (ALL) (non T cell) based on World Health Organization (WHO) criteria; patients with Burkitt's (L3) are excluded; patients with Ph-positive or Ph-like ALL with dasatinib-sensitive mutations or kinase fusions may have relapsed or refractory diagnoses* NOTE: Relapsed/refractory Ph-positive patients or Ph-like patients with dasatinib-sensitive mutations or kinase fusions who have previous exposure to either dasatinib or another 2nd or 3rd generation TKI will begin protocol therapy with Cohort 2: re-induction cycle 1
Patients must have a diagnosis of Philadelphia chromosome negative ALL or Ph chromosome positive ALL by cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); patients will be registered to receive treatment in either Cohort 1 (ph-) or Cohort 2 (Ph+ or Ph-like DSMKF) based on these results; diagnostic specimens must be submitted to the site�s local Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory and results of tests (cytogenetics, FISH or PCR) must confirm Ph status prior to registration; if not already known, breakpoint cluster region- abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) status (p190 or p210) must be evaluated in Ph-positive patients by PCR* For Cohort 2, Ph-like testing is not required specifically for this study; however, to be registered to Cohort 2 under the Ph-like DSMKF criterion, the patient must have a known or presumed activating Ph-like signature and dasatinib-sensitive mutation or kinase fusion, such as: ABL1, ABL2, colony stimulating factor 1 receptor (CSF1R), platelet derived growth factor receptor beta (PDGFRB), platelet derived growth factor receptor alpha (PDGFRA), or fibroblast growth factor receptor (FGFR)s that was otherwise identified as part of normal standard of care; prior to registering any patients with a known or presumed activating Ph-like signature and dasatinib-sensitive mutations or kinase fusions (DSMKF) treating physicians must confirm eligibility with the study chairs via email; the study chairs must respond via email with confirmation of patient eligibility prior to patient registration
Cohort I, Ph-negative Patients Only
It is preferred, but not required, that corticosteroids and hydroxyurea should start only after all diagnostic samples have been obtained; however, if the patient was previously on corticosteroids and/or hydroxyurea, this is allowable provided that the patient still has measurable disease at time of the bone marrow aspirate* Corticosteroids and/or hydroxyurea, as well as any of the other therapies mentioned (with the exception of IV cyclophosphamide), may continue to be administered, at physician discretion, until 1 day prior to blinatumomab administration** IV cyclophosphamide must be discontinued at least 7 days prior to blinatumomab administration
Patients must not have testicular involvement; if clinical or ultrasound findings are equivocal, biopsy must be performed; all tests for establishing testicular involvement must be completed within 14 days prior to registration
Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan or magnetic resonance imaging (MRI) of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration
Patients must have specimens submitted for blinatumomab immunogenicity assessment; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to LabConnect
Cohort 2, Ph-positive and Ph-like DSMKF Patients Only
Patients must not be receiving any proton pump inhibitors at the time of registration
Patients must agree to have specimens submitted for blinatumomab immunogenicity testing if subsequently moved to a blinatumomab containing treatment regimen on protocol
Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to the site�s preferred CLIA-approved cytogenetics laboratory; BCR-ABL status must be verified in Ph-positive patients by FISH, cytogenetics, and/or PCR prior to enrollment; if a patient is Ph-positive, PCR for both p190 and p210 must be sent
Patients must be offered participation in specimen submission for future research; with patient�s consent, specimens must be submitted as outlined
COHORT 1 PH-NEGATIVE PATIENTS ONLY: Patients must have achieved CR or CRi within 2 cycles of induction/re-induction with blinatumomab* NOTE: day 1 of post-remission = day 43 of the preceding cycle (+/- 3 days)
COHORT 2 PH-POSITIVE AND PH-LIKE DSMKF PATIENTS ONLY: Newly diagnosed Ph+, newly-diagnosed Ph-like DSMKF, and relapsed/refractory Ph+ patients without prior dasatinib or other 2nd or 3rd generation TKI therapy, must have achieved CR or CRi within 1 cycle of induction with dasatinib/prednisone, or within 2 cycles of re-induction with blinatumomab; relapsed/refractory Ph+ or Ph-like DSMKF patients with prior dasatinib or other 2nd or 3rd generation TKI therapy must have achieved CR or CRi within 2 cycles of re-induction therapy with blinatumomab* NOTE: day 1 of post-remission = day 85 of the preceding induction cycle (+/- 3 days), or day 43 of the preceding re-induction cycle (+/- 3 days) as applicable
Patients must be registered to Step 2 within 28 days after count recovery; (Note: there is no maximum allotted time period for count recovery, providing patient remains in CR or CRi)
A diagnostic contrast-enhanced magnetic resonance imaging (MRI) (no other scan type allowed) of the brain must be performed postoperatively; the residual enhancing tumor and/or resection cavity must have a maximal diameter of 5 cm or less; the tumor diameter will be the greatest diameter as measured on the contrast-enhanced postoperative MRI and will include residual disease and/or the postoperative surgical cavity as appropriate* The postoperative brain MRI should be obtained within 72 hours of resection; if it is not obtained within 72 hours post-resection, then an MRI obtained 2 weeks or longer after surgery is required and can be utilized to ensure maximal diameter of residual tumor and/or resection cavity is 5 cm or less* For cases where a gross total resection of enhancing tumor is performed, but postoperative surgical cavity is NOT identifiable, the patient will be excluded from the trial
The tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed)
As of Amendment 2, if the registering site is a photon center (registering patients to group I), the patient must agree to participate in the advanced imaging sub-study
Recurrent or multifocal malignant gliomas
Any site of distant disease (for example, drop metastases from the GBM tumor site)
Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
Patents treated on any other therapeutic clinical protocols within 30 days prior to step 2 registration
Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker, or severe claustrophobia)
Postoperative tumor plus surgical bed size exceeds 5 cm in maximum diameter
RAI-refractory disease on structural imaging, defined as any one of the following:* A metastatic lesion that is not radioiodine-avid on a diagnostic radioiodine scan performed prior to enrollment in the current study, or* A radioiodine-avid metastatic lesion which remained stable in size or progressed despite radioiodine treatment 6 months or more prior to entry in the study; there are no size limitations for the index lesion used to satisfy this entry criterion* The presence of at least one fluorodeoxyglucose (FDG) avid lesion
COHORT A: Patients must have progressive disease, defined as the presence of new or growing lesion(s) on radiologic imaging within 14 months of study enrollment and/or new/worsening disease related symptoms within 14 months of study enrollment; (progression according to RECIST v 1.1 criteria is not required)
Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone)
Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration; those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been cleared after the last intravenous contrast administration
Patients enrolled in the expansion cohort must have biopsiable disease; there will be preferential enrollment of patients with pancreatic neuroendocrine tumors or ovarian cancer during the dose expansion cohort
Have initiated treatment with bisphosphonates less than 30 days prior to the first administration of MLN0128 (TAK-228); concurrent bisphosphonate use is only allowed if the bisphosphonate was initiated at least 30 days prior to the first administration of MLN0128 (TAK-228)
Concurrent use of herbal supplements and other non-traditional medications; all herbal supplements and other non-traditional medications must be stopped before time of registration
Evidence of any significant intracranial hemorrhage, as determined by the treating investigator, within 6 weeks from registration or as seen on most recent MRI prior to screening/baseline MRI
History of any of the following within 6 months prior to start of MLN0128:
Significant ST depression of >= 1.5 mm in 2 or more leads and/or T wave inversions in >= 2 leads
Complete left bundle branch block
Right bundle branch block + left anterior hemiblock (bi-fascicular block)
Requirement of inotropic support (excluding digoxin)
History or presence of clinically significant ventricular or atrial tachyarrhythmias, or cardiac arrest
Clinically significant resting bradycardia
Presence of unstable atrial fibrillation (ventricular response > 100 beats per minute)
Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
History of arrhythmia requiring an implantable cardiac defibrillator
Angina pectoris =< 12 months prior to starting drug
Placement of a pacemaker for control of rhythm
Pulmonary embolism
Use of hematopoietic colony-stimulating growth factors (e.g. filgrastim [G-CSF], sargramostim [GMCSF], lanimostim [M-CSF]) =< 2 weeks prior to starting study drug; erythropoietin, darbepoetin and erythropoietin-biosimilars are allowed for as long as they have been initiated at least 2 weeks prior to study enrollment
Pulmonary hypertension
Participants with poorly controlled diabetes mellitus (defined as hemoglobin A1c [HbA1c] > 7%); subjects with a history of transient glucose intolerance due to corticosteroid administration are allowed in this study if all other inclusion/exclusion criteria are met
Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
Evidence of bleeding diathesis or coagulopathy
Patients must have had histologic verification of malignancy at original diagnosis or relapse* Parts A & C: patients with recurrent or refractory solid tumors, without central nervous system (CNS) tumors or known CNS metastases, are eligible; note: CNS imaging for patients without a known history of CNS disease is only required if clinically indicated* Part B1: patients with relapsed or refractory neuroblastoma* Part B2: patients with relapsed or refractory osteosarcoma* Part B3: patients with relapsed or refractory rhabdomyosarcoma* Part B4: patients with relapsed or refractory Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET)* Part B5: patients with relapsed or refractory Hodgkin lymphoma* Part B6: patients with relapsed or refractory non-Hodgkin lymphoma* Part B7: patients with unresectable melanoma or metastatic melanoma or relapsed melanoma or refractory melanoma* Part B8: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without Response Evaluation Criteria in Solid Tumors [RECIST] measurable lesion)* Once the dose-escalation portion of Part A is completed, cohorts that are open concurrently for eligible patients (including Parts B and C and potential pharmacokinetic [PK] expansion cohorts) may be selected at the treating physician�s discretion pending slot availability; in the event a disease group cohort in Part B is completed after the initial stage of Simon�s optimal two-stage design, for selected disease cohorts, a corresponding cohort in the same disease group for select disease types will be open in Part D:* Part D1: Patients with relapsed or refractory neuroblastoma* Part D2: Patients with relapsed or refractory osteosarcoma* Part D3: Patients with relapsed or refractory rhabdomyosarcoma* Part D4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET * Part D5: Patients with relapsed or refractory non-Hodgkin lymphoma* Part D6: Patients with relapsed or refractory neuroblastoma (MIBG evaluable disease without RECIST measurable lesion)* Part E3: Patients with relapsed or refractory rhabdomyosarcoma* Part E4: Patients with relapsed or refractory Ewing sarcoma or peripheral PNET
Serum lipase =< ULN at baseline; patients with glucose intolerance should be on a stable regimen and be monitored
Patients with a history of any grade autoimmune disorder are not eligible; asymptomatic laboratory abnormalities (e.g. antinuclear antibody [ANA], rheumatoid factor, altered thyroid function studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder
Patients with >= grade 2 hypothyroidism due to history of autoimmunity are not eligible; note: hypothyroidism due to previous irradiation on thyroidectomy will not impact eligibility
Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from Hodgkin lymphoma (HL)
Patients with nodular lymphocyte-predominant HL
Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
ELIGIBLE SITES:* Extremities: upper (including shoulder) and lower (including hip)* Trunk: body wall
INELIGIBLE SITES: Head and neck, visceral organs (with the exception of embryonal sarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines of the bony pelvis
One of the following chemosensitive histologies as defined in the World Health Organization (WHO) classification of soft tissue tumors (with some evidence of good response to chemoradiation and of sufficient high risk of metastases, or clear evidence of metastases):* Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called �undifferentiated soft tissue sarcoma� or �soft tissue sarcoma not otherwise specified [NOS]�)* Synovial sarcoma* Angiosarcoma of soft tissue* Adult fibrosarcoma* Mesenchymal (extraskeletal) chondrosarcoma* Leiomyosarcoma* Liposarcoma (excluding myxoid liposarcoma)* Undifferentiated pleomorphic sarcoma* Embryonal sarcoma of the liver
Patients with the following histologies are only eligible for the chemotherapy cohort and cannot enroll on the non-chemotherapy cohort:* Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called �undifferentiated soft tissue sarcoma� or �soft tissue sarcoma NOS�) in patients < 30 years of age* Synovial sarcoma* Embryonal sarcoma of the liver
Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: patients aged > 17 years with excess of 2.5 mL of hemoptysis are not eligible)
Patients with gross total resection of the primary tumor prior to enrollment on ARST1321 are NOT eligible; patients who have experienced tumor recurrence after a gross total tumor resection are NOT eligible
CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; Note: the use of fentanyl is permitted
Certain medications that are associated with a risk for QTc prolongation and/or Torsades de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible
Patients must have lactate dehydrogenase (LDH) obtained within 28 days prior to registration in order to obtain baseline stratification information
Patients must have dermatology exam obtained within 28 days prior to registration to obtain baseline measurement; exam to be performed by treating physician or designated dermatologist
Patients must be offered the opportunity to participate in specimen banking
After completing one cycle of therapy, patients will be registered for randomization between intermittent and continuous dosing, provided that they were eligible for the initial step 1 registration and satisfy the following criteria
Patients must not have unequivocal disease progression (by RECIST v1.1) during the first cycle; patients must have disease assessed using the same method as baseline within +/- 5 days of the day 56 scheduled assessment (between days 51-55 of cycle 1, or days 1-5 of cycle 2); all disease must be assessed and documented on the follow-up tumor assessment form (RECIST 1.1)
Patients must be registered to step 2: randomization within +/- 5 days of starting cycle 2; patients MUST NOT be registered prior to the day 56 disease assessment
Patient must be able to tolerate a major surgical procedure based on clinical evaluation, status of their cancer, and any other underlying medical problems
A member of the patient�s surgical team must indicate equipoise for the benefit of the surgical treatment for MBO; the surgeon must respond �Yes� to each of the following questions and sign the S1316 Surgical Equipoise Documentation form for the patient to be eligible:* Is surgery for treatment of malignant bowel obstruction (MBO) being considered for this patient?* Do you have equipoise? if the treating team finds that an operation is required (e.g., for acute abdomen), or they would not offer the patient an operation (e.g., patient is too weak to tolerate surgery), then there is no equipoise
Patients must not have signs of bowel perforation necessitating surgery or �acute� abdomen evidenced by peritonitis on physical exam within 2 days prior to registration
Patients must be registered to the study within 3 working days after being seen by surgical team for MBO or within 3 working days after completion of indicated treatment (e.g. total parenteral nutrition [TPN], anticoagulation reversal) to make them eligible for surgical intervention, whichever is later, and prior to any treatment (surgical or non-surgical) for MBO; treatment is defined as any medication or invasive interventions beyond nasogastric decompression, hydration, pain medications or antiemetic medications; NOTE: somatostatin analogues may be used prior to registration if that use is limited to not more than the two days just prior to registration
Radiographic confirmation of MBO is required prior to registration; scans may have been done before or after admission; scans done prior to admission must have been completed within 14 days prior to admission; computed tomography (CT) scans are preferred
Serum albumin must be planned to be collected after admission, but prior to treatment
Patients must be able to complete the study questionnaires in English or Spanish
Patients must consent and provide both their contact information and that of their representative for a monthly 24-hour dietary recall phone call to be conducted by the Arizona Diet, Behavior and Quality of Life Assessment Lab
Non-pregnant and non-lactating
No history of cornea abnormalities
Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment; tumor may have originated in any primary site* NOTE: in rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established; this would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels [HCG >= 500; AFP >= 500] and typical pattern of metastases)
Must have evidence of progressive or recurrent GCT (measurable or non-measurable) following one line of cisplatin-based chemotherapy, defined as meeting at least one of the following criteria:* Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for adjuvant treatment after macroscopically complete resection of viable GCT is not allowed); in the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for the study* Consecutive elevated serum tumor markers (HCG or AFP) that are increasing; increase of an elevated lactate dehydrogenase (LDH) alone does not constitute progressive disease* Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase
No prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process; only one cycle is allowed
No concurrent treatment with other cytotoxic drugs or targeted therapies
Must have adequate recovery from prior surgery (e.g., healed scar, resumption of diet, etc.)
No late relapse with completely surgically resectable disease; patients with late relapses (defined as relapse >= 2 years from the date of completion of the last chemotherapy regimen) whose disease is completely surgically resectable are not eligible; patients with late relapses who have unresectable disease are eligible
No secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression
Patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive* NOTE: Any patient with BRAF V600 mutant melanoma (whether cutaneous, acral or mucosal primary) who meets the eligibility criteria is eligible for participation in this trial; patients with uveal melanoma are not eligible for this trial
Serum lactate dehydrogenase (LDH) < 10 X ULN (patients with LDH > 10 X ULN are felt to have aggressive disease and should be considered for BRAF inhibitor therapy off protocol), obtained within 4 weeks prior to randomization
Patients must not have malabsorption, swallowing difficulty, or other conditions that would interfere with the ingestion or absorption of dabrafenib or trametinib
STEP 2 (CROSSOVER ARM FOR PATIENTS WITH PROGRESSIVE DISEASE)
The patient must have met all eligibility criteria (except as detailed below) at the time of crossover* RECIST defined measurable disease is not required* Only prior systemic therapy as part of step 1 is allowed; patients who received allowed systemic therapy in the adjuvant setting prior to Step 1 and were eligible for Step 1 are not excluded from proceeding to Step 2 if they meet other eligibility criteria* Malabsorption, swallowing difficulty, or other conditions that would interfere with the ingestion or absorption of dabrafenib or trametinib, or history of retinal vein occlusion are acceptable for patients crossing over to ipilimumab + nivolumab treatment* History of autoimmune disease, excluding interstitial lung disease or pneumonitis, is allowed in patients crossing over to dabrafenib/trametinib therapy* Patients crossing over from nivolumab/ipilimumab to dabrafenib/trametinib who underwent surgery or SRS to CNS metastases need not be off of steroids to start treatment * There is no restriction on serum LDH at crossover* Patients with a history of cardiovascular risks that developed during step 1 of therapy should be discussed with study principal investigator (PI) at time of crossover
Patients must have normal organ and marrow function as defined below, independent of growth factor or transfusion support; patients should not receive growth factors or transfusions for at least 7 days prior to first dose of study drug, with the exception of pegylated granulocyte-colony stimulating factor (G-CSF) (pegfilgrastim) and darbepoetin which require at least 14 days prior to screening and randomization
Female patients who are of non-reproductive potential (i.e., post-menopausal by history - no menses for >= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy) must have a negative serum pregnancy test upon study entry
Patients who are allergic to micafungin and/or voriconazole or any of their ingredients
Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
Presence of transfusion-dependent thrombocytopenia
History of prior malignancy, with the exception of the following:
Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
History of stroke or intracranial hemorrhage within 6 months prior to enrollment
Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator�s opinion, could compromise the patient�s safety, or put the study at undue risk; patients with suspicious radiologic evidence of aspergillosis infection (i.e., chest computed tomography [CT] and/or brain magnetic resonance imaging [MRI]) will not be eligible unless confirmatory laboratory testing of beta-D glucan and aspergillus antigen are negative
Concomitant use of warfarin or other vitamin K antagonists within the last 28 days
Known bleeding disorders (e.g., von Willebrand�s disease) or hemophilia
Unwilling or unable to participate in all required study evaluations and procedures
Currently active, clinically significant hepatic impairment (>= moderate hepatic impairment according to the National Cancer Institute (NCI)/Child Pugh classification
A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis; * Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification
Number of allowable metastases:* =< 4 metastases seen on standard imaging within 60 days prior to registration when all metastatic disease is located within the following sites:** Peripheral lung ** Osseous (bone)** Spine** Central lung** Abdominal-pelvic metastases (lymph node/adrenal gland)** Liver** Mediastinal/cervical lymph node
All known disease amenable to metastasis-directed therapy with either SBRT or resection* NOTE: Symptomatic bone metastasis are allowed if ablative therapy can be delivered* NOTE: Sites for possible surgical excision include lung, liver, adrenal gland, bone, small intestine, large intestine, ovary, and amenable nodal disease sites* NOTE: Surgical stabilization is allowed for a metastasis if it is followed by conventionally fractionated external beam radiotherapy
Maximum diameter of individual metastasis in any dimension =< 5 cm
There are no restrictions on distance between the metastases
The primary tumor site must be controlled prior to registration* For those who present with synchronous primary and oligometastatic disease, primary must be controlled prior to registration* The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preferenceFor those who present with local recurrence and oligometastatic disease, local recurrence must be controlled prior to registration* The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preference
Appropriate stage for study entry based on the following diagnostic workup:* History/physical examination within 60 days prior to registration* Clinical grade computed tomography (CT) scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT within 60 days prior to study registration
Patients with any of the following conditions are NOT eligible for this study.
Pathologic evidence of active primary disease or local/regional breast tumor recurrence at the time of registration;
Metastases with indistinct borders making targeting not feasible* NOTE: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician�s judgment will be required
Metastases located within 3 cm of the previously irradiated structures:* Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)* Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)* Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)* Brainstem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)* Whole lung previously irradiated with prior V20Gy > 30% (delivered in =< 3 Gy/fraction)* Primary tumor irradiated with SBRT* Metastasis irradiated with SBRT
Exudative, bloody, or cytological proven malignant effusions
Pregnancy; lactating females must cease expression of milk prior to signing consent to be eligible
Female and male patients must have histologically confirmed invasive breast cancer that meets the following criteria:* Clinical stage II-III (American Joint Committee on Cancer [AJCC] 7th edition) at diagnosis, based on initial evaluation by clinical examination and/or breast imaging; no metastatic disease allowed* ER- and PR- should meet one of the following criteria:** =< 10% cells stain positive, with weak intensity score (equivalent to Allred score =< 3)** =< 1% cells stain positive, with weak or intermediate intensity score (equivalent to Allred score =< 3)* HER2 negative (not eligible for anti-HER2 therapy) will be defined as:** Immunohistochemistry (IHC) 0, 1+ without in situ hybridization (ISH) HER2/neu chromosome 17 ratio OR** IHC 2+ and ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells OR** ISH HER2/neu chromosome 17 ratio non-amplified with ratio less than 2.0 and if reported average HER2 copy number < 6 signals/cells without IHC** NOTE: patients that originally present with synchronous bilateral tumors are eligible provided both tumors are TNBC, and at least one of them fulfills the remainder eligibility criteria of the protocol; multifocal or multicentric breast cancers are eligible as long as all tumors fulfill eligibility criteria** NOTE: patients that have a discrepancy in ER/PR/HER2 status between original diagnosis and surgical specimen (only applicable if ER/PR/HER2 status were repeated; repeating it is not mandatory) are not eligible for study participation (i.e. ER/PR/HER2 has to fulfill above criteria in both scenarios)
No clinically significant infections as judged by the treating investigator
Young patient age between 12 � 15 could be included in only 6 centers (Bordeaux, Lyon, Villejuif, Lille, Marseille and Paris)
Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
Documented disease progression (as per RECIST v1.1) before study entry; for patients with osteosarcoma, this progression will be confirmed by central review on the basis of two CT scan or magnetic resonance imaging (MRI) obtained at less than 6 months in the period of 12 months prior to inclusion
In accordance with French Regulatory Authorities: Patients with French Social Security in compliance with the French law relating to biomedical research (Huriet Law 88-1138 and related decrees)
Prior treatment with cabozantinib
The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
The subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment
Participation to a study involving a medical or therapeutic intervention in the last 30 days
Prior participation in this study
Patients with colorectal cancer should have failed at least one oxaliplatin-containing regimen
Lesions suspected to be at higher-risk for bleeding such as bowel involvement with tumor that invades into the bowel wall or involves the intraluminal component of bowel by imaging or direct visualization or central pulmonary lesions
Ulcerated skin lesions
Full anti-coagulant therapy Coumadin; patients may be receiving therapeutic Lovenox, Fragmin, or other heparin product that does not require laboratory monitoring
Patients with carcinomatous meningitis should also be excluded
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient�s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
History within 3 months prior to treatment of grade 3-4 gastrointestinal (GI) bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolus, or other uncontrolled thromboembolic event
Patients may have had treatment for an unlimited number of prior relapses
Part 2 (surgical) patients only: patients must be undergoing surgery that is clinically indicated as determined by their care providers; patients must be eligible for surgical resection according to the following criteria:* Expectation that the surgeon is able to resect at least 100 mg of tumor from enhancing tumor and at least 100 mg from non-enhancing tumor with low risk of inducing neurological injury
Patient must not have known sensitivity to terameprocol or any formulation excipients
Patients must not have known impaired cardiac function or clinically significant cardiac disease
Patients must not be on any anticoagulation
Patient must not have prior gastrointestinal (GI) surgery or GI disease that might interfere with the absorption of terameprocol
A single, biopsy-proven SISCCA as defined by the LAST criteria (=< 3 mm depth of invasion, horizontal spread of =< 7 mm, and completely excised with at least 1 mm margin clear of cancer irrespective of the amount of HSIL) documented per investigator assessment in combination with the pathology report within 16 weeks before Segment B enrollment
No evidence of any lymph node spread or distant metastases as determined by positron emission tomography (PET) computed tomography (CT) imaging within 16 weeks of enrollment; alternatively, for those without PET CT capability, a magnetic resonance imaging (MRI) or CT of the abdomen and pelvis and a chest x-ray confirming no evidence of metastatic disease is acceptable
Clinician believes that eradication of concomitant HSIL is reasonable and feasible based on the extent of disease and overall medical condition of the participant
For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current �Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents� and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to enrollment for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment
Prior to Segment B enrollment, participants on combination anti-retroviral therapy (cART) will be required to have a minimum CD4 count of >= 200 and participants not on cART will be required to have a minimum CD4 count of >= 350 to be eligible for the study; participants not currently on cART who have a CD4 count >= 200 and who agree to start cART immediately will be eligible for participation; laboratory data should be obtained within 16 weeks prior to Segment B enrollment
Participants must not have any other concurrent malignancy
Participants must have organ and marrow function within the following parameters within 16 weeks before Segment B enrollment:
Men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment during the study, and for 2 weeks after stopping topical treatment
Participants must, in the opinion of the investigator, be capable of complying with the requirements of this protocol
Anal cancer that cannot be completely excised with a >= 1 mm clear margin from surrounding tissue or where excision to obtain a clear margin would compromise sphincter function or anal canal diameter
The participant�s SISCCA must not have been ablated
Concurrent anal canal or perianal HSIL or condyloma that in the judgment of the clinician cannot be cleared or can only be cleared with undue morbidity to the participant
No prior history of anal cancer, including SISCCA
Ongoing use of anticoagulant therapy other than aspirin or non-steroidal anti-inflammatory drugs (NSAIDS) that cannot be stopped for surgical procedures
Participant plans to relocate away from the study site during study participation
AML patients in first complete remission (CR) (CR1) or first complete remission with incomplete blood count recovery (CRi) after induction and consolidation chemotherapy; except young (< 60 years) AML patients in European LeukemiaNet favorable group; (the current trial will exclude young favorable group AML patients), patients could receive any cycle consolidation or no consolidation per the discretion by the treating physician
Amylase and lipase =< 1.5 x ULN without any symptoms of pancreatitis
All patients will be previously or simultaneously enrolled in the natural history ECD protocol #11-HG-0207, �Clinical and Basic Investigations into Erdheim Chester disease�; eligible patients must have been diagnosed with Erdheim Chester disease, confirmed by pathological evaluation of the affected tissue with adequate staining; affected tissue must harbor the BRAF V600E or V600K mutation
Therapeutic level dosing of warfarin can be used with close monitoring of PT/INR by the site; exposure may be decreased due to enzyme induction when on treatment, thus warfarin dosing may need to be adjusted based upon PT/INR; consequently, when discontinuing dabrafenib, warfarin exposure may be increased and thus close monitoring via PT/INR and warfarin dose adjustments must be made as clinically appropriate; prophylactic low dose warfarin may be given to maintain central catheter patency
Presence of malignancy other than the study indication under this trial within 3 years of study enrollment
Patients with history of rat sarcoma (RAS) mutation-positive tumors are not eligible regardless of interval from the current study; Note: RAS testing and absence of RAS mutation are required for eligibility
Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject�s safety, obtaining informed consent, or compliance with study procedures
Inability to travel to the National Institutes of Health (NIH) Clinical Center
Patients with wild type BRAF gene molecular results on ECD affected tissue
If the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate the PML-RARalpha transcript by RQ-PCR to be eligible
Patients with a history or presence of significant ventricular or atrial tachyarrhythmia are excluded
Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded
Patients must have high grade upper tract urothelial carcinoma proven by one of the following:* Biopsy;* Urinary cytology with a 3-dimensional upper urinary tract mass on cross-sectional imaging; or* Urinary cytology and a mass visualized during upper urinary tract endoscopy
Patients must have no evidence of metastatic disease or clinically enlarged lymph nodes on computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis and CT chest obtained within 28 days of registration (a negative biopsy is required for lymph nodes >= 1 cm in size to confirm lack of involvement); patients with lymph nodes >= 1 cm in whom a biopsy is deemed not feasible are not eligible; patients with elevated alkaline phosphatase or suspicious bone pain should also undergo baseline bone scans to evaluate for bone metastasis
Patients must not have a history of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
Patients with concomitant primaries of the bladder/urethra are allowed, as long as these sites are surgically resected and non-invasive cancers (< cT1N0)
Patients must not have another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer; patients that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment
Lipase and amylase =< 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
Patients who have been previously treated with MET or vascular endothelial growth factor receptor (VEGFR) inhibitors (except for patients on renal cell cancer [RCC] cohort) are not eligible for the expansion cohorts but can enroll in the phase I portion
The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, thrombin or factor Xa inhibitors; aspirin (up to 325 mg/day), low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
For disease specific studies: the subject has had evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment
Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery
Patients with regional node involvement as their only site of disease beyond the primary tumor will not be eligible
Patients whose primary tumors arise in the intra-dural soft tissue (eg. brain and spinal cord) are not eligible
Patients with known pre-existing diabetes mellitus will be excluded from study
Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn�s disease, malabsorption, etc)
Patients must not have any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
Serum amylase =< 1.5 x ULN
Serum lipase =< 1.5 x ULN
Patients with known macular degeneration, uncontrolled glaucoma, or cataracts are not eligible
After completion of all three screening questionnaires, participant must score accordingly on at least one questionnaire to be eligible:* Score >= 8 on the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS)-Anxiety/Depression Scale OR* Score >= 4 on the Distress Thermometer OR* Score > 5 on the Modified Cancer Acceptance Scale
Willing/able to attend brief introductory session and use assigned device for the assigned period of time (15 minutes once or twice per day), at least 5 days per week for 12 weeks
Must have telephone
Patient does not understand English
Any change in psychotropic medications in past 30 days
Hearing loss that would preclude participating in interventions; adequate hearing to participate will be determined via: (1) response of �no� to the question [�Do you have a hearing problem now?�]; participants with hearing aids will be allowed to enroll as long as their hearing is adequate to hear the sounds on the study devices; if necessary, potential study participants will receive a brief test trial with the RESPeRATE device; if they indicate inability to hear the guiding tones, they will not be enrolled in the study
CORTISOL EXCLUSION: Participants with endocrine disorders (e.g., diabetes and thyroid disorders) or on steroid-based medications are excluded from the cortisol portion of the study (with the exception of topical hydrocortisone that is permitted)
Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer with documented disease progression (disease not amendable to curative therapy); histologic confirmation of the original primary tumor is required via the pathology report; NOTE: patients with mucinous histology are NOT eligible; patients with carcinosarcoma histology are NOT eligible
Patients must have at least one �target� lesion to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as �non-target� lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Adequate thyroid function within 28 days prior to registration defined as serum thyroid-stimulating hormone (TSH) in normal range
Platinum-free interval (PFI) - patients must have progressed < 12 months after completion of their last platinum-based chemotherapy; the date (platinum free interval) should be calculated from the last administered dose of platinum therapy to documentation of progression
Adequate oxygen saturation via pulse oximeter within 28 days prior to registration (i.e., patient can NOT have CTCAE hypoxia grade 2 or greater)
No prior carboplatin unless given in neoadjuvant/adjuvant setting for curative intent and more than 6 months have elapsed since last carboplatin dose; in the case of relapsed ovarian cancer, patients are eligible if more than 6 months have elapsed since last carboplatin dose
Anticoagulation and anti-platelet therapies are not permitted (this includes Coumadin, low molecular weight heparins, factor Xa inhibitors, aspirin and non-steroidal anti-inflammatory drug [NSAIDS] or other medicines with similar effects)
Has a study site-specific nurse available to act as a PN or has a (study site-specific or shared) nurse available to act as a �clinical consultant� to a study site-specific, non-nurse navigator* Study sites randomized to the Intervention Arm are not eligible to register subjects (nor administer the protocol intervention), until the site�s identified PN(s) has/have completed the protocol-specific navigation training
STUDY PARTICIPANT ELIGIBLITY:
African American or Black race
Recently diagnosed (i.e., within 70 days of enrollment) with clinically suspicious or biopsy-proven early stage (i.e., stage I-II) NSCLC; the inclusion criteria will be operationalized as follows:* Recently diagnosed (i.e., within 70 days of definitive tissue biopsy) biopsy-proven NSCLC* Recently diagnosed (i.e., within 70 days of clinical diagnosis) probable NSCLC where probable NSCLC is defined as a suspicious lung nodule for which the patient was referred for** Invasive diagnostic procedure (i.e., bronchoscopy or image-guided biopsy), OR** Surgical or radiation oncology consultation and date of clinical diagnosis is defined as (whichever comes first)** Date of referral for invasive diagnostic procedure (i.e., bronchoscopy or image-guided biopsy), OR** Date of referral for surgical or radiation oncology consultation* Study sites should enroll patients that meet either of the above inclusion criteria as early as possible during the diagnostic work-up (i.e., if the patient meets the criteria for recently diagnosed, clinically suspicious NSCLC, definitive tissue biopsy is not required for eligibility)
Evaluated/treated for NSCLC at an eligible study site
Access to a telephone
Currently in hospice care
Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
More than 2 lines of therapy beyond corticosteroids with or without calcineurin inhibitors or sirolimus
Patients must have known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status of tumor; wild-type (WT) or mutated, prior to randomization
Serum lactate dehydrogenase (LDH) =< 10 X ULN
Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed)
Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of the study drugs hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea; patients must not have an active infection requiring current treatment with parenteral antibiotics
Patients must have a post-gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan and an axial T2/FLAIR sequence; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; this MRI must be obtained =< 21 days prior to step 1 registration
The following baseline neurocognitive assessments must be completed prior to Step 2 registration: HVLT-R, TMT, and COWA; the neurocognitive assessment will be uploaded into the NRG RAVE System for evaluation by Dr. Wefel; once the upload is complete, within one business day a notification will be sent to proceed to Step 2; NOTE: completed baseline neurocognitive assessments can be uploaded at the time of Step 1 registration
Patients who are primary English or French speakers are eligible
Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
Prior allergic reaction to memantine (memantine hydrochloride)
Current alcohol or drug abuse (may exacerbate lethargy/dizziness with memantine)
Patients with definitive leptomeningeal metastases
Contraindication to magnetic resonance (MR) imaging such as implanted metal devices or foreign bodies
Contraindication to gadolinium contrast administration during MR imaging, such as allergy or insufficient renal function
Current use of (other N-methyl D-aspartate [NMDA] antagonists) amantadine, ketamine, or dextromethorphan
Participants may be treatment naive, refractory to or intolerant of one or more prior therapies, or treated with prior systemic treatment including but not limited to liposomal doxorubicin
Participants must have biopsy-proven KS involving skin with or without visceral involvement
Participants must have cutaneous lesion(s) amenable to four (4) 5-mm tumor biopsies during the study (either 4 separate lesions measuring >= 5 mm each OR 2 separate lesions measuring >= 10 mm each) and at least five additional lesions measurable for assessment with no improvement over the past month
If participant is HIV positive, participants must be on a stable antiretroviral regimen for at least 12 weeks prior to study enrollment
There should be no evidence for improvement in KS in the 3 months prior to study enrollment, unless there is evidence for progression of KS in the 4 weeks immediately prior to study enrollment
Participants must, in the opinion of the investigator, be capable of complying with the protocol
Participants for whom front-line cytotoxic therapy is indicated (i.e. symptomatic visceral or pulmonary KS or symptomatic KS impairing functional status)
Previous local therapy of any KS-indicator lesion unless the lesion has clearly progressed since that local treatment; any prior local treatment to indicator lesions regardless of the elapsed time should not be allowed unless there is evidence of clear-cut progression of said lesion
Participants with a recent history (< 6 months) of a major infarct including but not inclusive to bowel ischemia, cerebral vascular accident, transient ischemic attack, myocardial infarction, limb ischemia, or skin necrosis
Participants with a QTcF (Fridericia correction formula) > 480 ms on 2 out of 3 electrocardiograms (EKGs) (if first EKG is < 480, no need to repeat, if first EKG is > 480 repeat twice for a total of 3 EKGs)
Participants with a recent history (< 6 months) of a major bleed which will be defined as a symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a fall in hemoglobin level 2 grams/dL or more, or leading to transfusion of two or more units of whole blood or packed red cells
Participants on any dose of warfarin or are on full dose anticoagulation with other agents including low molecular weight heparin, antithrombin agents, antiplatelet agents and full dose aspirin within 7 days prior to study enrollment; participants on prophylactic doses of low molecular weight heparin are allowed
Participants with diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months, or any other intercurrent medical condition that contraindicates treatment with sEphB4-HSA or places the participant at undue risk for treatment related complications
Physical or psychiatric illness/social situations that in the estimation of the investigator would limit compliance with study requirements or place the participant at high risk of toxicity or non-compliance
Patient must not require the use of full dose coumarin-derivative anticoagulants such as warfarin; low molecular weight heparin is permitted for prophylactic or therapeutic use; factor X inhibitors are permitted* NOTE: Warfarin may not be started while enrolled in the EAY131 study* Stopping the anticoagulation for biopsy should be per site standard operating procedure (SOP)
Patients with controlled diabetes are allowed on study; controlled diabetes is defined as fasting blood sugar (FBS) = 130 mg/dL or less, and patients whose FBS can be brought in this range with medical therapy are eligible for trial inclusion
Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228)
Subjects who have initiated treatment with bisphosphonates less than 30 days prior to the first administration of MLN0128 (TAK-228); concurrent bisphosphonate use is only allowed if the bisphosphonate was initiated at least 30 days prior to the first administration of MLN0128 (TAK-228)
Arm B (first stage of phase II of TRC102 and pemetrexed): patients with malignant pleural or peritoneal mesothelioma who had progressed while being treated with or had recurred within 6 months of being treated with pemetrexed and cisplatin or carboplatin frontline; intervening treatment is allowed
Prior pemetrexed is allowed except Arm A dose level 4 (cisplatin 75 mg/m^2)
No studies have been performed to assess potential metabolic and transport interactions of TRC102; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; the case report form must capture the concurrent use of all other drugs, over-the-counter medications, or alternative therapies
Patients with known disorders associated with hemolysis
Patients with thromboembolic disease and on anticoagulation
Patients with a prior cumulative cisplatin dose > 300 mg/m^2 (pertains to Arm A only)
The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination
All of the following staging criteria (according to the 7th edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual) must be met:* By pathologic evaluation, primary tumor must be pT1-3* By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN2b, pN3a, or pN3b* If pN0, pathological tumor must be >= 3.0 cm
The tumor must have been determined to be human epidermal growth factor receptor 2 (HER2)-negative as follows:* Immunohistochemistry (IHC) 0-1+; or* IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to centromere enumerator probe 17 (CEP17) < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells; or* ISH non-amplified with a ratio of HER2 to CEP17 < 2.0, and if reported, average HER2 gene copy number < 4 signals/cells
The tumor must have estrogen receptor (ER)-and progesterone receptor (PgR)-status assessed using current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines; patients are eligible if the tumor staining meets one of the following criteria:* ER-negative and PgR- negative by ASCO/CAP guidelines, OR* ER or PgR stains are positive in 1-9% of cells and neither is positive in >= 10% of cells
The patient must have undergone either a mastectomy (total, skin-sparing, or nipple-sparing) or lumpectomy
For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist; if pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection)
For patients who undergo mastectomy, the margins must be free of residual gross tumor; (patients with microscopic positive margins are eligible as long as post-mastectomy radiation therapy [RT] of the chest wall will be administered)
The patient must have completed one of the procedures for evaluation of pathologic nodal status listed below.* Sentinel lymphadenectomy alone:** If pathologic nodal staging based on sentinel lymphadenectomy is pN0 or pN1b;** If pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1a and the patient has undergone breast conserving surgery (with planned breast radiotherapy), the primary tumor must be T1 or T2 by pathologic evaluation and the nodal involvement must be limited to 1 or 2 positive nodes* Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; or* Axillary lymphadenectomy with or without SN isolation procedure
Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the study if liver imaging (computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET]-CT, or PET scan) performed within 90 days prior to randomization does not demonstrate metastatic disease and the requirements above are met
Patients with alkaline phosphatase that is > ULN but =< 2.5 x ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT scan, or PET scan performed within 90 days prior to randomization does not demonstrate metastatic disease
Previous therapy with anthracyclines or taxanes for any malignancy
Intrinsic lung disease resulting in dyspnea
History of hospitalization in past 12 months for diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic syndrome (HHNS)
Known hypersensitivity to any of the study drugs or excipients, e.g., polysorbate 80 and Cremophor EL
Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
INCLUSION CRITERIA FOR STRATA A, B, D AND E
Tumor: patient must have one of the following diagnoses to be eligible:
All subjects must have measurable disease in 2-dimensions on MRI scan of the brain; disease should be consistently measured with the two largest perpendicular dimensions
Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment
Patients must be fully recovered from all acute effects of prior surgical intervention
All races and ethnic groups are eligible for this study
Patients with neurological deficits should have deficits that are completely stable for a minimum of 1 week (7 days) prior to enrollment
Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (e.g. filgrastim, sargramostim, erythropoietin); 2 weeks must have elapsed for long-acting formulations
Patients must be willing to use brief courses (at least 72 hours) of steroids as directed for potential inflammatory side effects of the therapy if recommended by their treating physician
EXCLUSION CRITERIA FOR STRATA A, B, D AND E
Patients with bulky tumor on imaging are ineligible; treating physicians are encouraged to contact the study chair to request a rapid central imaging review to confirm fulfilment of these eligibility criteria, if they have concernsBulk tumor is defined as:* Tumor with evidence of clinically significant uncal herniation or midline shift* Tumor with diameter of > 5 cm in one dimension on T2/fluid attenuated inversion recovery (FLAIR)* Tumor that in the opinion of the site investigator, shows significant mass effect in either the brain or spine* Multi-focal/ metastatic disease: Note: A second focus of enhancement in a single FLAIR abnormality is permissible and will not exclude the subject** Patients with multi-focal parenchymal disease are ineligible** Patients with leptomeningeal metastatic disease are eligible* Strata B, D and E � patients whose tumor has a significant component involving the brainstem or with significant fourth ventricular compression are ineligible
Patients with uncontrolled seizures defined as seizures that require regular use of rescue medications or in the opinion of the investigator require increasing doses of anti-epileptic medications or would compromise the ability to tolerate study therapy or interfere with protocol therapy or procedures; patients with seizures that are well controlled are eligible and may be on antiepileptic medications if on a stable dose
INCLUSION CRITERIA FOR STRATUM C: Patients must have a histologically confirmed primary brain tumor that is recurrent, progressive or refractory; inclusion criteria encompasses all types of brain tumors (e.g. gliomas, embryonal tumors or any other type of brain tumor as long as other eligibility criteria are met;* Patients with high-grade gliomas are eligible for this clinical trial at least 2 weeks after completion of radiotherapy independent of tumor progression/recurrence as long as they are not enrolled on any other therapeutic clinical trial and there is macroscopic residual disease* Patients with other concomitant tumors associated with CMMRD syndrome including gastrointestinal polyps/adenomas and carcinomas, lymphomas and leukemias will be eligible as long as they are not requiring anticancer therapy directed against these other cancers and meet all other eligibility criteria
INCLUSION CRITERIA FOR STRATUM C: All subjects must have measurable disease in 2-dimensions on MRI scan of the brain and/or spine; disease should be consistently measured with the two largest perpendicular dimensions
INCLUSION CRITERIA FOR STRATUM C: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment
INCLUSION CRITERIA FOR STRATUM C: Patients must be fully recovered from all acute effects of prior surgical intervention
INCLUSION CRITERIA FOR STRATUM C: All races and ethnic groups are eligible for this study
INCLUSION CRITERIA FOR STRATUM C: Patients with neurological deficits should have deficits that are completely stable for a minimum of 1 week (7 days) prior to enrollment
INCLUSION CRITERIA FOR STRATUM C: Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (i.e. filgrastim; sargramostim; erythropoietin); 2 weeks must have elapsed for long-acting formulations
INCLUSION CRITERIA FOR STRATUM C: Patients must be willing to use brief courses (at least 72 hours) of steroids as directed for potential inflammatory side effects of the therapy if recommended by their treating physician
EXCLUSION CRITERIA FOR STRATUM C: Patients with diffuse intrinsic pontine or other brainstem high-grade glioma and those with primary spinal cord tumors
EXCLUSION CRITERIA FOR STRATUM C: Patients with bulky tumor on imaging are ineligible; treating physicians are encouraged to contact the study chair to request a rapid central imaging review to confirm fulfilment of these eligibility criteria, if they have concerns; bulky tumor is defined as:* Tumor with any evidence of uncal herniation or midline shift* Tumor with diameter of > 5 cm in one dimension on T2/FLAIR* Tumor that in the opinion of the site investigator, shows significant mass effect* Metastatic disease: Patients with =< 5 separate foci of metastatic disease not causing mass effect on adjacent parenchyma and each measuring less than 0.5 cm in maximum diameter will be eligible for this arm of the study; patients with diffuse linear leptomeningeal spread are not eligible for this arm of the study* Multi-focal disease: Patients with multi-focal parenchymal disease will be eligible for stratum C if the sum of the product of the maximum perpendicular diameters of all measurable non-contiguous lesions is less than 16 cm^2; in such cases, a minimum of 2 and a maximum of 5 �target� non-contiguous lesions will be selected; the lower size limit of the target lesion(s) should be at least twice the thickness of the slices showing the tumor to decrease the partial volume effect (e.g., 8 mm lesion for a 4 mm slice)
EXCLUSION CRITERIA FOR STRATUM C: Patients with uncontrolled seizures defined as seizures that require regular use of rescue medications or in the opinion of the investigator require increasing doses of antiepileptic medications or would compromise the ability to tolerate study therapy or interfere with protocol therapy or procedures; patients with seizures that are well controlled are eligible and may be on antiepileptic medications if on a stable dose
Patients with a history of allergic reactions attributed to compounds of similar composition to dolastatin or auristatin (e.g. Auristatin PHE, Auristatin PE, and symplostatin)
Clinical picture indicative of leukostasis or evidence of disseminated intravascular coagulopathy
Acute promyelocytic leukemia (APL, M3)
Major surgical procedures =< 28 days before beginning study treatment or minor surgical procedures =< 7 day before beginning study treatment; no waiting required after placement of a vascular access device
Circulating blast count >= 50,000/uL within the week preceding enrollment
Any of the following related to risk of torsades de pointes and sudden cardiac death:* History of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implanted cardiac defibrillator* Concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia; agents used for rate-control of atrial fibrillation are permitted provided that they are not prohibited due to potential drug interactions* Known congenital long QT syndrome* Second degree atrioventricular (AV) block type II, third degree AV block, or ventricular rate < 50 bpm or > 120 bpm
Any known UGT1A polymorphism, heterozygous or homozygous
Active gastrointestinal (GI) conditions that might predispose to drug intolerance or poor drug absorption
Receiving any other therapies for cancer treatment (with the exception of gonadotropin-releasing hormone [GnRH] agonists for prostate cancer); Note: hydroxyurea is allowed before initiation of study treatment and for the first 5 days of study treatment
Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient�s risk, interfere with the patient�s participation in the study, or hinder evaluation of study results
Thyroid stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH if free T4 is normal and patient is clinically euthyroid, patient is eligible
Re-registration Eligibility Criteria (for patients who crossover from arm 1 nivolumab alone to dual agent nivolumab and ipilimumab upon progression)
Patient MUST have had progressive disease (radiographic or clinical) while on arm 1 single agent nivolumab while registered to A091401
Patients removed from any immunotherapy for reasons other than progressive disease, including arm 1 single agent nivolumab of A091401, are NOT eligible for re-registration
Patients must have completed a minimum of 10 weeks of single agent nivolumab on arm 1 of A091401 to be eligible for re-registration
Patients must have completed study drug on arm 1 of A091401 (i.e., last dose of nivolumab) =< 12 months of re-registration to crossover dual agent therapy
Re-registration: TSH WNL; supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH, if free T4 is normal and patient is clinically euthyroid, patient is eligible
No lytic lesions on skeletal survey and whole body positron emission tomography (PET)/computed tomography (CT) other than a single lesion associated with solitary bone plasmacytoma
No lytic lesions on skeletal survey and whole body PET/CT other than a single lesion associated with solitary bone plasmacytoma within 28 days prior to registration
Participants must have disease that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains or by minimal residual detection; measurable disease is defined as one or more of the following:* Serum M protein > 0.5 G/DL, or* Urine M protein > 200 MG/24H, and/or* Serum free light chain (FLC) assay: involved FLC level > 10 MG/DL with abnormal serum FLC ratio* >= 50 plasma cells detectable by multicolor flow cytometry, at a sensitive level of 10^-4 (determined by central review)
Patients with active HCV infection should be referred for HCV treatment and standard radiotherapy for the plasmacytoma
Known allergy to boron or excipients in the formulation
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of study drugs including difficulty swallowing
Life-threatening illness unrelated to cancer
History of erythema nodosum if characterized by a desquamating rash while taking thalidomide, pomalidomide, or similar drugs
No cardiac arrhythmias within 182 days of registration
Within 90 days prior to registration: Complete dental exam; complete elimination of dental and periodontal pathology including crowns on teeth susceptible to fracture, extraction of non-restorable or periodontally uncorrectable teeth; creation of an oral environment that the patient can efficiently maintain in a high state of health; and oral hygiene instruction to maintain excellent oral health
Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])
There are no minimal organ function requirements for enrollment on this study* Note: Previous cardiac repair with sufficient cardiac function is not an exclusion criteria
Patients with promyelocytic leukemia (French-American-British [FAB] M3)
Patients must not have acute promyelocytic leukemia (APL) and must not have evidence of t(15;17)(q22;q21)
Patients must be able to lie still for a 1.5 hour PET scan
Patient must NOT weigh more than the maximum weight limit for the PET/CT table for the scanner(s) to be used at each center
The patient is participating in the trial at an institution which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined scanner qualification procedures and received ECOG-ACRIN approval as outlined
Dexamethasone dose must be provided for treatment group assignment:* Group A: patients not on dexamethasone or on a dose =< 0.75 mg daily (or equivalent of an alternative corticosteroid)* Group B: patients who require dexamethasone >= 4 mg daily (or equivalent of an alternative corticosteroid)** Patients must have been on the group assignment dose of corticosteroids for at least 5 days prior to the dose of NT-I7; corticosteroid dose changes prior to the start of treatment are allowed as long as they do not alter patient�s group assignment
Patients with known hypersensitivity to NT-I7 or any component used in the vehicle/formulation are ineligible
Patient is a postmenopausal woman, man, or premenopausal woman for whom standard endocrine therapy alone (tamoxifen, aromatase inhibitor [AI], with or without ovarian suppression or fulvestrant) is planned after FES-PET/CT is completed
Medically stable as judged by patient�s physician
Patient must NOT be in liver failure as judged by the patient�s physician
Primary tumor and/or metastatic site must be ER+ and may be progesterone-receptor positive (PgR+) or progesterone-receptor negative (PgR-) by IHC; patients with a history of an estrogen-receptor negative (ER-) primary tumor and a documented ER+ metastatic site are eligible
Patient must be able to lie still for a 20-30 minute PET/CT scan
Patient must NOT weigh more than the maximum weight limit for the table for the PET/CT scanner at the institution where the study is being performed
The patient is participating in the trial at an institution which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined scanner qualification procedures and received ECOG-ACRIN (or current ACRIN) approval
Patients must have at least one measurable PN, defined as a lesion of at least 3 cm measured in one dimension; patients who underwent surgery for resection of a PN are eligible provided the PN was incompletely resected and is measurable as per criteria above; measurability and suitability for volumetric MRI analysis of the target PN must be confirmed with the National Cancer Institute (NCI) Pediatric Oncology Branch (POB) prior to enrolling a patient; the target PN will be defined as the clinically most relevant PN, which has to be amenable to volumetric MRI analysis; PN will be classified as �typical PN� or �nodular PN� versus solitary nodular PN prior to enrollment
The PN must be inoperable, defined as a PN that cannot be surgically completely removed without risk for substantial morbidity due to: encasement of or close proximity to vital structures, invasiveness, or high vascularity of the PN; the PN either causes morbidity or it is growing and has the potential to cause morbidity such as (but not limited to): head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, and lesions of the extremity that cause limb hypertrophy or loss of function or pain; PN growth will be defined as a >= 20% increase in PN volume within approximately 3 years prior to enrollment on this trial
Patients must have a PN amenable to a percutaneous biopsy to participate in the biopsy portion of this study, and must be willing to undergo pre-, and on treatment tumor biopsies; there should be no contraindication for serial biopsies; NOTE: up to 10 patients who meet all criteria, but have PN which cannot be biopsied safely, will be eligible for the treatment portion of the study
Must be able to undergo serial MRI scans for response evaluation
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (patients who are wheelchair bound because of paralysis secondary to a plexiform neurofibroma should be considered ambulatory when they are up in their wheelchair; similarly, patients with limited mobility secondary to need for mechanical support (such as an airway PN requiring tracheostomy or continuous positive airway pressure [CPAP] will also be considered ambulatory for the purpose of the study)
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study
Supplementation with vitamin E greater than 100% of the daily recommended dose
Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol; prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target PN on MRI
Known ophthalmologic conditions, such as:* Current or past history of central serous retinopathy* Current or past history of retinal vein occlusion* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study chair* Subjects with any other significant abnormality on ophthalmic examination should be discussed with the study chair for potential eligibility* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Clinical judgment by the investigator that the patient should not participate in the study
HIV plasma HIV-1 ribonucleic acid (RNA) below detected limit obtained by Food and Drug Administration (FDA)-approved assays (limit of detection: 75) within 4 weeks prior to registration
Participants must be purified protein derivative (PPD) negative; alternatively, the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay can be used; an individual is considered positive for M. tuberculosis infection if the IFN-gamma response to tuberculosis (TB) antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control); the result must be obtained within 12 weeks prior to enrollment; PPD positive (or Quantiferon assay positive) participants are permitted if prophylaxis has been completed prior to enrollment
Participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 12 weeks following enrollment
Participants with clinical or radiographic evidence of pancreatitis are excluded
Criteria for Solid Tumor Expansion and Lymphoma Cohorts:* Inclusion and exclusion criteria for this cohort are the same as above, with the following rule for CD4 count based on tolerability in Phase I; if, participants with lymphocyte T CD4 count between 100-200/mm^3 (Stratum 2) are shown to tolerate treatment in the Phase I dose de-escalation portion at the same dose level as those with CD4 counts > 200/mm^3 (Stratum 1), participants in the expansion cohort with CD4 counts >= 100/mm^3 are permitted; otherwise, the expansion is open to all solid tumor patients except those whose tumors are known not to respond to nivolumab (pancreas, prostate and MSS colon cancer); for the relapsed refractory HIV-cHL cohort, participants with CD4 count >= 100/mm^3 are permitted
Histological documentation of primary adenocarcinoma of the pancreas
Surgically eligible for tumor resection with curative intent
Non ductal adenocarcinomas, neuroendocrine neoplasms, cystic tumors of the pancreas such as cystadenomas, cystadenocarcinomas and solid pseudopapillary neoplasms; in addition, adenocarcinomas arising from duodenum, distal bile duct, and ampulla will also be excluded
Patients with any type of recurrent pancreatic adenocarcinoma
Previous treatment with any other compound that targets CD40
Concurrent treatment with any anticancer agent outside of this protocol
History of deep venous thrombosis or migratory thrombophlebitis (Trousseau)
Hereditary or acquired coagulopathies (e.g., hemophilia, von Willebrand disease, or cancer associated disseminated intravascular coagulation [DIC])
Treatment on another therapeutic clinical trial within 4 weeks of enrollment in this trial
Concurrent or planned concurrent treatment with anticoagulants such as Coumadin or heparin, except to maintain patency of in dwelling catheters
Patients must have relapsed or become refractory to conventional therapy, with a regimen including some combination of high dose methotrexate, doxorubicin, cisplatin, ifosfamide and etoposide; and have had histologic verification of osteosarcoma at original diagnosis or at the time of recurrence
Patients with known sensitivity to any of the products to be administered during the study (eg, mammalian derived products, calcium or vitamin D)
Patients receiving bisphosphonates
Pre-existing conditions* Disorders associated with abnormal bone metabolism* Hypocalcemia that is not corrected with oral calcium supplementation* Vitamin D < 20 mg/mL* Paget�s disease* Prior history or current evidence of osteonecrosis of the jaw* Any dental or oral condition likely to result in disruption of mucosal integrity during denosumab therapy including: active dental or jaw condition requiring oral surgery or tooth extraction; non-healed dental or oral surgery or planned invasive dental procedures during the anticipated course of study therapy* Unstable systemic disease, excluding osteosarcoma, such as unstable proximal renal tubule dysfunction (Fanconi syndrome) or congestive heart failure
Patients with controlled diabetes are allowed on study; controlled diabetes is defined as fetal bovine serum (FBS) =< 130 mg/dL in the context of this study
Patient history:* Patients with history of neurofibromatosis (NF) may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months* No metastatic meningiomas (as defined by extracranial meningiomas) allowed* No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug* No known active hepatitis B or C* No current Child Pugh class B or C liver disease* No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)* No uncontrolled diabetes defined as a known diabetic with hemoglobin A1C (HBA1C) > 7.5 OR fasting glucose > 140* No uncontrolled hypertension defined as blood pressure (BP) > 140/90* No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration
Patients must have a Ki-67 proliferative index of 20-100% OR at least 10 mitotic figures per 10 high powered fields
Patients may not be receiving Coumadin while on treatment; other anticoagulants are allowed
Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency will be excluded
Patients with impaired decision making capacity may participate in the study if a legal authorized representative is available to consent
Patients must NOT have absorption issues that would limit the ability to absorb study agents
Patients with symptomatic peripheral vascular disease are not eligible
Patients must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for the treatment and the protocol
Patients must have platinum-sensitive recurrent high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancers; patients with other (clear cell, mixed epithelial, undifferentiated carcinoma, or transitional cell carcinoma) high-risk histologies are also eligible, provided that the patient has a known deleterious germline BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory; Note: Due to the long acceptance of germline BRCA testing through Myriad, Myriad testing will be accepted; if testing for germline BRCA is done by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) listing the mutation and confirming that the laboratory results showed a recognized germline deleterious BRCA1 or BRCA2 mutation or BRCA rearrangement is required; please collect a copy of Myriad or other BRCA mutational analysis (positive or VUS or negative) reports* Platinum-sensitive disease defined as no clinical or radiographic evidence of disease recurrence for > 6 months (or 182 days) after last receipt of platinum-based therapy* Patients must have had a complete clinical response to their prior line of platinum therapy and cannot have had progression through prior platinum-based therapy
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid stimulating hormone (TSH) within normal limits
Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
Patients may not have received prior treatment affecting the vascular endothelial growth factor (VEGF) pathway (including, but not limited to thalidomide, sunitinib, pazopanib, sorafenib, and nintedanib); bevacizumab used in the upfront setting in conjunction with chemotherapy and/or as maintenance to treat newly diagnosed disease will be allowed
History of stroke or transient ischemic attack within six months
Any prior history of hypertensive crisis or hypertensive encephalopathy
Clinically significant peripheral vascular disease or vascular disease (including aortic aneurysm or aortic dissection)
Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies
Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of either serous or endometrioid cancer based on local histopathological findings; both endometrioid and serous histology should be high-grade for eligibility of non-mutation carriers; patients with clear cell, mixed epithelial, undifferentiated carcinoma, or transitional cell carcinoma histologies are also eligible, provided that the patient has a known deleterious germline BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory* Note: Due to the long acceptance of BRCA testing through Myriad, Myriad testing will be accepted; if testing for BRCA is done by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) listing the mutation and confirming that the laboratory results showed a recognized germ line deleterious BRCA 1 or BRCA 2 mutation or BRCA rearrangement is required; a copy of Myriad or other BRCA mutational analysis (positive or variants of unknown significance [VUS] or negative) reports will be requested but not required for study enrollment
Patients should have recurrent platinum-resistant or- refractory disease - defined as disease that has progressed by imaging while receiving platinum or had recurrence within 6 months of the last receipt of platinum-based chemotherapy; rising CA125 only is not considered as platinum-resistant or refractory disease
Patients may not have had a prior anti-angiogenic agent in the recurrent setting; prior use of bevacizumab in the upfront or upfront maintenance setting is allowed
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid-stimulating hormone (TSH) within normal limits
Prior treatment affecting the VEGF/VEGFR pathway or the angiopoietin pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, nintedanib, and trebananib; bevacizumab used in the upfront setting in conjunction with chemotherapy and/or as maintenance to treat newly diagnosed disease will be allowed
History of stroke or transient ischemic attack within six months
Clinical significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)
Evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted
Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies
Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma, high grade B-cell lymphoma not otherwise specified, or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
Determination of activated B-cell�like (ABC) subtype by pre-registration central review
Diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
Forced expiratory volume in 1 second (FEV1) >= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
Forced vital capacity (FVC) >= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
No more than 3 prior regimens for large cell component (e.g. one induction and two salvage therapies); monoclonal antibody alone or involved field/involved site radiotherapy do not count as lines of therapy
Prior use of ibrutinib is allowed unless patient has had disease progression while receiving ibrutinib
Patient must have chemosensitive disease as defined by at least a partial response to salvage therapy at their latest assessment
Willingness to provide blood and urine samples for research purposes
Malabsorption syndrome or other conditions that would interfere with intestinal absorption
Patients who cannot tolerate pneumocystis jirovecii pneumonia (PJP) prophylaxis (i.e., known Bactrim and pentamidine allergies)
Adequate pulmonary function as assessed by oxygen saturation >= 90% when ambulating and not requiring supplemental oxygen
Patients requiring concurrent administration of valproic acid are also excluded
Patients who are chronically receiving aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs are not eligible
Patients who are currently receiving therapeutic anti-coagulation with heparin, low-molecular weight heparin or Coumadin are not eligible for this trial
Patients who are currently receiving belimumab (a monoclonal antibody for systemic lupus erythematosus) are not eligible
Patients who are currently receiving bisphosphonate derivatives are not eligible
Bleeding and thrombosis:* Patients with evidence of active bleeding: intratumoral hemorrhage by current imaging, or bleeding diathesis are not eligible* Patients with known or prior history in prior 3 months of esophageal varices are not eligible* Patients with a history of CNS arterial/venous thromboembolic events including transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to study enrollment are not eligible* Patients with a history of deep vein thrombosis (including pulmonary embolism) within 3 months prior to study enrollment are not eligible* Patients with a history of hemoptysis or other signs of pulmonary hemorrhage within 3 months prior to study enrollment are not eligible* Patients with a history of >= grade 3 bleeding disorders, vasculitis, or had a significant (>= grade 3) episode from the gastrointestinal bleeding, within 6 months prior to enrollment are not eligible* For part B: patients with CNS tumors and evidence of new CNS hemorrhage of more than punctate size and/or more than three foci of punctate hemorrhage on baseline magnetic resonance imaging (MRI) obtained within 14 days prior to study enrollment are not eligible; Note: echocardiogram (ECHO) gradient MRI sequences per institutional guidelines are required for patients with CNS tumors
Patients with a history of hypertensive crisis or hypertensive encephalopathy within 6 months of study enrollment are not eligible
Patient does not have known glucose?6?phosphate dehydrogenase (G6PD) deficiency (G6PD testing optional)
Patient is not actively breastfeeding (or has agreed to discontinue breastfeeding before the initiation of protocol therapy)
Patients who have had a hysterectomy or are planning to have an adjuvant hysterectomy following radiation as part of their cervical cancer treatment are ineligible
Patients with self-reported or known diagnosis of G6PD deficiency
Primary and/or metastatic breast tumor must be negative for over-expression of estrogen and progesterone receptors; patients with weak estrogen receptor and/or progesterone receptor expression (< 10% on immunohistochemistry [IHC]) will be eligible
Primary and/or metastatic breast tumor must be negative for human epidermal growth factor receptor (HER-2/neu) over-expression based on IHC (0 or 1+, 2+ if fluorescence in-situ hybridization [FISH] test is negative) or FISH (HER2/copy number of centromere of chromosome 17 [CEP17] ratio < 2.0 or < 4 Her-2/neu signals per nucleus)
Prior taxane is allowed (as long as the patient is not experiencing grade > 1 neuropathy and had no history of disease progression on a taxane therapy within 3 months prior to study enrollment)
Any other medical or psychiatric condition that in the opinion of the investigator would make the study therapy unsafe for the patient
World Health Organization (WHO)-defined acute lymphoblastic leukemia and either:* Relapsed after achieving remission* Refractory to therapy* Newly diagnosed and ineligible for intensive chemotherapy inductionNote: patients with T lineage and B lineage ALL are eligible for this trial; likewise, patients with Philadelphia chromosome positive (Ph+) (as long as they are not candidate for other therapies for Ph+) and Ph- ALL are eligible
At least 4 weeks away from any previous antineoplastic or investigational agent; patients may receive hydroxyurea or glucocorticoids for suppression of leukocytosis, but these must be stopped at least 24 hours (h) prior to initiation of therapy
Relapse after SCT is allowed but no active graft-versus-host disease (GVHD) as per treating physician; also must not exceed the number of prior induction regimens listed above; SCT does not count as line of therapy
Patients with diabetes controlled by diet or medication are allowed on trial; controlled diabetes is defined as FBG < 130 mg/kL in the context of this study
There are no prohibitions of specific medications on the basis of anticipated drug-drug interactions
Any patient receiving chronic corticosteroid administration prior to study enrollment is ineligible
Patients must have histologic diagnosis of osteosarcoma at original diagnosis
Patients must have had at least one episode of disease recurrence in the lungs without limitation on number of episodes of recurrence as long as they meet the following criteria:* Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission within 4 weeks prior to study enrollment*** Pathologic confirmation of metastases from at least one of the resected sites** For patients with bilateral pulmonary metastases, resection must be performed from both lungs and the study enrollment must be within 4 weeks from date of the last lung surgery* Note: If surgery related changes such as atelectasis are seen on the post-operative computed tomography (CT) scan, patients will remain eligible to enroll as long as the operating surgeon believes that all sites of metastases were resected; patients with positive microscopic margins will be eligible to enroll
Patients with distant bone metastases at original diagnosis or relapse (patients with only skip lesions will be eligible)
Patients with concurrent local and pulmonary recurrence at the time of enrollment; note: patients who had local recurrence previously that has been treated and now present with an isolated pulmonary recurrence and meet the surgical resection criteria stated above will be eligible
Patients with primary refractory disease with progression of the primary tumor on initial therapy
Patients with CNS disease or other sites of extra-pulmonary metastases at the time of most recent episode of disease recurrence preceding enrollment
Patients with a prior hypersensitivity reaction to sargramostim
Any number of prior therapies is allowed
Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiography (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; elevated thyroid stimulating hormone (TSH) with normal T3 and T4 are allowed; patients on thyroid replacement therapy are allowed
Current use of natural herbal products or other complementary alternative medications (CAM) or �folk remedies�
History of stroke or transient ischemic attack within 6 months prior to registration
NYHA classification of III or IV
Current cardiac arrhythmia requiring concurrent use of anti-arrhythmic drugs
History of hypertensive crisis or hypertensive encephalopathy within 3 years prior to registration
Clinically significant peripheral vascular disease or abdominal aortic aneurysm (> 5 cm) or aortic dissection; if known history of abdominal aortic aneurysm with >= 4 cm in diameter, all of the following must be met: * An ultrasound (US) within the last 6 months prior to registration will be required to document that it is =< 5 cm* Patient must be asymptomatic from the aneurysm* Blood pressure must be well controlled as defined in this protocol
History of hemoptysis or any significant bleeding within the last 1 month prior to enrollment
Presence of cavitation of central pulmonary lesion
Patients may not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted; the clinical indication for therapeutic anticoagulation must be clearly documented prior to enrollment and must be discussed with the P.I.; patients who are on greater than or equal to 2 anti-thrombotic agents, including but not limited to anti-platelet agents (non-steroidal anti-inflammatory drugs [NSAIDs]/aspirin, clopidogrel), heparin, low molecular weight heparin (LMWH), warfarin, and a direct thrombin inhibitor, will be excluded
Any condition that, in the opinion of the treating investigator would interfere with evaluation of the investigational product or interpretation of subject safety or study results
Patients with pre-existing retinal disease on ophthalmologic exam will be excluded
Any number of prior therapies are allowed
Women of non-child bearing potential must be:* Women more than 50 years must be post-menopausal for at least 12 months following the end of all exogenous hormonal treatments OR* Women under 50 years must be postmenopausal for at least 12 months following the end of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution OR* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Consumption of grapefruit or grapefruit juice is not permitted during the study; patients should not consume food or beverages containing the fruit or juice of grapefruits or Seville oranges within 7 days before the first dose of study drug and throughout the study
Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-V criteria for insomnia and score >= 10 on the Insomnia Severity Index
Be able to read and understand English
Have contraindications to functional testing or yoga participation according to the treating physician or the physician's designee
Have practiced yoga >= 1 day a week within the 3 months prior to enrolling in the study
Be planning to start yoga on their own during the time they are enrolled in the study
Have a confirmed diagnosis of sleep apnea or restless leg syndrome
Patient wishes to become pregnant* Note: patients who have undergone oocyte/embryo/ovarian tissue cryopreservation at breast cancer diagnosis and/or have a previous history of assisted reproductive technology (ART) are eligible
Patient must be premenopausal at breast cancer diagnosis, as determined locally and documented in patient record; (Note: it is understood that patients� menopausal status may be unclear at the time of study enrollment)
Patient must be without clinical evidence of loco-regional and distant disease, as evaluated according to institutional assessment standards and documented in the patient record
The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines
Patient must be accessible for follow-up
Post-menopausal patients at breast cancer (BC) diagnosis, as determined locally
History of hysterectomy, bilateral oophorectomy or ovarian irradiation
Patients with a history of prior (ipsilateral [ipsi]- and/or contralateral) invasive BC
Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient�s safety
Patients with a history of noncompliance to medical treatments and/or considered potentially unreliable
Patients with psychiatric, addictive, or any disorder that would prevent compliance with protocol requirements
Patients must have resectable primary tumor based on contrast-enhanced CT or MRI (CT or MRI without contrast as part of positron emission tomography [PET]/CT or PET/MRI is NOT acceptable; CT or MRI with contrast as part of PET/CT or PET/MRI is acceptable) of the chest, abdomen, and pelvis; the local interpreting radiologist must review the scans and sign the S1505 local radiology checklist prior to registration; resectable is defined as:* No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (and, if present, replaced right hepatic artery)* No involvement, or < 180 degrees interface between tumor and vessel wall, of the portal vein and/or superior mesenteric vein; and patent portal vein/splenic vein confluence* No evidence of metastatic disease; lymphadenopathy (defined as nodes measuring > 1 cm in short axis) outside the surgical basin (i.e., para-aortic, peri-caval, celiac axis, or distant nodes) is considered M1 disease and makes the patient ineligible; if, however, such nodes are biopsied and are negative, then enrollment can be considered after review with the study chairs* Note: for tumors of the body and tail of the pancreas, involvement of the splenic artery and vein of any degree is considered resectable disease
CT scans or MRIs used to assess disease at baseline must be submitted for central review
Patients must have surgical consult to verify patient is a surgical candidate within 21 days prior to registration
CA19-9 must be performed within 14 days prior to registration
Sites must seek additional patient consent for the future use of specimens
Any number of prior therapies are allowed
Patients receiving anticoagulation or anti-platelet therapy are excluded; excluded agents include heparin or low molecular weight heparin, warfarin, clopidogrel, ibuprofen and other nonsteroidal anti-inflammatory drug (NSAIDS), tirofiban, and other anticoagulants, drugs, or herbal supplements that affect platelet function; administration of heparin to keep subject's infusion lines patent is allowed; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are allowed; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention, may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor
Patients with an underlying condition predisposing them to bleeding or currently exhibiting signs of clinically significant bleeding
History of hypersensitivity to AZD9291 (or drugs with a similar chemical structure or class to AZD9291) or any excipients of these agents
Pathologic diagnosis of one of the following:* For dose escalation:** Confirmed diagnosis of peripheral T-cell lymphoma (PTCL) or angioimmunoblastic T-cell lymphoma (AITL) that is refractory to at least one line of therapy; anaplastic large cell lymphoma (ALCL) and natural killer T-cell lymphoma nasal type (NKTCL) are excluded** Advanced stage cutaneous T-cell lymphoma (CTCL), specifically CTCL NOS, small/medium T-cell lymphoma (SMTCL) and mycosis fungoides (MF) stage IB, IIA, IIB, III and IV that have relapsed after at least one specific prior therapy (e.g. interferon, photopheresis, denileukin difitox, bexarotene, etc); anaplastic cutaneous large cell lymphoma (ACLCL) and lymphomatoid papulopsis are excluded** Follicular lymphoma grade 1, 2 or 3A that meets the following criteria: *** Relapsed or refractory to at least 2 lines of therapy AND*** Relapsed or refractory post autologous cell transplantation (HCT)* For dose expansion/dose confirmation phase: ** Patients with confirmed diagnosis of peripheral T-cell lymphoma (PTCL) follicular type or angioimmunoblastic T-cell lymphoma (AITL) that is refractory to at least one line of therapy
Patients must have at least one measurable lesion that can be accurately measured with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, or physical exam (by calipers only); (PTCL, AITL and follicular lymphoma patients will be assessed on this study using the Lugano criteria for the evaluation of lymphomas; CTCL and MF patients will be assessed using International Society for Cutaneous Lymphomas [ISCL] and European Organization for Research and Treatment of Cancer [EORTC criteria])
Any history or evidence of opportunistic infection within 6 months of screening including tuberculosis, severe cytomegalovirus (CMV) or herpetic infections (such as disseminated herpes, herpes encephalitis, ophthalmic herpes)
History of primary immunodeficiency
All potential patients must undergo a tuberculosis (TB) test prior to study entry (either purified protein derivative [PPD] or QuantiFERON-TB Gold, whichever is preferred and available at the Institution); patients with a history of TB (even if treated), or evidence of active or latent TB, are excluded; the diagnosis of active TB is defined per current guidelines; patients with a positive TB test (e.g. PPD or QuantiFERON-TB Gold) will be excluded; patients with history of Bacille-Calmette-Guerin (BCG) vaccination will be tested with QuantiFERON-TB Gold test in order to rule out exposure to TB
Patients with a weight of < 39 kg
Patients at institutions that elect to utilize central imaging review to confirm eligibility must be pre-registered prior to submission of these images; images should be submitted as soon as possible after the pre-registration magnetic resonance imaging (MRI) is obtained; turnaround time for this review will be =< 72 business hours after receipt of images by the Imaging and Radiation Oncology Core (IROC)
Patients at institutions that elect to confirm eligibility locally may be pre-registered at the same time as they are randomized
A diagnosis of radionecrosis will be based on a clinical onset of symptoms and radiological findings of radionecrosis at 3-24 months following radiosurgery, with or without pathological confirmation
Symptomatic brain radionecrosis to at least one lesion following radiosurgery treatment for brain metastases where symptomatic is defined as:* New or increasing headache associated with mass effect, sensory or motor abnormality, cognitive changes, speech difficulty, balance or coordination difficulty, cranial nerve deficits* Symptoms are persistent or worsening despite administration of at least dexamethasone 4 mg daily for 1 week
Clinical eligibility supported by central imaging real-time review* The presence of at least the following conventional magnetic resonance (MR) image characteristic:** Conventional MR*** Lesion quotient of < 0.3, where lesion quotient is defined as the proportional value of the maximum axial cross-sectional area of the transverse relaxation time (T2)-weighted defined lesion over the maximum axial cross-sectional area of the contrast-enhancing lesion on the longitudinal relaxation time (T1)-weighted post-gadolinium sequence on a comparable axial slice
If the conventional MR findings are not seen, the following dynamic susceptibility-contrast (DSC) MR characteristics may be used to meet eligibility for this study:* DSC MR** The cut-offs below will be based on gradient echo type echo planar imaging (GRE- EPI) DSC perfusion images, acquired without using a gadolinium pre-load:*** Relative cerebral blood volume (rCBV) < 1.5 in the enhancing-lesion relative to normal-appearing white matter (NAWM)*** Percentage of signal recovery (PSR) >= 76%, where PSR is determined by comparing the lower signal intensity during passage of the contrast bolus with the post-contrast signal intensity on the signal intensity-time curve
Centers that standardly use positron emission tomography (PET) or magnetic resonance spectroscopy (MRS) to determine a diagnosis of radionecrosis are permitted to use these modalities to assist in their patient selection; however the criteria described for conventional MR and/or DSC should also be met for study eligibility; both PET and MRS are not mandatory for study eligibility
No bevacizumab =< 3 months of study registration
Central imaging real-time review (72 hour turn around) to confirm eligibility (for institutions that opt to utilize central imaging review to confirm eligibility)
Able to participate in patient-report outcomes (MDASI-BT, DSQ-C, LASA) questionnaires; assistance by research personnel is acceptable if participant has disabilities that make reading or writing difficult
No evidence of recent hemorrhage at pre-registration MRI of the brain, however the following are permitted: presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor
Patients who have had a deep vein thrombosis or pulmonary embolus within the past 6 months are eligible if they are on stable therapeutic anticoagulation
No central lung metastases with excessive active bleeding
Undetectable haptoglobin or evidence of glucose-6-phophate dehydrogenase (G6PD) deficiency, pyruvate kinase deficiency, hemoglobinopathy, hereditary spherocytosis, thalassemia or other disorder associated with hemolysis
FOR PHASE I: If patient is on erlotinib at the time of signed consent, the patient does NOT need to be discontinued prior to initiation of erlotinib and onalespib; other EGFR-TKIs must be discontinued at least 7 days prior to initiation of erlotinib and onalespib
FOR PHASE II COHORT A: If patient is on erlotinib at the time of signed consent, erlotinib does NOT need to be discontinued prior to receiving treatment erlotinib and onalespib; last dose of erlotinib must be less than 28 days from when patient signs consent
History of pneumonitis attributed to an EGFR inhibitor; history of radiation pneumonitis is allowed provided steroid administration for pneumonitis was not required
Drugs that are known to increase torsades de pointes should be avoided; patients must discontinue these medications prior to enrollment on study; selection of alternate concomitant medications with no or minimal torsades de pointes potential is recommended
Treatment with proton pump inhibitors within 3 days prior to study entry; if treatment with an histamine (H2)-receptor antagonist such as ranitidine is required, erlotinib must be taken 10 hours after the H2-receptor antagonist dosing and at least 2 hours before the next dose of the H2-receptor antagonist; although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the erlotinib dose should be separated by several hours, if an antacid is necessary
Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren�s syndrome), congenital abnormality (e.g., Fuch�s dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration;* High-grade neuroendocrine carcinoma or combined SCLC and non-small cell lung cancer (NSCLC) is permitted
Patients must have a gadolinium contrast-enhanced three-dimensional (3D), spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) magnetic resonance imaging (MRI) scan and an axial T2/fluid attenuation inversion recovery (FLAIR) sequence; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; sites may contact the Imaging Co-Chairs for further information or assistance if needed* This MRI must be obtained within 56 days of Step 1 registration.* Note: the MRI study is mandatory irrespective of randomization to the experimental or control arm of this study
Note: the MRI study is mandatory irrespective of randomization to the experimental or control arm of this study
Patients who are primary English or French speakers are eligible
The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (parts A and B), and COWA; the neurocognitive assessments will be uploaded into the National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, and Gynecologic Oncology Group (NRG) Oncology RAVE system for evaluation by Dr. Wefel; once the upload is complete, within 3 business days, a notification will be sent to the site to proceed to Step 2 registration; at minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible
Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall. as determined by central assessment by the Neurocognitive Co-Chair, Dr. Wefel
Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt
Contraindication to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia
Patients must have had at least two prior chemotherapeutic or biologic (e.g. rituximab alone) regimens and not currently eligible for standard curative options; steroids alone and local radiation do not count as regimens
Concurrent use of other anti-cancer agents or treatments
At least 12 months have elapsed since platinum-based peri-operative treatment
Clinical staged III or IV HNSCC that is not amenable to surgical resection
Patients with primary oropharynx HNSCC must be HPV (-) according to local institutional definition using either p16 immunohistochemistry or HPV testing
Carcinoma of the neck of unknown primary site origin (regardless of HPV/p16 status) is eligible
Patients who are receiving adjuvant chemoradiation after surgical resection of the primary site of disease
Patients on tacrolimus or any other immunosuppressants with significant interaction with cisplatin
Definitive clinical or radiographic evidence of distant metastasis or adenopathy below the clavicles
Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study based upon stage, group, and age, as below
Patients with uncontrolled hyperglycemia
Patients with uncontrolled hyperlipidemia
Patients must have histologically confirmed, relapsed/refractory ALK+ ALCL (with ALK positivity defined by immunohistochemistry and/or fluorescence in situ hybridization [FISH]/cytogenetics from any prior biopsy), MCL, or BCL6+ DLBCL (with BCL6 positivity defined by immunohistochemistry from any prior biopsy) and meet the following criteria:
Potassium above the institutional lower limit of normal (supplementation to meet this is allowed)
Magnesium above the institutional lower limit of normal (supplementation to meet this is allowed)
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements* There will be no exclusion of patients with known visual impairment or symptoms, including by not limited to peripheral flashes (photopsia), blurred or double vision, floaters, color distortion and dimness, difficulties with light/dark accommodation, tunnel vision or other field defects, halos, apparent movement of stationary objects, and complex disturbances; patients will have a baseline ophthalmologic exam to serve as a point of comparison and further exams as needed should visual symptoms develop; no pretreatment eye exam findings or ocular symptoms have been associated with an increased risk of ocular toxicity seen with AT13387
History of noncompliance to medical regimens
AR expression detected by immunohistochemistry by central review
Patients must not have had any clinically-significant GI bleeding within 6 months prior to registration and patients must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula; examples of this include (but are not limited to) Crohn�s disease or tumor with transmural extension through the gastrointestinal lining
Patients must not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior to registration
Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies
Documented disease refractory to at least one PD1/PD-L1 inhibitor, defined as disease progression following at least 2 infusions of the same drug; radiographic disease progression will be documented by the institutional radiologist based on any radiographic evidence (magnetic resonance imaging [MRI], computed tomography [CT], positron emission tomography [PET], or other modalities, etc.) of disease progression on two separate radiographic scans assessment obtained at least 4 weeks apart; this minimum 4-week interval is required to define PD-1 inhibitor resistance based on imaging; alternatively, clinical disease progression may be documented on examination by the treating investigator
Patients with melanoma of mucosal or ocular primary
Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
Presence of transfusion-dependent thrombocytopenia
Prior exposure to ibrutinib or other ITK inhibitors
History of stroke or intracranial hemorrhage within 6 months prior to enrollment
Current life-threatening illness, medical condition, or organ system dysfunction, which, in the investigator�s opinion, could compromise the patient�s safety, or put the study at risk
Received anticoagulation therapy with warfarin, or equivalent vitamin K antagonists, within the last 28 days prior to day 1 of ibrutinib; patients with familial coagulopathic diseases (e.g. hemophilia, von Willebrand disease) are also excluded; if applicable, subjects must discontinue fish oil and vitamin E supplements within 7 days prior to initiating ibrutinib therapy
Subjects with known hepatic insufficiency (i.e. Child-Pugh score A [mild], Child-Pugh score B [moderate] or Child-Pugh score C [severe]) according to Child-Pugh criteria
Inclusion criteria associated with type and status of lymphoma
Biopsy-proven intermediate or high-grade non-Hodgkin�s lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment):* In partial remission* Relapsed after initial complete remission* Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease)* In complete remission with high-risk features as specified by the International Prognostic Index
Biopsy-proven advanced stage mantle cell lymphoma with proliferation-related Ki-67 antigen (Ki-67) > 10% in first complete remission (timeline 8 months prior to enrollment)
Biopsy-proven Hodgkin�s lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment)* In first, or greater relapse after initial complete remission* In partial remission* Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease)
Biopsy-proven Burkitt�s lymphoma, meeting one of the following criteria (timeline 8 months prior to enrollment):* In second complete remission after relapse following initial complete remission* Failed induction therapy, but responds (very good partial remission, complete remission, or near complete remission) to salvage therapy (i.e., chemosensitive disease)
Biopsy proven plasmablastic lymphomas, or peripheral T cell lymphoma (with the exception of anaplastic lymphoma kinase positive [ALK+] type in first or second complete remission) (timeline 8 months prior to enrollment)
NOTE: Patients meeting the following criteria are exempt from the 8 month timeline and do not require additional biopsy:* Patients who have never achieved a complete remission on the last biopsy-proven site of disease and went on to the next therapy then achieved a complete remission* Patients who relapsed quickly (within 3 months of their last chemotherapy) and now have achieved a complete remission with salvage therapy
INCLUSION CRITERIA ASSOCIATED WITH HIV-1 STATUS
Must be on a multi-drug anti-HIV regimen (excluding zidovudine [AZT, ZDV, Retrovir], or agents containing zidovudine [e.g., Combivir and Trizivir], and efavirenz [Sustiva], or agents containing efavirenz [e.g., Atripla]), and have an HIV-1 viral load < 50 copies/mL by reverse transcriptase-polymerase chain reaction (RT-PCR) within 6 months prior to study enrollment; for patients who have had negative viral loads in the past 6 months and no known HIV viral load (VL) > 500 copies/mL within the past 6 months, minor fluctuations of viral load (isolated escalations up to 500 copies/mL) are acceptable; the participant's history of negative viral loads may be documented with recent laboratory results and/or a record from the participant's HIV care provider; participants on zidovudine [AZT, ZDV, Retrovir; including Combivir and Trizivir] and efavirenz [Sustiva; including Atripla] must switch to an alternative regimen without anticipated drug-drug interactions or myelosuppressive properties based on known viral resistance patterns and/or ART history, such as raltegravir and Truvada (emtricitabine and tenofovir) at least two weeks prior to the transplant
Participants with CD4 counts > 50/microL are eligible for this study if their viral load is < 50 copies/mL by reverse transcription polymerase chain reaction (RT-PCR) since majority of the participants have received aggressive chemotherapy that can potentially decrease the CD4 counts despite the ART therapy; timeline: within 3 weeks prior to start of trial
GENERAL INCLUSION CRITERIA (TIMELINE: 8 WEEKS PRIOR TO START OF TRIAL, UNLESS OTHERWISE SPECIFIED)
Participants with hepatitis B should be on appropriate anti-viral therapy at the time of the transplant, and their viral load should be negative; timeline: within 3 weeks prior to enrollment
Forced expiratory volume in 1 second (FEV-1) or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) >= 50% predicted; timeline: within 4 weeks prior to enrollment
Receipt of a stable ART regimen for at least 3 weeks prior to start of trial
Participants with unexplained anemia, and/or thrombocytopenia
Participants with clear evidence of myeloproliferative disorders, or myelodysplastic disorders in the marrow
Any history of HIV-1 associated encephalopathy
Participants with persistently low CD4 counts less than 200 and a history of any acquired immune deficiency syndrome (AIDS)-defining infection in the last 6 months before screening are excluded from the study
Active cytomegalovirus (CMV) retinitis, or other active CMV-related organ dysfunction
Relapse of pneumocystis carinii pneumonia within the past year before enrollment
Intractable, severe diarrhea, defined as > 1.500 cc diarrheal fluid per day, or diarrhea causing persistent severe electrolyte abnormalities, or hypoalbuminemia
Dementia of any kind
Seizures within the past 12 months before enrollment
Active psychosocial condition that would hinder study compliance and follow-up
Any medical or physical contraindication, or other inability to undergo hematopoietic progenitor cell (HPC) collection
Life expectance of greater than two months to allow completion of study treatment and assessment of dose-limiting toxicity
Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, with stable systemic disease and ECOG score of 0-2, who would otherwise be eligible for SRS/stereotactic radiation therapy (SRT) alone should not be enrolled into this study unless WBRT is recommended due to any medical reasons or logistic limitations as determined by the treating physician; patients who develop recurrence post-SRS/SRT or surgery alone and are recommended WBRT will be eligible for the protocol
Presence of diffuse leptomeningeal carcinomatosis (focal/localized involvement is acceptable), > 1 cm mid-line shift, uncal herniation or significant hemorrhage/hydrocephalous (small intra-lesional hemorrhage is acceptable); patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
Patients must not have received prior WBRT (previous SRS/SRT done at least 4 weeks from the planned start of WBRT is acceptable); patients planned upfront to undergo SRS/SRT/fractionated boosts or neurosurgery after WBRT are not eligible; however, these treatments/procedures can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Patients needing more than 8 mg dexamethasone per day at the time of start of WBRT will not be eligible to participate in the study; however, patients will be allowed entry into the study if it is medically safe to reduce the daily dose of dexamethasone to 8 mg or less from the day of the start of WBRT; the dexamethasone dose for such patients may be increased beyond 8 mg per day during the course of treatment if medically necessary; this increased need for dose should be communicated to the study�s principal investigator, Dr Mohindra at the University of Maryland
Patients with known diagnoses that are associated with germline DDR defects such as Li Fraumeni syndrome and ataxia telangiectasia are excluded from the study
Classical Hodgkin lymphoma* Relapsed or refractory de novo classical Hodgkin lymphoma having failed standard first-line therapy; and* May have failed to achieve a response or progressed after treatment with brentuximab vedotin or may be brentuximab vedotin na�ve but is ineligible or unable to receive brentuximab vedotin; and* May have failed to achieve a response to, progressed after, or is ineligible for autologous stem cell transplant (auto-SCT)
Hepatocellular carcinoma (HCC)* Not eligible for curative attempt resection or liver transplant
Kaposi sarcoma (KS) (following prior KS-specific therapy (Cohorts 1-3)* (KS) impacting physical and/or psychological wellbeing and not amenable to local therapy and one or more of the following: ** Stable KS despite 6 or more cycles of liposomal doxorubicin or paclitaxel or other active cytotoxic agents (i.e. etoposide, bleomycin, anthracyclines, vincristine [vincristine sulfate], vinblastine); or** Progressive disease despite 3 or more cycles of liposomal doxorubicin or paclitaxel or other active cytotoxic agents (i.e. etoposide, bleomycin, anthracyclines, vincristine, vinblastine); or** Patient who received a cumulative lifetime dose of anthracycline of >= 550 mg/m^2; or** Recurrent or progressive KS after completion of prior first line chemotherapy** Intolerant of or refuses further cytotoxic chemotherapy** No KSHV-associated multicentric Castleman disease in past 5 years** For KS patients, the following laboratory values supersede values below:*** Platelets > lower limit of normal*** Hemoglobin > 10 g/dL
Treatment naive Kaposi sarcoma impacting physical and/or psychological wellbeing and not amenable to local therapy. (Cohort 4)* On antiretroviral therapy (ART) with suppressed HIV viral load for > 3 months (Note: an extended washout period is needed to avoid treatment during the period of risk for the highly toxic and often fatal �Immune Reconstitution Inflammatory Syndrome (IRIS)�* No KSHV-associated multicentric Castleman disease in past 5 years* No prior systemic chemotherapy * No symptomatic pulmonary KS or chest X-rays positive for un-evaluated abnormalities * Disease evaluable by AIDS Clinical Trial Group (ACTG) KS response criteria* CD4+ T-cell count >= 100 cells/uL * For KS patients, the following laboratory values supersede values below:** Platelets > lower limit of normal** Hemoglobin > 10 g/dL
On an effective combination cART regimen, generally a 3-drug regimen based on Department of Health and Human Services (DHHS) treatment guidelines* Patients must be on cART >= 4 weeks; and* Evidence of viral suppression defined as HIV viral load < 200 copies/mL; and * No symptomatic AEs > grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) criteria probably or definitely attributed to cART; and* No laboratory AEs noted on protocol defined screening laboratories > grade 1 by CTCAE criteria probably or definitely attributed to cART, with exceptions noted below* Note: if cART is modified during the screening period, patients must be on an effective new regimen for >= 2 weeks and otherwise meet eligibility criteria* Most patients have viral loads that are suppressible to < 50 copies/mL, but about 25% of patients will occasionally have blips up to 400�500 copies/mL, which do not appear to correlate with lack of viral suppression in most studies; thus, an HIV viral load of =< 400 copies/mL for an occasional �blip� will be allowed, if there is documentation of an HIV viral load < 200 on the same regimen and no significant treatment interruption
Patients must have marrow function and organ function as defined below* Note: to remain on treatment, any abnormal lab values allowed by the PI must remain stable or improve during treatment; similar off treatment rules will be applied to all patients, except the following: the grade of any abnormal laboratory (lab) value allowed by the protocol principal investigator (P.I.) at enrollment will be considered the patient�s baseline for potentially resuming therapy after modification/holding of therapy when off treatment criteria are applied
Creatine kinase < 5 X institutional ULN
Cirrhosis with Child-Pugh score of B or C
Grade 3-4 ascites or pleural effusion* Note: The following will NOT be exclusionary: A participant who is clinically stable following treatment for ascites or pleural effusion (including therapeutic thoracentesis or paracentesis)
Patient must be able to tolerate imaging requirements of an 18-FDG-PET-CT scan
Resting oxygen saturation (O2 sat) must be >= 92%
Patients with hypermetabolic para-aortic disease identified on baseline 18-FDG-PET-CT
Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded; pre-registration testing for G6PD is at the investigator�s discretion and is not required for study enrollment
No known hypersensitivity or contraindication to the components of study treatment (M6620 [VX-970], gemcitabine)
For oropharynx primary tumors, the patient must have negative human papillomavirus (HPV) status of the tumor as determined by p16 protein expression using immunohistochemistry (IHC)
Patients with recurrent disease or multiple primaries are ineligible
Per the operative report, the gross total resection of the primary tumor with curative intent was completed within 8 weeks prior to randomization
The patient must have the following assessments done =< 8 weeks prior to randomization:* Examination by a head and neck surgeon* Chest x-ray (or chest computed tomography [CT] scan or CT/positron emission tomography [PET] of the chest or magnetic resonance imaging [MRI]) to rule out distant metastatic disease
Patient must not have an intercurrent illness likely to interfere with protocol therapy
Patients must have metastatic and/or recurrent (distant or locoregionally recurrent) breast cancer and be HER2 non-over expressing per 2013 American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) HER testing guidelines (0 or 1+ by immunohistochemistry [IHC]; and/or HER2 ratio < 2.0 and HER2 copy number < 4 signals/cell by in-situ hybridization [ISH])* Local Regional Recurrence** In the breast (after preserving therapy)** In the chest wall (after mastectomy)** In the ipsilateral/parasternal/infra-or supraclavicular lymph nodes** In the skin of the chest wall (not breast)** In the reconstructed breast
Patients must also meet at least one of the following criteria:* Triple negative: histologically confirmed primary and/or metastatic site that is estrogen receptor (ER)-negative (=< 1%), progesterone receptor (PR)-negative (=< 1%), and HER2�negative* BRCA mutation: previously confirmed deleterious breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) germline mutation or suspected deleterious BRCA1 or BRCA2 germline mutation if the classification being used is the 5-tier classification; documentation of germline test results are required
Patients may receive bisphosphonates or denosumab concurrently with study treatment; if started prior to registration, it must be started at least 7 days prior to registration
Patients must have serum chemistries (including potassium and magnesium) within 21 days prior to registration to obtain baseline values
The preoperative Memorial Sloan-Kettering (MSK) nomogram estimates the patient�s likelihood of freedom from metastatic recurrence within the first 12 years following radical or partial nephrectomy to be =< 80%
Scheduled to undergo nephrectomy as part of treatment plan, per assessment through an MSK urologic surgeon listed as investigator on this trial
Availability of a frozen biopsy core prior to cycle 1, day 1
Absolute neutrophil count >= 1,500/mcL (without granulocyte colony-stimulating factor support within 2 weeks prior to cycle 1, day 1)
FOR PATIENTS ENROLLED IN THE EXPANSION COHORT: willingness to undergo mandatory biopsies (day -14, approximately 4 hours post end of irinotecan infusion and day 1, approximately 4 hours post end of irinotecan infusion [= 3 hours post end of VX-970]); patients enrolled to this cohort should have tumors deemed easily accessible for biopsies with low likelihood of complication
Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN protocol
Neutrophils >= 1000/uL
Patients must have had histologic verification of AML at original diagnosis
To be eligible for the phase 2 efficacy phase:* Relapse patients:** Patients must be in first marrow relapse, and ** Patients must not have received prior re-induction therapy; donor lymphocyte infusion (DLI) is considered a re-induction attempt
Intrathecal cytotoxic therapy:* No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone* At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection
Patients who have received > 450 mg/m^2 daunorubicin equivalents; patients who relapse after receiving AAML0531/AAML1031 therapy will be eligible for this study, provided they have not received any additional anthracyclines; NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:* Doxorubicin (doxorubicin hydrochloride): 1* Mitoxantrone: 3* Idarubicin: 3* Epirubicin: 0.5
Patients receiving medications for treatment of left ventricular systolic dysfunction
Patients with prior allergy to daunorubicin and/or cytarabine
Her-2 negative, defined as:* In-situ hybridization (ISH) ratio of < 2.0 (if performed)* Immunohistochemistry (IHC) staining of 0-2 positive (+) (if performed) * Deemed to not be a candidate for Her-2 directed therapy
Eligible tumor-node-metastasis (TNM) stages include:* Estrogen receptor (ER) and progesterone receptor (PR) negative (defined as < 1% staining for ER and PR by IHC): T2 or T3 N0, T0-3N1-3** Note: Patients with T1, N1mi disease are NOT eligible* ER and/or PR positive (defined as >= 1% staining for ER and/or PR on IHC): T0-3N1-3 or T3N0** Note: Patients with T0N0, T1N0 and T1, N1mi disease are NOT eligible* ER and/or PR positive (defined as >= 1% staining for ER and/or PR on IHC): T0-3N1-3 or T3N0** Note: Patients with T0N0, T1N0, T2N0 and T1-2, N1mi disease are NOT eligible* The eligibility of neo-adjuvant subjects can be assessed on the basis of clinical (c)TNM or pathologic (yp)TNM; the same eligible TNM combinations apply; patients may be eligible if they meet eligibility requirements at either time point, as long as they do not have T4 disease prior to therapy
Patients must have had a bilateral mammogram within 12 months prior to registration, unless the initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required; (subjects with bilateral total mastectomies do not require imaging)
Investigations, including chest X-ray or computed tomography (CT) chest, bone scan (with radiographs of suspicious areas) and abdominal ultrasound or liver scan or CT abdomen have been performed between the first histologic diagnosis and the time of registration* Chest X-ray, 2 view (or chest CT, or positron emission tomography [PET]/CT) is required only if clinically indicated or recommended by National Comprehensive Cancer Network (NCCN) guidelines* Bone scans (with x-rays of abnormal areas) are required only if indicated or recommended by NCCN guidelines* Abdominal imaging is required only if clinically indicated or recommended by NCCN guidelines
Surgical margins must be clear of invasive carcinoma; if there is microscopic residual ductal in situ disease present at lumpectomy or total mastectomy margins, further excision is highly recommended; if further excision is not undertaken, the subject may still be entered on study, provided that in addition to breast or chest wall irradiation, a boost to the tumor bed is delivered; in situ lobular disease at the margin is acceptable
All subjects (both adjuvant and neoadjuvant) must have sentinel lymph node biopsy and/or axillary lymph node dissection, as per pre-specified institutional guidelines
COMORBID CONDITIONS
No diabetes mellitus currently treated with insulin or sulfonylureas
No history of serious digestive and/or absorptive problems, including inflammatory bowel disease and chronic diarrhea that preclude adherence to the study diet
No history of severe cardiovascular, respiratory or musculoskeletal disease or joint problems that preclude moderate physical activity; examples would include unstable angina, recent myocardial infarction, oxygen-dependent pulmonary disease, and osteoarthritis requiring imminent joint replacement; moderate arthritis that does not preclude physical activity is not a reason for ineligibility
No history of psychiatric disorders that would preclude participation in the study intervention (e.g. untreated major depression or psychosis, substance abuse, severe personality disorder) or prevent the patient from giving informed consent
BMI >= 27 kg/m^2 documented within 56 days prior to study registration; the most recent body mass index (BMI) obtained must be used for eligibility; if most recent BMI is < 27 then the patient is not eligible to enroll
Self-reported ability to walk at least 2 blocks (at any pace)
Not participating in another weight loss, physical activity or dietary intervention clinical trial; co-enrollment in some trials involving pharmacologic therapy is allowed; participants in both arms are also allowed to pursue weight loss and physical activity programs on their own, as long as these programs are not provided as part of a clinical trial
Able to read and comprehend either English or Spanish
NON-PROGRESSED DIPG (STRATUM 2): BSA* Patients must have a BSA >= 0.80 m^2 for dose 5 mg/m^2* Patients must have a BSA >= 0.65 m^2 for doses of 10mg/m^2 - 22 mg/m^2* Patients must have a BSA >= 0.50 m^2 for doses of 28 mg/m^2 - 36 mg/m^2
Patients must have slides available for submission to central pathology review; this review is mandatory prior to registration to confirm eligibility and proper cohort assignment* HISTOLOGIC COHORT 1: Undifferentiated pleomorphic sarcoma (includes: malignant fibrous histiocytoma, myxofibrosarcoma, high grade sarcoma not otherwise specified [NOS])* HISTOLOGIC COHORT 2: Leiomyosarcoma (either uterine or extra-uterine)* HISTOLOGIC COHORT 3: Other (either malignant peripheral nerve sheath tumor or synovial sarcoma); during the phase II portion of the study, enrollment will be limited to maximum of 25 patients in this cohort** Note that the phase I is limited to the histologic subtypes listed above; since patients will be enrolling onto dose cohorts during the phase I, they will not enroll onto specific histologic cohorts, although the histologic subtype informed will be collected during patient enrollment
Histologic documentation: Eligible patients must have histopathologically confirmed sarcoma of one of the subtypes listed, by central review
Chronic concomitant treatment with proton pump inhibitors must discontinue the drug for 7 days prior to registration on the study
Thyroid stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH however if the Free T4 is normal and patient is clinically euthyroid, patient is eligible
Patients must be in their first platinum sensitive recurrence; this is defined as recurrence that occurred greater than six months after completion of first line platinum based therapy; for the phase 1 portion of the study, patients must have a platinum free interval between 6 months and 1 year and are not eligible or unwilling to undergo a second cytoreductive surgery
Children are excluded from this study, but will be eligible for future pediatric trials
Prior exposure to gemcitabine
Patients with Li Fraumeni syndrome are excluded from the study
IMAGING CORRELATIVE STUDY: Patients will be eligible to participate in the FMX imaging study if the participating study center offers this test and they do not meet any of the following criteria:* Evidence of iron overload as determined by:** Fasting transferrin saturation of > 45% and/or** Serum ferritin levels > 1000 ng/ml* A history of allergic reactions to any of the following:** Compounds similar to ferumoxytol or any of its components as described in full prescribing information for ferumoxytol injection** Any IV iron replacement product (e.g. parenteral iron, dextran, iron-dextran, or parenteral iron polysaccharide preparations)** Multiple drugs* Unable to undergo MRI or for whom MRI is otherwise contraindicated (e.g. presence of errant metal, cardiac pacemakers, pain pumps or other MRI incompatible devices; or history claustrophobia or anxiety related to undergoing MRI)
Patients who have severe hypersensitivity to irinotecan hydrochloride (HCl)
Patients at the National Cancer Institute (NCI) site and other selected centers who are willing to undergo an optional pre-treatment ferumoxytol MRI must not have evidence of iron overload, a known hypersensitivity to ferumoxytol or any other IV iron product, a documented history of multiple drug allergies, or those for whom MRI is otherwise contraindicated, including claustrophobia or anxiety related to undergoing MRI; this exclusion criterion applies only to patients enrolling at NCI and other selected sites; of note, the principal investigator (PI) will allow other centers to offer FMX MRI scans if the site in question is willing and the site PI can identify the necessary resources and expertise at their center
Documentation of HTLV infection (enzyme linked immunosorbent assay [ELISA]) in individual with confirmation of HTLV-1 infection (by immunoblot or polymerase chain reaction [PCR]) or a consistent clinical picture (including two of the following: 1) CD4+ leukemia or lymphoma, 2) hypercalcemia, and/or 3) Japanese, Caribbean or South American birthplace)
Current or prior HTLV-1 associated inflammatory diseases, including but not limited to myelopathy, uveitis, arthropathy, pneumonitis, or a Sjogren�s disease-like disorder
Patients must have CA19-9 obtained within 14 days prior to registration; if CA19-9 is normal a carcinoembryonic antigen (CEA) must be tested within 14 days prior to registration
Patients must not have known hypersensitivity to irinotecan, fluorouracil, or leucovorin
Patients must be offered the opportunity to participate in specimen banking for future use
CLINICAL/LABORATORY CRITERIA: Patients must have corrected QT (QTc) interval =< 480 msec (using the Bazett�s formula) on electrocardiogram (ECG) performed within 42 days prior to registration; history or evidence of current clinically significant uncontrolled arrhythmias are not eligible; however, patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible; patients must not have atrial fibrillation > grade 2 on the screening ECG; patients with CTCAE grade 1-2 atrial fibrillation on their screening ECG must have a second ECG performed prior to registration and more than 30 days from the screening ECG (either before or after) with the most recent ECG showing stable or improving grade of atrial fibrillation
SPECIMEN SUBMISSION CRITERIA: Patients must be offered optional participation in banking of specimens for future research
(STEP 1) - PRIMARY INTERVENTION STUDY (RANDOMIZED CONTROLLED TRIAL [RCT]):
Patients must be registered to the first screening step (Step 0) for the National Cancer Institute (NCI)-MATCH trial (EAY131)
Patients must speak English and have an adequate ability to view a website (primary intervention study)
(STEP 2) - SECONDARY GENETIC COUNSELING SUBSTUDY:
Patients must have a potential germline mutation, as determined by the NCI-MATCH tumor profiling assay
Patients must be able to speak English and hear by phone
Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
Patients must have been assigned to S1400I
Patients must not have any known allergy or reaction to any component of the nivolumab and ipilimumab formulations
Patients must also be offered participation in banking for future use of specimens
Patients must have a lipase, amylase, TSH with reflex free T3/T4 performed within 7 days prior to sub-study registration; (Note: For the Canadian sites, testing for lipase only is acceptable)
Patients who can complete PRO forms in English are required to complete a pre-study S1400I Patient Reported Outcomes (PRO) Questionnaire and a pre-study S1400I EQ-5D Questionnaire within 14 days prior to registration; NOTE: Patients enrolled to S1400I prior to 9/1/2016 are not eligible for the PRO study
Biopsy-proven KS involving skin (with or without visceral involvement) without need for urgent cytotoxic therapy; there should be no evidence of improvement in KS in the 4 weeks immediately prior to study enrollment
Participant may be either previously untreated for KS or refractory to or intolerant of any one or more prior KS therapies
HIV seropositive participants must be on antiretroviral therapy (ART) with the following criteria:* A complete ART regimen that does not include the study drug as one of a minimum of 3 active drugs, which may include an integrase inhibitor or efavirenz in combination with nucleoside reverse-transcriptase inhibitors (NRTIs)* The ART regimen must not include protease inhibitor (PIs); participants must not have received a PI-based regimen for at least 4 weeks prior to enrollment* Participants must either have an undetectable HIV plasma ribonucleic acid (RNA), or if plasma RNA detectable, must be on the same stable regimen for a minimum of 12 weeks prior to study enrollment* No minimum cluster of differentiation (CD)4 count, but maximum HIV plasma RNA of 1,000 copies/mL
Chronic diarrhea as defined by loose or watery stools occurring more than 3 times daily at baseline lasting more than 4 weeks or not abating on condition-appropriate therapy prior to study enrollment
Patients must be newly diagnosed and have a confirmed molecular diagnosis of classical histologic type (non large cell/anaplastic [LC/A]) WNT medulloblastoma from rapid central pathology screening review on APEC14B1 (immunohistochemistry [IHC]/molecular screening [positive nuclear beta (B)-catenin by IHC and positive for catenin beta 1 [CTNNB1] mutation) and confirmation of =< 1.5 cm^2 maximal cross-sectional area of residual tumor from rapid central imaging review
Patient must have negative lumbar cerebrospinal fluid (CSF) cytology; CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF; ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study* Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status
Patients must have eligibility confirmed by rapid central imaging review on APEC14B1; standard whole brain magnetic resonance imaging (MRI) with and without contrast (gadolinium) and spine MRI with contrast (gadolinium) must be performed at the following time points:* Pre-operative to include an MRI of the brain with and without contrast (including post-contrast three-dimensional [3D] T1-weighted image [T1WI] and post-contrast fluid-attenuated inversion recovery [FLAIR])* Pre-operative spinal MRI with gadolinium; post-operative staging spinal MRI may be obtained if pre-operative imaging is not possible or is suboptimal; pre-operative spine imaging is strongly preferred, due to the potential of post-operative sequelae, which could affect metastasis detection* Post-operative brain MRI within 72 hours of surgery
Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
Patients diagnosed with a leukemia or lymphoma as follows:* Chronic or acute leukemia forms of HTLV-1 associated adult T-cell leukemia;* Peripheral T-cell lymphoma (angioimmunoblastic, hepatosplenic, or not otherwise specified); or,* Cutaneous T-cell lymphoma stage III or IV with circulating monoclonal cells (B1 or B2) and/or erythrodermia (T4)* T-cell prolymphocytic leukemia (T-PLL)* NOTE: Diagnosis must be validated by the Pathology Department, National Cancer Institute (NCI)
Patients must have measurable or evaluable disease; NOTE: All patients with greater than 10% abnormal CD4+ homogeneous CD3^low strongly CD25+ expressing cells, or greater than 5% Sezary/T-PLL cells, among the peripheral blood mononuclear cells (PBMCs) in the peripheral blood will be deemed to have evaluable disease
Abnormal T cells must be CD52+ as assessed by flow cytometry or immunohistochemistry
Patients must have been refractory or relapsed following front line therapy for adult T-cell leukemia (ATL); those with cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL) who have CD30+ disease must have progressed during or after treatment with brentuximab vedotin, or are unable to receive treatment due to allergy or intolerance
Diffusing capacity divided by the alveolar volume (DDLCO/VA) and forced expiratory volume (FEV) � 1.0 > 50% of predicted on pulmonary function tests
All patients must use adequate contraception during participation in this trial and for 3 months following completing therapy
History of severe asthma or presently on chronic inhaled corticosteroid medications (patients with a history of mild asthma not requiring corticosteroid therapy are eligible)
Patients with smoldering and lymphomatous ATL
Patients with suspected non-gynecologic malignancy, such as gastrointestinal
Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including serous, clear cell or other FIGO grade 3 lesions
Patients with any condition that in the judgment of the investigator would jeopardize safety or patient compliance with the protocol
Patients who are unwilling to be transfused with blood components
Patients who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations
Diagnosis of adenocarcinoma of the rectum with the major portion of the tumor intact; Note: prior to randomization, the investigator must specify and document each of the following: * Distance of the lowest tumor margin from the anal verge; and * Intent for sphincter sparing or non-sphincter sparing surgical resection according to the primary surgeon; and* The majority of the untreated tumor must be < 12 cm from the anal verge or below the peritoneal reflection as determined by the treating surgeon
Serum potassium, magnesium, and calcium levels within 28 days before randomization must be within normal limits (WNL) for the lab within 28 days before randomization
Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 28 days prior to randomization; Note: Distant clinical staging to exclude patients with overt metastatic disease is determined by:* Chest: CT scan (preferred); chest x-ray posterioranterior (PA) and lateral (acceptable); or positron emission tomography (PET) scan (acceptable)* Abdomen: CT scan with IV contrast (preferred); or MRI (acceptable)* Pelvis: MRI (preferred) or CT scan with IV contrast (acceptable)** (It is recommended that the same imaging tests that are performed before randomization be used at follow-up time points; Note: CT scans of the abdomen and pelvis must be performed with IV contrast)
History of, or any evidence of active, non-infectious pneumonitis
Active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic) or have a history of abdominal surgery or other medical condition that may, in the opinion of the treating physician, interfere with gastrointestinal motility or absorption
History of active TB (Bacillus tuberculosis)
Synchronous colon cancer
Known homozygous DPD (dihydro pyrimidine dehydrogenase) deficiency
Co-morbid illnesses or other concurrent disease that, in the judgement of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens or prevent required follow-up
Males and females must weigh >= 40 Kg
Patient must have a lifetime cumulative anthracycline dose of >= 250 mg/m^2 DOXOrubicin equivalent without the protection of dexrazoxane (Zinecard) therapy; the anthracycline dose threshold must be met as part of the treatment of a cancer that was diagnosed at < 22 years of age* Note: Institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) can be used to document lifetime receipt of anthracycline dose
Uncorrected primary obstructive or severe regurgitative valvular disease:* Nondilated (restrictive); or* Hypertrophic cardiomyopathy; or* Significant systemic ventricular outflow obstruction
Sustained or symptomatic ventricular dysrhythmias uncontrolled with drug therapy or implantable device
Significant conduction defects (i.e. second or third degree atrio-ventricular block or sick sinus syndrome)
Bradycardia: heart rate < 50 beats per minute (BPM)
Use of an investigational drug or beta adrenergic blockers, including metoprolol, sotalol, within 30 days of enrollment
History of drug sensitivity or allergic reaction to alpha or beta-blockers
History or current clinical evidence of moderate-to-severe obstructive pulmonary disease or reactive airway diseases (i.e. asthma) requiring therapy
Gastrointestinal, or biliary disorders that could impair absorption, metabolism, or excretion of orally administered medications
Endocrine disorders (such as primary aldosteronism, pheochromocytoma, hyper- or hypothyroidism) not controlled with medication
Uncontrolled diabetes (controlled diabetes per the American Diabetes Association and International Diabetes Center�s Glycemic Target Goals is hemoglobin A1C < 7%)
Anemia (hematocrit < 28%)
Any ER/progesterone receptor (PgR) status allowed
Regular nonsteroidal anti-inflammatory drug (NSAID)/aspirin use at any dose (including baby aspirin) (defined as >= 5 days per week) is allowed if aspirin and/or NSAIDs are stopped for 30 days prior to study entry and throughout the study period; participants will be encouraged to use acetaminophen for minor pain and fever
Patients must be enrolled within 1 year after diagnosis
Patients with a prior history of gastric/duodenal ulcers documented on endoscopy can be enrolled as long as the ulcers did not cause bleeding requiring a blood transfusion/major intervention; for patients who are Helicobacter pylori positive, a course of Helicobacter pylori eradication treatment must have been completed
No history of gastrointestinal bleeding (GI) bleeding requiring a blood transfusion, endoscopic or operative intervention
No history of any prior stroke (hemorrhagic or ischemic)
No concurrent anticoagulation with warfarin or heparin/heparin analogues, clopidogrel, oral direct thrombin inhibitors, or direct factor XA inhibitors
No history of grade 4 hypertension, defined as hypertension resulting in life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis)
No known allergy to aspirin
Patents must be scheduled for routine screening DBT
Patient�s breast density must be known; patients must have mammographically dense breasts, American College of Radiology (ACR) Breast Imaging (BI)- Reporting and Data System Atlas (RADS) lexicon categories c or d (heterogeneous or extreme fibroglandular tissue) on their most-recent prior screening
Patient must be asymptomatic for breast disease and undergoing routine screening
Patient must not have undergone breast ultrasound within 12 months prior to randomization
Patient must not have previously had a breast MRI
Patient must not have previously had molecular breast imaging (MBI, multiplexed ion beam imaging [MIBI])
Patient must agree to not undergo screening ultrasound (of breast) for the duration of the 1 year study period
Patient must be able to undergo breast MRI with contrast enhancement; patients unable to undergo breast MRI with contrast enhancement for any reason are ineligible* No history of untreatable claustrophobia* No presence of non MR compatible metallic objects or metallic objects that, in the opinion of the radiologist, would make MRI a contraindication* No history of sickle cell disease* No contraindication to intravenous contrast administration* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance* No known or suspected renal impairment; requirements for glomerular filtration rate (GFR) prior to MRI as determined by local site standard practice* Weight less than or equal to the MRI table limit* No women who have had prior contrast enhanced mammography (contrast enhanced spectral mammography [CESM] or contrast enhanced digital mammography [CEDM])* No women who have breast prosthetic implants (silicone or saline)
Patients must not have any known contraindication to CSFs prior to registration, including prior hypersensitivity to Escherichia coli-derived proteins, filgrastim, pegfilgrastim, or tbo-filgrastim
Patients must be able to understand and provide information for the patient-completed study forms in either English or Spanish
Patients may have had a prior malignancy
Patients must not be participating or plan to participate in other clinical trials that involve investigational systemic cancer treatments or investigational uses of CSF during their first 6 months after registration
Patients must have at least one �target lesion� to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as �non-target� lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry
Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell
Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration
Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration
Concurrent diagnosis of pheochromocytoma
Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation
Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study
Anti-arrhythmic therapy other than beta blockers or digoxin
Preoperative biopsy for confirmation of renal cell carcinoma (RCC) must be performed within four (4) months prior to randomization* If biopsy was performed as part of patients standard care, and will not be performed during step 0 proceed directly to randomization
Patients with newly diagnosed higher risk RCC of any histology including sarcomatoid or (if preoperative biopsy was uninformative) - �unknown� histology; RCC must have been confirmed by biopsy within 4 months prior to randomization; if the biopsy clearly demonstrated a benign condition or a different type of cancer, the patient is not eligible to be randomized
Patients must have no clinical or radiological evidence of distant metastases (M0)
Patient must have no prior history of RCC that was resected with curative intent within the past 5 years
No uncontrolled adrenal insufficiency
No known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator�s opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results
Patients currently enrolled in other clinical trials testing a therapeutic intervention
Absolute granulocyte count (AGC) >= 1,500/mm^3, within 4 weeks of randomization
During the expansion phase of the protocol, patients must have disease amenable to biopsy and be willing to undergo pre- and post-treatment biopsies
Patients required to be on any of the concomitant medications are excluded
Patients in the expansion cohort undergoing tumor biopsies may not be on anticoagulants
Patients must have had all grossly visible papillary tumors removed within 30 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 30 days prior to registration
Patients must have high-grade bladder cancer as defined by 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification
Patients� disease must not have micropapillary components
Patients must have no evidence of upper tract (renal pelvis or ureters) cancer confirmed by one of the following tests performed within 90 days prior to registration: CT urogram, intravenous pyelogram, magnetic resonance (MR) urogram, or retrograde pyelograms
Patients must not be taking oral glucocorticoids at the time of registration
Patients must not have known history of tuberculosis
Patients must be PPD negative within 90 days prior to registration; PPD negativity is defined as < 10 mm diameter induration (palpable, raised hardened area) in the volar forearm at 48-72 hours following injection with standard tuberculin dose (5 units, 0.1 ml); for PPD readings done outside of 48-72 hour window, patients must have PPD test and reading repeated to confirm eligibility
Patients must be offered the opportunity to participate in specimen banking for future studies to include translational medicine studies
Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review
No definitive resection of pancreatic cancer
No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease) within 28 days of registration
For patients with CNS tumors, any baseline neurologic deficit, including seizures, must be stable for at least one week prior to initiating study treatment
Patients must have lactate dehydrogenase (LDH) performed within 28 days prior to registration
Patients must not have history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Patients must have specimens available and institutions must be planning to submit for centralized pathology review and for integrated translational medicine objectives
Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx squamous cell carcinoma (SCC) within 63 days prior to registration; note: patients may have a biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but demonstrate rapid gross recurrence or are determined to have gross persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
Patients must have at least one of the following high risk pathologic features:* Extracapsular nodal extension* Invasive cancer at the primary tumor resection margin (tumor on ink); Note: Patients who have a positive margin and undergo re-resection with final negative margin are eligible only if they can be enrolled within 63 days of initial gross total resection AND extracapsular nodal extension was also present; patients who have a positive margin and undergo re-resection with final negative margin and do not have extracapsular nodal extension, are NOT eligible
Pathologic stage III or IV HNSCC, including no distant metastases, based on the following minimum diagnostic workup:* General history/physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration* Examination by an ear nose and throat (ENT) or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation* Pre-op Imaging of the head and neck: a neck computerized tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via transfer of images and data (TRIAD); the report is to be uploaded into Rave* Chest imaging with either a CT scan (with or without contrast) or CT/PET (with or without contrast) that includes the chest within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
For patients with oropharyngeal cancer only: the institution will do p16 testing, and if p16 is negative, this tissue must be submitted for central review for confirmation before Step 2 registration; note: if the institution finds that the patient is p16 positive, the patient is excluded from this trial on the basis of distinct biology, prognosis, and low- or intermediate-risk rather than high-risk status
The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chlorine (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; note: patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator�s discretion
Patients with feeding tubes are eligible for the study
Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 differentiated thyroid carcinoma, who are eligible
Patients who are pregnant, nursing, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of MK-3475 (pembrolizumab)
Hypersensitivity to MK-3475 (pembrolizumab) or any of its excipients;
Patients for whom it is not in the best interest to participate in the study, in the opinion of the treating investigator
Patients requiring concurrent administration of valproic acid are not eligible for this trial
Patients with a BSA ? 1.17 m^2 at time of study enrollment are not eligible
Patients with a history of allergy to medications that have a benzamide structure (e.g., metoclopramide, procarbazine, domperidone, cisapride etc.) are not eligible
Anticoagulation with low-molecular-weight heparin (LMWH) will be permitted; patients receiving treatment with warfarin or any of the new oral anticoagulants (NOACs) (rivaroxaban, apixaban, dabigatran, or edoxaban) will be given the option to switch to LMWH
History of allergic reactions to SGI-110 or decitabine
Appropriate stage for study entry based on the following diagnostic workup:* History/physical examination by a radiation oncologist (and a surgeon if surgery is planned) within 30 days prior to registration* Imaging proof of limited metastatic disease and response to therapy/stable disease, by at least diagnostic quality computed tomography (CT) chest through the adrenals or positron emission tomography (PET)/CT, within 30 days prior to registration.
Subjects may receive palliative radiotherapy for symptomatic metastases prior to enrollment provided that there is at least one other non-irradiated lesion amenable to LCT at the time of enrollment.
Cutaneous metastasis of NSCLC.
Metastases located within 3 cm of previously irradiated (< 3Gy per fraction) structures if not a candidate for surgery for these lesions and if:* Spinal cord previously irradiated to > 40 Gy* Brachial plexus previously irradiated to > 50 Gy* Small intestine, large intestine, or stomach previously irradiated to > 45 Gy* Brainstem previously irradiated to > 50 Gy* Lung previously irradiated with prior V20 Gy > 35%
If a patient has progressed in previous areas of primary disease that received definitive doses of radiation, these patients would require re-irradiation in previous high dose anatomic areas and are not eligible for this study.
Participation in any investigational drug study (excluding non-oncology and/or symptom management studies) within 4 weeks prior to registration.
Patients must have failed standard therapy and at the time of study entry have recurrent, progressive or refractory disease with no known curative options
Patients must have had their last fraction of: * Craniospinal irradiation (> 24 Gy) > 3 months prior to enrollment* Focal irradiation > 42 days prior to enrollment* Local palliative irradiation (small port) > 14 days
Patients with neurological deficits should be stable for a minimum of 1 week prior to enrollment
Patients must have minimum head circumference of 44 cm
Patients must be willing to use the Optune device >= 18 hours/day for at least 23 days in a 28-day cycle, and keep head shaved throughout treatment
Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient�s first malignancy has been in remission for at least 5 years from the end of treatment
Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to device usage plan, other study procedures, and study restrictions
Patients with primarily infra-tentorial or spinal cord tumor are not eligible
Patients with major skull defects (such as missing bone without replacement) are not eligible
Patients with active implanted electronic devices in the brain or spinal cord such as programmable VP shunts, deep brain stimulators, vagus nerve stimulators, are not allowed
Patients with pacemaker, defibrillator, or documented significant arrhythmia, are not allowed
Patients with foreign body intracranially, such as bullet fragments, are not allowed, with the exception of VP-shunts (non-programmable) and Ommaya catheters
Patients with history of hypersensitivity to conductive hydrogel are not eligible
Patients must be able to undergo appropriate imaging studies to monitor tumor response
Cardiac Function: Fridericia's correction formula (QTcF) < 480 milliseconds (Fridericia correction), and ejection fraction (EF) >= 50%
Patients will be strongly encouraged to participate in 10-C-0086; if a patient does not agree to enroll on 10-C-0086, germline genetic analysis will not be performed
Patients who require concurrent treatment with antithrombotic and/or anti-platelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, and/or ibuprofen)
Patients may not have any clinically significant cardiovascular disease including the following:* Myocardial infarction or ventricular tachyarrhythmia within 6 months* Major conduction abnormality (unless a cardiac pacemaker is present)* Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out corrected QT (QTc) prolongation; the patient may be referred to a cardiologist at the discretion of the principal investigator; patients with underlying cardiopulmonary dysfunction should be excluded from the study
Patients with known pre-existing diabetes mellitus
Patients post-prostatectomy with baseline Gleason >= 7 (per prostatectomy pathology)
Baseline PSA nadir >= 0.2 ng/ml (post-operative value is never undetectable) obtained prior to step 1 registration
Baseline testosterone level obtained post prostatectomy prior to step 1 registration
Pathologically (histologically) proven diagnosis of adenocarcinoma of the prostate as confirmed at time of prostatectomy; prostatectomy must have been performed =< 365 days (1 year) prior to step 1 registration any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted; (please note: Prior ablative treatment for benign prostatic hypertrophy or focal high-intensity focused ultrasound therapy [HIFU] prior to prostatectomy is allowed)
Prior androgen deprivation (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior to study enrollment and given for =< 90 days duration* For example: Patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a 22.5 mg sustained release dose of leuprolide acetate is given (3 month duration), then the expected duration of such a dose would be 90 days after the injection date; for a 7.5 mg leuprolide (1 month duration), the discontinuation date would be 30 days after the injection date* Please note: Finasteride or dutasteride must be stopped before treatment but should not determine eligibility
Pathologically proven to be lymph node negative by pelvic lymphadenectomy (pN0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [pNx])
Any pT-stage based on American Joint Committee on Cancer 7th edition eligible; study entry will be based on the following diagnostic workup:* History/physical examination within 60 days prior to step 1 registration* Negative distant metastatic workup: ** A computed tomography (CT) scan of the abdomen and pelvis (with contrast [CT without contrast is permitted if the patient is not a candidate for contrast, i.e., renal function or allergy]) or magnetic resonance imaging (MRI) of the pelvis within 120 days prior to step 1 registration; (Please note: Lymph nodes will be considered negative (NO)if they are =< 1.5 cm short axis);** Bone scan within 120 days prior to step 1 registration; (please note: a sodium fluoride [NaF] positron emission tomography [PET]/CT is an acceptable substitute and if the bone scan is suspicious, a plain x-ray, CT scan, NaF PET/CT and/or MRI must be obtained to rule out metastasis)
Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound [HIFU]) for prostate cancer is allowed; prior focal HIFU or treatment for benign prostatic hypertrophy is allowed
Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia) or acute leukemia of ambiguous lineage (ALUL), which includes mixed phenotype acute leukemia (MPAL); for patients with ALUL, the morphology and immunophenotype must be at least 50% B lymphoblastic
Patients with known absence of KMT2A-rearrangement leukemia prior to enrollment
Willingness to provide biopsy samples for research purposes (patients >= 18 years of age at the National Cancer Institute [NCI] Clinical Center only)
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon-alpha or interleukin-2 [aldesleukin]) within 6 weeks prior to cycle 1, day 1.
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography  (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with active tuberculosis (TB) are excluded
Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
Patients are eligible under ONE of the following criteria:* Patients must have histologically confirmed rare cancer and must be able to submit specimens; NOTE: Subsequent to site�s Institutional Review Board (IRB) approval of revision 3, patients are NOT required to participate in EAY131 �National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)� to register to this study* FOR PATIENTS ENROLLED IN EAY131 �NCI-MATCH� PRIOR TO EAY131 ADDENDUM 10 ONLY: Patients must have histologically confirmed rare cancer that did not have a match to a molecularly-guided therapy on EAY131 �NCI-MATCH� protocol or who are off protocol treatment on EAY131, �NCI-MATCH� and have no further molecularly-matched treatment recommendations per EAY131, �NCI-MATCH� or who are otherwise unable to receive EAY131, �NCI-MATCH� therapy
Patients that do not qualify for one of the histologic cohorts may be considered for registration in the �Not Otherwise Categorized� Rare Tumors cohort with confirmation of at least one of the study chairs via email
Patients that are determined to have a rare cancer with unknown primary site are eligible under cohort #32 (tumor of unknown primary [cancer of unknown primary; CuP]), provided that there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated cross-sectional imaging of the chest, abdomen, and pelvis
Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible
Patients must not have prior history of allergy or known hypersensitivity to nivolumab or ipilimumab
Patients must have adequate thyroid function, as evidenced by either thyroid-stimulating hormone (TSH) or, free thyroxine (T4) serum tests demonstrating values within the normal range, within 28 days prior to registration; Note: TSH, with reflex T4 is allowable if per institutional standard; otherwise, both TSH and free-T4 must be obtained
Patients must have adequate adrenal axis function, as evidenced by adrenocorticotropic hormone (ACTH) values within the institutional normal ranges OR cortisol levels within institutional normal ranges (ante meridiem [AM] cortisol preferred), within 28 days prior to registration
Patients must have amylase or lipase within =< 1.5 x IULN without symptoms of pancreatitis at registration, within 28 days prior to registration
Thyroid-stimulating hormone (TSH) within normal limits (TSH < ULN allowed in euthyroid patients on thyroid replacement therapy)
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with active tuberculosis (TB) are excluded
Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
Severe, active co-morbidity defined as follows:* Current (within 28 days of cycle 1, day 1) signs and/or symptoms of bowel obstruction* Patients who require parental hydration and/or nutrition* Patients who require drainage gastrostomy tube* Evidence of bleeding diathesis or clinically significant coagulopathy* Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture* History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment
Pregnant or lactating patients
Patients must have substantial cutaneous neurofibroma burden causing distress to the patient by disfigurement or itching; patients must have >= 9 measurable cutaneous neurofibromas; for the purpose of this study measurability will be defined for each of the lesions selected as target lesions as a neurofibroma with a longest diameter >= 4 mm in the longest diameter
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study
Patients who have received previous investigational agents or biologic therapy, such as tipifarnib, pirfenidone, Peg-intron, sorafenib, or other vascular endothelial growth factor (VEGFR) inhibitors are eligible for enrollment
Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days and are not permitted while on the study
No supplementation with vitamin E is permitted
Known ophthalmologic conditions, such as:* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR)* Current or past history of retinal vein occlusion* Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility * Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
Clinical judgment by the investigator that the patient should not participate in the study
For a clinical diagnosis of NF1 patients must have at least two of the diagnostic criteria for NF1 listed below:* Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)* Freckling in axilla or groin* A neurofibroma or plexiform neurofibroma* Optic glioma* Two or more Lisch nodules* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)* A first-degree relative with NF1
Progressive disease: GIST has demonstrated progression as defined by RECIST v1.1 within the past 12 months; patients whose tumors do not meet this criterion, and have a diagnosis of NF1, may enroll on the NF1 natural history study
There will be no limit to number of prior myelosuppressive regimen for GIST or other tumor manifestations associated with NF1
Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment
Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g. grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism
Patients with evidence of another malignancy or benign tumor requiring chemotherapy or radiation therapy are excluded; however, those patients with a plexiform neurofibroma requiring treatment will be eligible as selumetinib has documented activity in plexiform neurofibromas
Patients with a diagnosis of NF1 and GIST who do not meet other eligibility criteria may enroll on the NF1 natural history study, and will be followed on this study; should they require therapy for GIST based on evidence of progression, they may then enroll on study
Patients who anticipate the need for surgical intervention within the first three cycles (3 months), as surgical intervention during the period of dose limiting toxicity (DLT) evaluation may affect analysis of adherence and/or make the subject inevaluable
Ophthalmological conditions as follows:* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion* Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)* Evidence of optic glioma, malignant glioma, malignant peripheral nerve sheath tumor,* Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study* Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility
No supplementation with vitamin E is permitted because the selumetinib capsules contain vitamin E
Patients must have had cystoscopy confirming no visible papillary tumor within 21 days prior to registration; (CIS disease is not expected to have been completely excised)
Patients must have had cytology within 21 days prior to registration; cytology for patients with CIS component is not expected to be negative for malignant cells; if the cytology for patients with only Ta/T1 disease is positive for malignant cells, patient must have had a biopsy of the prostatic urethra within the previous six months
All patients with T1 urothelial carcinoma must undergo re-transurethral resection of bladder tumor (TURBT) within 60 days prior to registration, and must have uninvolved muscularis propria in the pathologic specimen from either the first or the second TURBT; tissue from the re-resection must be submitted; the TURBT that identified the recurrent T1 disease may have taken place more than 60 days prior to registration
Patients must not have had urothelial carcinoma in the prostate or upper urinary tract within the previous 24 months, or muscle invasive urothelial carcinoma of the bladder at any time; patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis to rule out upper tract malignancy and intra-abdominal metastases within 90 days prior to registration
Patients must be deemed unfit for radical cystectomy by the treating physician, or the patient must refuse radical cystectomy, which is considered standard of care for these patients; the reason for patients not to undergo cystectomy will be clearly documented
Patients must be BCG-unresponsive; a patient is BCG-unresponsive if they meet one or more of the following criteria:* Patient has persistent or recurrent high-grade Ta/CIS urothelial carcinoma after completing therapy with at least induction BCG (>= 5 doses) and first round maintenance or second induction BCG (>= 2 doses)* Patient has high grade T1 urothelial carcinoma after induction BCG (>= 5 doses) only or after induction BCG (>= 5 doses) and first round maintenance or second induction BCG (>= 2 doses)* Patient is disease-free at 6 months after starting BCG (i.e., complete response) but then experiences a high-grade recurrence within 6 months after the last BCG dose
Patients must have a baseline electrocardiograph (ECG) performed within 42 days prior to registration
Patient must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis
Patients must not have severe infections within 28 days prior to registration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
Patient must not have active tuberculosis
Patients must not be known to be allergic to Chinese hamster egg or ovaries
Patients must be offered the opportunity to participate in specimen banking for future studies, to include translational medicine studies
Patient is scheduled to undergo non-small cell lung cancer (NSCLC) resection: video assisted thoracoscopy (VATS) or open thoracotomy for: limited resection, lobectomy, or pneumonectomy; surgery must not be scheduled to take place < 3 weeks after registration
Patient has a doctor diagnosis of COPD
Patient is a current or ex-smoker with a smoking history of >= 10 pack years
Patients must have biopsy-proven newly diagnosed polymorphic or monomorphic PTLD using the World Health Organization (WHO) classification and that is:* CD20 positive* EBV positive by Epstein-Barr virus early ribonucleic acid (RNA) (EBER) in situ hybridization (preferred) and/or LMP immunoperoxidase staining
Patients must be considered medically refractory to decreased immunosuppression (50% or greater reduction) for at least 1 week or there must be documentation in the medical chart that decreased immunosuppression would be associated with an unacceptable risk of rejection
Burkitt morphology
Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence of multi-organ involvement/failure including two or more of the following: * Bone marrow (including pancytopenia without any detectable B-cell proliferation) * Liver (coagulopathy, transaminitis and/or hyperbilirubinemia)* Lungs (interstitial pneumonitis with or without pleural effusions)* Gastrointestinal hemorrhage
Any documented donor-derived PTLD
Pregnant females are ineligible
Patients must have histologically documented unresectable stage III or IV triple negative breast cancer (TNBC) and a known BRCA 1/2 mutation present; TNBC patients must be Her-2 negative, estrogen receptor (ER) negative (defined as less than 3% ER by immunohistochemistry [IHC]) and progesterone receptor (PR) negative breast cancer (defined as less than 3% PR staining by IHC)
Prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) is allowed, provided the following is met: minimum of 6 weeks prior to cycle 1, day 1
Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression)
Patients crossing over from monotherapy to combination therapy do not have to be fully rescreened; however, they do need to meet performance status, organ function, and blood parameters and not meet any of the exclusion criteria
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted if recovered
Prior ACT infusion within 6 months of study enrollment (cohorts include ACT with tumor infiltrating lymphocytes [TIL], human leukocyte antigen [HLA]-class I T cell receptor [TCR]-engineered lymphocytes, HLA-class II TCR-engineered lymphocytes, and chimeric antigen receptor [CAR]-engineered T cells)
Prior ACT therapy should be completed, and residual disease documented by either radiographic progression or active disease observed on biopsy (i.e. hematologic or solid tumor malignancy must be deemed active by the treating investigator); the investigator may deem that the disease is active on the basis of a pre-treatment biopsy demonstrating viable tumor cells or clinical progression of disease (i.e. RECIST progression is not required)
Disease suitable for assessment by pre- and post-biopsies
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with active tuberculosis (TB) are excluded
Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
Patients must have recurrent or refractory disease, or newly diagnosed disease with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:* Ewing sarcoma * Rhabdomyosarcoma (RMS)* Non-rhabdomyosarcoma soft tissue sarcomas (STS) including microphthalmia transcription factor associated STS (alveolar soft part sarcoma [ASPS] and clear cell sarcoma [CCS])* Osteosarcoma* Wilms tumor * Rare tumors ** Medullary thyroid carcinoma (MTC)** Renal cell carcinoma (RCC)** Hepatocellular carcinoma (HCC)** Hepatoblastoma ** Adrenocortical carcinoma** Pediatric solid tumors (including central nervous system [CNS] tumors) with known molecular alterations in the targets of XL184 (i.e., MET amplification, overexpression, activating mutation, MET translocation, MET exon skipping mutations, activating RET mutations, RET rearrangement, overexpression or activation of AXL); documentation of the alteration from a Clinical Laboratory Improvement Act (CLIA) certified laboratory will be required
At least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim
Serum amylase =< 1.5 ULN
Serum lipase =< 1.5 ULN
Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)
Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin, and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) are prohibited* Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted; anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen
Patients with active bleeding are not eligible; specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment; patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with evidence of resolving hemorrhage will be eligible); in patients with CNS tumors, an MRI with ECHO gradient sequences would be required to exclude presence of petechial hemorrhages
Patients who have had significant traumatic injury within 28 days prior to enrollment are not eligible
Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of the study drug are not eligible
Patients must have suspected refractory or relapsed pre-B cell ALL or mixed phenotype acute leukemia (MPAL), or if newly diagnosed, the patient must be 60 years of age or older
Patients must have histologically or cytologically confirmed by the local institution CD19+ precursor B-acute lymphoblastic leukemia (pre-B cell ALL) OR CD19+ mixed phenotype acute leukemia (MPAL): a) with relapse following or refractory to at least one prior line of therapy if older than 21 years; b) in second or higher relapse or refractory to at least two prior lines of therapy if 21 years old and younger (16-21); c) or they must have a new diagnosis of pre-B cell ALL or CD19+ MPAL but are >= 60 years old and are either not a candidate for or do not wish to receive traditional induction chemotherapy
Patients who were treated with blinatumomab in the past will be allowed on the study as long as they have persistent CD19 expression on leukemia cells and did not experience unacceptable toxicities with prior blinatumomab administration; patients who were treated with chimeric antigen receptor (CAR)-modified T cells targeting CD19 in the past will be allowed on the study as long as they have persistent CD19 expression on leukemia cells
Oxygen saturation >= 90% when ambulating and not requiring supplemental oxygen
Active leukemia in the testes or isolated extramedullary relapse; patients with a history of treated leukemia in testes but no active disease at the time of enrollment are eligible
Estrogen receptor (ER) and progesterone receptor (PR) < Allred score of 3 or =< 5% positive staining cells in the invasive component of the tumor (provided the patient is being treated as triple negative breast cancer)
Human epidermal growth factor receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+ according to National Comprehensive Cancer Network (NCCN) guidelines
Activated partial thromboplastin time (aPPT) =< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with active tuberculosis (TB) are excluded
Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
Patients must have normal organ and marrow function independent of transfusion for at least 7 days prior to screening and independent of growth factor support for at least 14 days prior to screening
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients is required; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:* Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)* Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
Body weight > 30 kg
Receipt of prior radiotherapy or condition for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician
History of active primary immunodeficiency
Known history of previous clinical diagnosis of tuberculosis
Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational treatment or interpretation of patient safety or study results
If post allo-HCT, then patient must have baseline donor T cell chimerism of >= 20% (from peripheral blood); evaluation can be made within 4 weeks of treatment start
No limitations on prior therapies
Patients must have histologically confirmed progressive, metastatic castration resistant prostate adenocarcinoma by meeting ALL the following:* Pathology of prostate gland or metastatic disease must confirm the diagnosis of prostate adenocarcinoma; mixed histology with other variants including but not limited to small cell or neuroendocrine differentiation must be discussed with the study principal investigator (PI) * Metastasis must be documented by radiographic evidence* Castration resistance must be documented with surgical or medical castration with serum testosterone < 50 ng/d (< 2.0 nM); if the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to cycle 1, day 1 and must be continued throughout the study* Progression must be evidenced and documented by any of the following parameters** Two consecutively rising PSA values, above the baseline, at a minimum of 1-week intervals; the minimal value to enter the study is 1.0 ng/ml or greater; the reference value (#1) is the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart; if the PSA at time point 3 (value #3A) is greater than that at point 2, then eligibility has been met; if the PSA is not greater than point 2 (value #3B), but value #4 is, the patient is eligible assuming that other criteria are met, if values 3A or #4 are 1 ng/mL or higher (Prostate Cancer Working Group 3)** Appearance of one or more new lesions on bone scan** Progressive disease by RECIST 1.1
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; patients can be on thyroid hormone replacement medication; asymptomatic patients with elevated thyroid-stimulating hormone (TSH) with normal T4/T3 are allowed to enroll, and recommended to follow with routine thyroid function test especially if they are randomized to cediranib/olaparib arm
Initiating bisphosphonate, or RANKL antibody therapy or adjusting the dose/regimen within 30 days prior to cycle 1 day 1 is prohibited; patients on a stable bisphosphonate regimen are eligible and may continue
Current use of natural herbal products or other �folk remedies�; if using previously, patients must stop using natural herbal products while participating in this study; multivitamin, calcium (Ca)/vitamin D (Vit D) and other vitamin complex supplements are allowed
History of stroke or transient ischemic attack within 6 months of the randomization
NYHA classification of III or IV
Current cardiac arrhythmic condition requiring concurrent use of anti-arrhythmic drug; rate controlled atrial fibrillation is allows
History of hypertensive crisis or hypertensive encephalopathy within 3 years of the randomization
Clinically significant peripheral vascular disease or known abdominal aortic aneurysm ( > 5 cm in diameter) or history of aortic dissection; patients with known history of abdominal aortic aneurysm (AAA) with >= 4 cm in diameter, a repeat ultrasound (US) within the last 6 months prior to randomization will be required to document that it is =< 5 cm, and patient must be asymptomatic from the aneurysm, and the blood pressure must be well controlled as required in this protocol
History of hemoptysis within the last 1 month prior to randomization
Known coagulopathy or bleeding diathesis; those on therapeutic anticoagulation or anti-platelet agent are permitted only after discussing with the study PI
Patients with history of intra-abdominal bleeding or retroperitoneal bleeding within the last 3 years are excluded
Whole blood transfusions in the last 120 days prior to entry to the study
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
Previous enrollment in the present study
NO hepatic artery embolization or cryoablation/radiofrequency ablation of hepatic metastasis within 2 months of study treatment start
No more than 3 prior systemic treatment regimens for advanced PNET
Patients with known manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228) are INELIGIBLE
Progression of disease assessed by local site using Revised Assessment in Neuro-Oncology (RANO) criteria, with plan to administer bevacizumab, either as single therapy or in conjunction with other chemotherapeutic regimens, in order to treat tumor progression/recurrence per the treating physician; patients receiving bevacizumab primarily for reduction of edema (i.e. alleviation of symptoms) rather than for tumor treatment are excluded
Patient must not have planned treatment with immunotherapies (vaccines, checkpoint inhibitors, T-cells); if the patient�s most recent recurrence occurs while on immunotherapy, this must be judged as true recurrence using Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria
For patients with intratumoral hemorrhage (acute, subacute, or chronic) seen on hemosiderin-sensitive (gradient-echo) MRI, there must be at least 10 x 10 x 10 mm measurable enhancement that is not obscured or distorted by magnetic susceptibility blooming artifact
Progressive enhancement (> 25% increase in contrast enhancing volume compared to nadir or a new measurable lesion) on MRI performed within 28 days of registration, and >= 42 days since completion of standard radiation/temozolomide therapy; measurable enhancement is defined as two perpendicular in-plane diameters of at least 10 mm, and at least 10 mm in the 3rd orthogonal direction
Patient must be cleared for bevacizumab administration with respect to any recent surgeries, and post-surgical scans must confirm the presence of measurable residual disease
Patients must be able to tolerate brain MRI scans with dynamic intravenous gadolinium-based contrast agent injections* Ability to withstand 22-gauge intravenous (IV) placement* No history of untreatable claustrophobia* No magnetic resonance (MR) incompatible implants/devices or metallic foreign bodies* No contraindication to intravenous contrast administration** Adequate organ function, including adequate renal function defined as estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73 m^2 as calculated per institution standard of care, and meeting local site requirements for intravenous administration of gadolinium-based MRI contrast agents* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance* Weight compatible with limits imposed by the MRI scanner table
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction; patients can be on thyroid hormone replacement medication; asymptomatic patients with elevated thyroid stimulating hormone (TSH) with normal T4/T3 are allowed to enroll, and recommended to follow with routine thyroid function test
Patients with a history of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or insufficiently treated deep venous thrombosis (DVT) within the past 3 months; Note: Participants with recent DVT who have been treated with therapeutic anti-coagulants for at least 6 weeks are eligible, with the exception of participants being treated with warfarin, which is prohibited on this study; other oral anti-coagulants may be allowed after discussion with overall principle investigator (PI), but short half-life low molecular weight heparins are strongly preferred
Patients with evidence of active bleeding diathesis
Patients with hemoptysis in excess of 2.5 mL within 6 weeks prior to the first dose of study medication
Patients requiring concomitant therapy with phenytoin, phenobarbital, carbamazepine, or valproic acid
For the dose expansion cohort, patients with ovarian, fallopian tube or primary peritoneal cancer must have platinum resistant disease defined as progression within 6 months after last platinum regimen; platinum refractory disease is allowed
For the dose expansion cohort, patients with triple-negative breast cancer may not be BRCA1/2 germline mutation carriers
Any clinically significant electrolyte imbalance, particularly hypokalemia and hypomagnesemia, should be corrected before treatment
Pre-study evaluation must include an ophthalmologic exam by an ophthalmologist (not optometrist) and should minimally include visual acuity testing, slit lamp examination, and funduscopic examination; follow up eye-exams will only be performed if subjects develop/report any visual impairment; visual impairment may include peripheral flashes (photopsia), blurred or double vision, floaters, color distortion and dimness, difficulties with light/dark accommodation, tunnel vision or other field defects, halos, apparent movement of stationary objects, and complex disturbances; follow up eye-exams will minimally include visual acuity testing, slit lamp examination, and funduscopic examination; additional testing will be based on symptoms, what is observed and ophthalmologist recommendations
Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) and with proliferation rate determination, using Ki-67 or MIB-1 immunohistochemistry (=< 30% versus > 30% versus �indeterminate� Ki-67 index)
Patients should be deemed to be potentially eligible and willing candidates for auto-HCT by the enrolling physician
Institution has received results from Adaptive Biotechnologies as defined by one of the following criteria:* Patients are �MRD Indeterminate�: ClonoSEQ ID molecular marker assessment did not identify any unique clonal immunoglobulin DNA sequence OR* ClonoSEQ ID molecular marker assessment identified unique clonal immunoglobulin DNA sequence and MRD assessment is completed
Patients must have achieved a radiologic complete or partial remission as defined by the Lugano criteria
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, and others) are not eligible
Patients with current deep vein thrombosis or deep vein thrombosis within the past 6 months are not eligible
Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C); tumors must be deemed to originate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve)
Presence of deficient (d) DNA mismatch repair (dMMR); MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR; dMMR may be determined either locally or by site-selected reference lab; Note: loss of MLH1 and PMS2 commonly occur together; formalin-fixed paraffin-embedded (FFPE) tumor tissue is required for subsequent retrospective central confirmation of dMMR status
Patients with testing that did not show dMMR (loss of MMR protein) are not eligible to participate; patients whose tumors show MSI-H by polymerase chain reaction (PCR)-based assay are not eligible to participate unless they also have MMR testing by IHC and are found to have dMMR (i.e. loss of one or more MMR proteins)
Patients who are known to have Lynch syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) are eligible to participate
Tumors must have been completely resected; in patients with tumor adherent to adjacent structures, en bloc R0 resection must be documented in the operative report or otherwise confirmed by the surgeon; near or positive radial margins are acceptable so long as en bloc resection was performed. Proximal or distal margin positivity is not permitted
Entire tumor must be in the colon (rectal involvement is an exclusion); surgeon confirmation that entire tumor was located in the colon is required only in cases where it is important to establish if the tumor is a colon versus (vs.) rectal primary
Based upon the operative report and other source documentation, the location of the primary tumor will be categorized as proximal or distal to the splenic flexure (distal includes), and further categorization will be as follows: cecum/ascending, descending, sigmoid colon, or rectosigmoid colon
Thyroid-stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH, if free T4 is normal and patient is clinically euthyroid, patient is eligible
Excluded if known active pulmonary disease with hypoxia defined as: * Oxygen saturation < 85% on room air, or* Oxygen saturation < 88% despite supplemental oxygen
No known allergy to 5-fluorouracil, oxaliplatin, or leucovorin
Tumors within previous radiated field will be designated �non-target� lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with active tuberculosis (TB) are excluded
Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
Evidence of bleeding diathesis or clinically significant coagulopathy
Newly diagnosed and histopathologically confirmed (by central pathology review) potentially resectable soft tissue sarcomas of the extremity and trunk of the following subtypes: liposarcoma (excluding myxoid liposarcoma), leiomyosarcoma and undifferentiated pleomorphic sarcoma* An incisional or core biopsy is the preferred method for diagnosis; fine needle aspiration is not acceptable* Sites permissible for biopsy include** Extremities: upper (including shoulder) and lower (including hip)** Trunk: body wall
Patients must have a sarcoma in the extremity or trunk in location, which is accessible to direct or ultrasound guided injections
Patients with localized sarcomas that are not of the extremity or trunk wall (including head/neck, retroperitoneum, visceral organs, peritoneum, pelvis within the confines of the bony pelvis, and tumors arising in bone)
Patients with grade 1 non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) tumors of any size are not eligible
Patients with evidence of active bleeding or bleeding diathesis will be excluded (patients with excess of 2.5 mL of hemoptysis are not eligible)
Patients requiring therapeutic anticoagulation
Patients with gross total resection of the primary tumor prior to enrollment are not eligible; patients who have experienced tumor recurrence after gross total tumor resection are not eligible
Previous treatment with talimogene laherparepvec (T-VEC) or any other oncolytic virus
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to talimogene laherparepvec (T-VEC) or any of its components
Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis)
Viral infections requiring intermittent or chronic systemic (intravenous or oral) treatment with an anti-herpetic drug, other than intermittent topical use (e.g., acyclovir)
Patients who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec (T-VEC) treatment and through 30 days after the last dose of talimogene laherparepvec (T-VEC)
Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
Patient with and without Down syndrome are eligible and must have one of the following:* Second or greater relapse;* Primary refractory disease with at least 2 prior induction attempts;* First relapse refractory to at least one prior re-induction attempt* Any relapse after HSCT* First relapse with no prior re-induction attempt in setting of Down syndrome* Note: Patients with Down syndrome are eligible with any disease status including first relapse with no prior re-induction attempt; patients without Down syndrome are NOT eligible if in first relapse with no prior re-induction attempt
Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
Patients with any prior history of SOS irrespective of severity
Patients who have been previously treated with inotuzumab ozogamicin
Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
Pathologically confirmed myelodysplastic syndrome (MDS) diagnosis (regardless of initial International Prognostic Scoring System [IPSS] risk category) or oligoblastic acute myeloid leukemia (AML) with 21-30% bone marrow (BM) blasts in whom DNMTi have failed; patients who have developed AML after DNMTi therapy can be enrolled as long as they have initiated DNMTi therapy while they were in the MDS or oligoblastic AML (20-30% BM blasts) phase and the study chair agrees; failure of DNMTis is defined as: failure to achieve a complete response (CR), partial response (PR) or hematologic improvement (HI) after at least 4 cycles of DNMTi or progressed after such therapy
Patients must have no serious or uncontrolled medical conditions
Any patients eligible for allogeneic stem cell transplantation (allo-SCT) and willing to undergo allo-SCT as determined at time of screening for trial; patients who are ineligible or not interested in undergoing allo-SCT will be eligible for the trial
Stage:* any T, N1 (i.e. a palpable mobile unilateral inguinal lymph node), M0, or;* any T, N2 (i.e. palpable mobile multiple or bilateral inguinal lymph nodes), M0, or;* any T, N3 (i.e. fixed inguinal nodal mass or any pelvic lymphadenopathy), M0
Patient is fit to receive the randomization options for which he is being considered
Hematology/biochemistry (as dictated by local hospital practice) should indicate fitness for randomization options and parameters should be in line with considerations specified in the summary of product characteristics; hematological parameters should not be supported by transfusion to enable entry into the trial; liver function and renal function tests must form part of the pre-treatment assessment for patients who may be randomized to receive paclitaxel, ifosfamide, and cisplatin (TIP) chemotherapy e.g. patients with impaired renal function may not be considered for arms B and C of InPACT-neoadjuvant but may be considered for arm A
Willing and able to comply with follow-up schedule
Pure verrucous carcinoma of the penis
Non-squamous malignancy of the penis
Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile)
Newly diagnosed de novo ALL (B-ALL or T-ALL) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-PCR
Known history of chronic myelogenous leukemia (CML)
Patients must have histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)- and HER2-negative (triple-negative, TNBC) or ER, PR, and HER2 equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or endocrine therapies after completion of neoadjuvant chemotherapy; patients who are HER2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines are ineligible; HER2 negative and HER2 equivocal cases as per ASCO CAP guidelines that do not receive HER2-targeted therapy are eligible; patients with weekly ER or PR positive disease, defined as ER and/or PR < 5% by immunohistochemistry, are eligible if the treating physician considers the patient not eligible for adjuvant endocrine therapy; residual disease must be >= 1 cm in greatest dimension, and/or have positive lymph nodes (ypN+) observed on pathologic exam* NOTE: Immunohistochemistry (IHC)-positive isolated tumor cells in the lymph node (N0 [i+]) are not considered node-positive and these patients also must have >= 1 cm residual invasive cancer in the breast in order to be eligible
Patients must be offered the opportunity to participate in specimen banking
Patients must not have a history of (non-infectious) pneumonitis that required steroids or evidence of active pneumonitis
Patients must not be registered to step 2 until receiving confirmation from the Southwest Oncology Group (SWOG) Statistical Center that the patient's tissue specimen was adequate for PD-L1 testing; patients must be registered within 7 days of receiving the e-mail notification confirming submission was evaluable for PD-L1 status
A serum thyroid-stimulating hormone (TSH) must be obtained within 28 days prior to step 2 registration to obtain a baseline value
Patients must have been assigned to S1400F
Prior exposure to CTLA-4 inhibitors (ipilimumab and tremelimumab) is not permitted; prior exposure to the following is allowed: attenuated vaccines, anti-EGFR agents, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
Patients must not have any history of primary immunodeficiency
Patients must not have any known allergy or reaction to any component of the durvalumab (MEDI4736) and/or tremelimumab formulation
Patients must have a thyroid-stimulating hormone (TSH) with reflex free T3/free T4 (if TSH is out of normal range) and electrocardiogram (EKG) obtained within 7 days prior to sub-study registration
Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens
Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor; GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings
For step 1 registration the operating neurosurgeon must provide the modified Simpson grade
GTR must be confirmed on post-operative imaging following the most recent surgery; submission of both pre-operative and post-operative MRIs is required for patients; if a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained; all sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration; imaging subsequent to enrollment must include pre and post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan and an axial T2 fluid attenuated inversion recovery (FLAIR) sequence; to yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness not exceeding 1.5 mm; the post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection; these same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery; computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis
If the patient is a primary English speaker, the patient must participate in the NCF and patient reported outcomes part of the study; if the patient is a primary French or Spanish speaker, the patient must participate in the patient reported outcomes part of the study
NOTE: Central pathology review must occur between steps 1 and 2 of registration; once appropriate pathology specimens are received, central pathology review will occur within 15 days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization
Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma
Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas
Cohort A: Patients must have at least one measurable visceral lesion (per RECIST 1.1); a visceral lesion is any solid organ except for skin, lymph node, and musculoskeletal tissue; at least one of these visceral lesions must be measurable per RECIST 1.1
Cohort B: Patients must not have any visceral lesions
Patients must, in the opinion of the treating physician, be candidates for intralesional administration into cutaneous, subcutaneous, or nodal lesions; patients must have at least 2 injectable lesions
Activated partial thromboplastin time (aPTT) =< 2.0 x IULN if not using anticoagulants within 28 days prior to registration; if using anticoagulants, then the value must be within therapeutic range according to the condition for which the patient is being treated within 28 days prior to registration
Patients must have lactate dehydrogenase (LDH) obtained prior to registration
Patients must not have history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Patients must not have active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) which requires intermittent or chronic treatment with an anti-herpetic drug other than intermittent topical use
Patients must be offered the opportunity to participate in specimen banking for future research
Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child- bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:* Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments* Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Prior treatment with agents targeting the VEGF pathway, including bevacizumab
Presence of leptomeningeal disease
Any contraindication to MRI (i.e. patients with pacemakers or other metal implanted medical devices)
Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
Evidence of bleeding diathesis or coagulopathy (including clinically significant hemoptysis)
History of hypersensitivity active or inactive excipients of AZD9291 (osimertinib) or drugs with a similar chemical structure or class to AZD9291 (osimertinib)
Alanine aminotransferase > 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases; aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Unequivocal evidence of progressive disease on contrast-enhanced brain computed tomography (CT) or MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria, or have documented recurrent glioblastoma on diagnostic biopsy
Only first and second recurrences of GBM are eligible
CT or MRI within 14 days prior to start of study drug
Participants may not have had any prior history of hypertensive crisis or hypertensive encephalopathy
Participants should not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted
Adenocarcinoma of the prostate treated primarily with radical prostatectomy* Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy
One of the following pathologic T-classifications: pT2 or pT3* Patients with positive surgical margins are eligible
One of the following pathologic N-classifications: pN0, pNX* If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus (vs.) extended lymph node dissection) should be noted whenever possible
No clinical evidence of regional lymph node metastasis* Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration* Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1 cm in the short axis
A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mL
No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE) within 60 days prior to step 1 registration* Patients with equivocal or questionable DRE findings should have an MRI of the pelvis to exclude the presence of a prostate fossa mass* Patients with equivocal or questionable exam findings by DRE or MRI are eligible if a biopsy of the lesion is negative for tumor
Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire
Only English and French-speaking patients are eligible to participate
The EPIC-26 must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization
A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7
pT2 with a negative surgical margin and PSA < 0.1 ng/mL
Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration; * Note: The use of finasteride or dutasteride (� tamsulosin) for longer periods prior to prostatectomy is acceptable
Prior allergic reaction to the study drugs involved in this protocol
History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason
Patients must have histologic or cytologic diagnosis of non-melanoma skin cancer (NMSC) or lymphomas other than B-cell lymphomas; as both of those terms are categories rather than specific diagnoses, specific guidance on eligible tumor types is provided below
Patients with T cell and natural killer (NK) cell lymphomas must be refractory to, be intolerant of, have relapsed following, or have refused all standard life-prolonging therapies
Subjects must have at least 1 cutaneous, subcutaneous, or nodal lesion that is suitable for intralesional injection, with or without the use of ultrasound; lesions in mucosal surfaces (periocular, nasal, etc) are not eligible for injection because the area cannot be properly contained with an occlusive dressing
Subjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions
Excluded tumor types* Melanoma* Bone sarcomas* Soft tissue sarcomas, including angiosarcoma, primary cutaneous leiomyosarcoma, dermatofibrosarcoma protuberans* Leukemias* Myeloid sarcoma, leukemia cutis, and chloroma* Hodgkin�s lymphoma* B cell lymphoma
Second primary malignancy, only if it would affect the safety of the treatment or the subject�s ability to complete study-related procedures
Active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis)
Viral infections requiring intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for human herpesvirus 1 (HSV-1) induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Patients must have had ER analysis performed on the primary breast tumor collected prior to neoadjuvant therapy according to current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone receptor testing; if negative for ER, assessment of progesterone receptor (PgR) must also be performed according to current ASCO/CAP Guideline Recommendations for hormone receptor testing
Patients must have had HER2 testing performed on the primary breast tumor collected prior to neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer; patients who have a primary tumor that is HER2-positive, HER2-equivocal, or HER2-negative are eligible
Patients must have a biopsy marker placed within the tumor bed with imaging confirmation (preferably mammogram but ultrasound or magnetic resonance imaging [MRI] is acceptable) of marker placement prior to neoadjuvant chemotherapy
Patients must have achieved a complete or near complete radiologic tumor response on breast imaging with mammogram, ultrasound, and MRI
Patients who have multicentric disease
Patients who are medically unfit to undergo surgical resection
Patients without breast biopsy marker documented by imaging at tumor bed site prior to initiation of neoadjuvant therapy
Patients with one or more of the following imaging criteria from any of the 3 imaging modalities after completion of neoadjuvant chemotherapy (NCT) are not eligible:* Mammogram with malignant appearing calcifications or mass > 1 cm; or* Ultrasound with a hypoechoic area > 2 cm; or* Breast MRI demonstrating a residual mass with rapid rise and washout type III kinetics.
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results
Patients who have previously been treated with talimogene laherparepvec, any other oncolytic virus or pelvic radiation are ineligible
Patients with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to talimogene laherparepvec or any of its components, capecitabine, fluorouracil (5-FU) and / or oxaliplatin are ineligible
Patients with active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) are ineligible
Patients with viral infections requiring intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use are ineligible
Subject who is unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for herpes simplex virus (HSV)-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or children under the age of 1 year, during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec are ineligible
If patients require anticoagulation while on protocol, they should be switched from warfarin to another alternative anticoagulant such as low molecular weight heparin or oral direct factor Xa inhibitors as deemed appropriate by the treating physician for the duration they are on capecitabine (must be switched at least 1 week prior to starting capecitabine) to avoid drug-drug interaction of warfarin with capecitabine
Patients with a known dihydropyrimidine dehydrogenase (DPD) deficiency are ineligible
Patients who are unable to get MRIs due to any reason including pacemakers or automatic implantable cardioverter-defibrillator (AICD) are ineligible
Patients must have recovered from the immediate post-operative period
Patients must have tumor MGMT methylation status of unmethylated as determined by local pathologist using a Clinical Laboratory Improvement Act (CLIA)-approved diagnostic test; results of routinely-used methods for MGMT methylation testing (e.g. methylation-specific [MS]- polymerase chain reaction [PCR] or quantitative PCR) are acceptable
Patients must have baseline MRI performed within the 21 days prior to starting treatment
Patients may not be on coumarin anti-coagulants (warfarin, etc.); heparin, low-molecular weight heparin (LMWH), or other antithrombotic medications are permitted
Patients with gastrointestinal disease, or those who have had a procedure that is expected to interfere with the oral absorption or tolerance of BAL101553 (e.g., functionally-relevant gastrointestinal obstruction, or frequent vomiting unresolved upon anti-emetic supportive care), are ineligible
Presence of diffuse lepto or pachy meningeal carcinomatosis (focal/localized involvement from limited meningeal based metastases acceptable), greater than 1 cm mid-line shift, uncal herniation, or severe hemorrhage/hydrocephalous (small intra-lesional hemorrhage or anticipated surgical cavity is acceptable); patients with seizure at presentation who have been started on levetiracetam and have been stable for 48 hours prior to study registration are eligible at the discretion of treating physician
Patients must not have received prior whole brain radiation therapy; previous SRS/SRT done at least 3 weeks from the planned start of IPdR therapy is acceptable; SRS/SRT/fractionated boosts or neurosurgery can be performed once the dose limiting toxicity (DLT) assessment has been completed, if felt clinically necessary
Patients with primary tumors including germ cell tumor, or lymphoma/leukemia
Patients needing more than 8 mg dexamethasone per day at the time of start of WBRT will not be eligible to participate in the study; however, patients will be allowed entry into the study if it is medically safe to reduce the daily dose of dexamethasone to 8 mg or less from the day of the start of WBRT; the dexamethasone dose for such patients may be increased beyond 8 mg per day during the course of treatment if medically necessary; this increased need for dose should be communicated to the study�s principal investigator, Dr Mohindra at the University of Maryland
Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (World Health Organization [WHO] criteria) are eligible; patients with Burkitt type ALL are NOT eligible
Patients who have BCR-ABL fusion transcript determined by fluorescence in situ hybridization (FISH) or real time-polymerase chain reaction (RT-PCR) or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction; please note: patients must also be assessed for CD20 positivity and other markers; positivity for CD22 and CD20 is defined as baseline expression of the CD22 or CD20 antigen in more than 20% of leukemic cells using local multiparameter flow-cytometric immunophenotyping with the use of CD45 expression as a marker to gate the ALL blast population, according to recommendations from the European LeukemiaNet
No prior therapy for ALL except for limited treatment (=< 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine; however, patients who are being treated with chronic steroids for other reasons (for example, to treat asthma, autoimmune disorders, lupus, etc.) are eligible
No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC
Patients with M2 marrow or better are eligible; patients with M3 or M4 marrow (greater than 25% lymphoblasts) will not be eligible to be randomized* Rating: M0, M1; Blast Cells (%): 0-5.0* Rating: M2; Blast Cells (%): 5.1-25.0* Rating: M3; Blast Cells (%): > 25-50* Rating: M4; Blast Cells (%): > 50.0* The term �blast cell� includes any cell that cannot be classified as a more mature normal element, and includes �leukemic cells,� pathologic lymphocytes, and stem cells
Must have Child-Turcotte-Pugh (CTP) A or B7
Definitive clinical or radiologic documentation of extrahepatic tumor, defined as extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
Uncontrolled prior invasive malignancy, excluding the current diagnosis
Unable to obtain confirmation of payment coverage (insurance or other) for either possible treatment
Tumor O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation status must be available; results of routinely used methods for MGMT methylation testing (e.g. mutagenically separated polymerase chain reaction, MSPCR, or quantitative polymerase chain reaction [PCR]) are acceptable
Patients with a history of bleeding diathesis are ineligible
Patients must have follicular lymphoma (grade I, II or IIIa) confirmed at initial diagnosis and at relapse with identifiable fludeoxyglucose F-18 (FDG) avid disease on PET/CT; patients that have involvement with large cell lymphoma are not eligible
Patients must have a whole body or limited whole body PET/CT scan performed within 42 days prior to registration
All disease must be assessed and documented on the S1608 FDG-PET/CT assessment form
Patients must be able and willing to receive prophylaxis with daily aspirin, low molecular weight heparin, factor X inhibitors or warfarin if randomized to lenalidomide; patients must also be willing to receive pneumocystis jirovecii prophylaxis with sulfamethoxazole/trimethoprim, dapsone, atovaquone or inhaled pentamidine, in the event that they are randomized to TGR-1202; patients unable or unwilling to take any listed prophylaxis are NOT eligible
Patients must be able to discontinue CYP2C9 substrates with a narrow therapeutic index (e.g. warfarin, phenytoin), if randomized to TGR-1202; patients must discontinue such agents at least 1 week or 5 half-lives prior to beginning protocol therapy (whichever is longer)
Patients must have the following components of Follicular Lymphoma International Prognostic Index (FLIPI) available from diagnosis, and collected again at time of registration:* Age* Lactate dehydrogenase (LDH)* Number of nodal groups involved* Serum or plasma hemoglobin * Ann Arbor stageAdditionally, patients must have beta-2-microglobulin collected at time of registration
The trial is open only to women with primary endometrioid adenocarcinoma of the uterine corpus (all histologic grades and stages) who are planned and appropriate for primary surgical treatment
Patients with predominant (> 30%) non-endometrioid histology (such as serous, clear cell, or carcinosarcoma)
Patients with history of thrombophlebitis within the past 2 years or ongoing thromboembolic disorders
Patients must not have previously received a histone deacetylase (HDAC) inhibitor in a clinical trial setting (entinostat, romidepsin, belinostat, panobinostat, vorinostat)
Patients must not be currently taking or have ever taken vorinostat (Zolinza, Merck), panobinostat (Farydak, Novartis) or romidepsin (Istodax, Gloucester Pharmaceuticals)
Patients must not have a history of immune-mediated pneumonitis or colitis that required interruption of therapy or treatment of steroids
Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
Patients must be assigned to S1400G; S1400G biomarker eligibility defined as homologous recombination repair deficiency (HRRD) positive is as follows* Biomarker-positive group** HRRD by FMI*** Homologous recombination repair deficiency by Foundation Medicine Inc., criteria* Alteration type** Truncating mutation, frameshift deletions, indels missense and nonsense mutations predicted to have functional consequence in any of the specified genes* Eligible alteration** Mutation in any one of the following critical HRR pathway genes: ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF, FANCM, NBN (NBS1), PALB2, RAD51, RAD51B (RAD51L1), RAD54L, RPA1
Patients must have achieved stable disease, a partial response, or a complete response at their first disease assessment after initiating first-line platinum-based chemotherapy; patients determined to have progressed (in the opinion of the treating physician) at their first disease assessment are not eligible
Patients must agree to have blood specimens submitted for pharmacokinetic analysis
Newly diagnosed patients must have histologic verification of a primary extracranial germ cell tumor in any of the categories outlined; elevation of serum tumor markers without histologic confirmation is not sufficient for entry on the trial* NOTE: for low risk patients, materials for rapid surgical central review must be sent within 7 days of study enrollment
Able to fluently speak and read English
Followed for cancer or survivorship care at one of the following institutions: * Dana Farber/Harvard Cancer Center* Hospital for Sick Children* Children�s Hospital of Eastern Ontario* Oregon Health and Science University* Seattle Children�s Hospital* Yale University
Has experienced prior or ongoing hearing impairment due to chemotherapy or radiotherapy as defined by one of the following: * Society of Pediatric Oncology (SIOP) grade 1 hearing loss* Subjective (patient-reported) hearing difficulties* Subjective (patient-reported) tinnitus
SR1 and SR2 patients:
Grade II and III gliomas IDH mutant gliomas including; diffuse astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma
Only English or French speaking patients are eligible to participate as the cognitive assessments are only available in these languages
CD4 lymphocyte count is highly encouraged
Patients with infra-tentorial tumors are not eligible
Prior history of neurologic or psychiatric disease believed to impact cognitive function
Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction); note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia
Patients known to have hypersensitivity to dacarbazine (DTIC) are not eligible
The following baseline neurocognitive assessments must be completed and uploaded prior to step 2 registration: HVLT-R (recall, delayed recall, and recognition), TMT parts A and B, and COWA; the neurocognitive assessment will be uploaded into a folder in the NRG Medidiata RAVE System for evaluation by Dr. Wefel; once the upload and scoring of the tools are complete, a notification will be sent within 3 business days to the research associate (RA) to proceed to step 2; in order for the patient to be eligible, at least 5 of the 6 neurocognitive assessments must be able to be scored (i.e. free of any errors)
Completion of all items on the following baseline quality of life forms: MDASI-BT, LASA QOL, WPAI-GH and Employment Questionnaire; these quality of life forms will be required and data entered at step 2 registration
Patients must have evidence of disease progression per RECIST 1.1 prior to enrollment or have evidence of cancer-related pain requiring symptom management with narcotic analgesics
Patients previously untreated or treated with drug therapy for epithelioid hemangioendothelioma (EHE) are eligible; there is no limit on the number of prior regimens used to be eligible
Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject�s safety, obtaining informed consent or compliance to the study procedures
Inability to comply with protocol-required procedures
Women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with platinum-resistant disease (defined as having relapsed within 6 months of last platinum-containing regimen because we would like to include both primary and secondary resistance); patients are allowed to have had more than 2 prior cytotoxic treatment regimens; all patients should have received standard of care agents, which confer clinical benefit
Presence of biopsiable disease and patient able to undergo pre-treatment and on-treatment biopsy
Tissue available from primary and/or recurrent disease to evaluate tumor expression of NY-ESO-1 or PDL1 by immunohistochemistry (IHC) and/or reverse transcriptase-polymerase chain reaction (RT-PCR), and for measurement of DNA methylation
No requirement for tumor expression of NY-ESO-1
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1
Concomitant systemic treatment with chronic use of anti-histamine or non-steroidal anti-inflammatory drugs and other platelet inhibitory agents and patients on oral anticoagulant (e.g. warfarin)
Lack of ability of a patient for immunological and clinical follow-up assessment
Evidence of current drug or alcohol abuse or psychiatric impairment, which in the investigator�s opinion will prevent completion of protocol therapy or follow-up
Unwilling or unable to follow protocol requirements
Any condition which in the investigator�s opinion deems the participant an unsuitable candidate to receive study drug. (i.e., any significant medical illness or abnormal laboratory finding that would increase the patient�s risk by participating in this study)
History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
Patients with active tuberculosis (TB) are excluded
Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
Patients must be scheduled for, or have intent to schedule, a screening mammogram
Patients must be able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol
Patients must not have symptoms or signs of benign or malignant breast disease (e.g., bloody or clear nipple discharge, breast lump) based on physician physical exam or self breast exam; patients with breast pain are eligible as long as other criteria are met
Patients must not have had a screening mammogram within the last 11 months prior to date of randomization
Patients must not currently have breast enhancements (e.g., implants or injections)
ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
To be eligible for inclusion in the annual screening regimen one of the following three conditions must be met in addition to the eligibility criteria above:* Patients are pre-menopausal; OR* Post-menopausal aged 45-69 with any of the following three risks factors:** Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or** Family history of breast cancer (first degree relative with breast cancer), or, participant positive genetic testing for any deleterious genes that indicate an increased risk for breast cancer, or** Currently on hormone therapy; OR* Post-menopausal ages 70-74 with either of the following two risk factors:** Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or** Currently on hormone therapy
Postmenopausal women are defined as those with their last menstrual period more than 12 months prior to study entry; for the purpose of defining menopausal status for women who have had surgical cessation of their periods, women who no longer have menses due to hysterectomy and oophorectomy will be considered postmenopausal; women who no longer have menses due to hysterectomy without oophorectomy will be considered premenopausal until age 52 and postmenopausal thereafter
All other postmenopausal women are eligible for inclusion in the biennial screening regimen
For those women who cannot be assigned to annual or biennial screening at the time of study entry and randomization because they are postmenopausal, have no family history or known deleterious breast cancer mutation, are not on hormone therapy AND for whom a prior mammogram interpretation is not available, breast density will be determined by the radiologist�s recording of it at the time of interpretation of the first study screening examination, either DM or TM; for those who are randomized to TM, radiologists will assign BI-RADS density through review of the DM or synthetic 2D portion of the TM examination; such women cannot be part of the planned stratification by screening frequency and are expected to represent far less than 1% of the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) population
Breast density will be determined by prior mammography reports, when available, or by radiologist review of prior imaging; all other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report
Patients must have a body surface area >= 0.37 m^2 at enrollment while the 120 mg strength tablet supply is available; patients < 0.73 m^2 must follow the dosing nomogram; patients >= 0.73 m^2 at enrollment must follow the dosing nomogram
For subjects with CNS involvement (primary tumor or metastatic disease): Subjects must not have any active bleeding, or new intratumoral hemorrhage of more than punctate size on screening MRI or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621D based on the presence of an actionable mutation; note that treatment assignment may be to primary cohort A for patients with TSC1 or TSC2 loss of function mutations, primary cohort B for patients with other PI3K/MTOR pathway mutations, a histology specific biomarker positive expansion cohort if the criteria to open such a cohort are met, or a biomarker negative expansion cohort if the criteria to open such a cohort are met
Patients who have insulin dependent diabetes are not eligible
Patients with subependymal giant cell astrocytomas (SEGAs) are not eligible
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621 screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol; patients must be enrolled onto a subprotocol within 8 weeks (56 days) of treatment assignment
GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols