Cohort 2 (colorectal cohort) \r\n* Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than 3 months prior to study enrollment if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as RECIST target lesions, unless there are no other lesions accessible \r\n* Microsatellite stable (MSS) tumor as documented by either: \r\n** Immunohistochemistry (IHC) testing that does not suggest loss of MLH-1, MSH-2, PMS2 or MSH6 \r\n** Polymerase chain reaction (PCR) testing that does not suggest microsatellite instability (MSI)
Tumor verified by a thoracic surgeon to be in a location that will permit sublobar resection
Tumor located peripherally within the lung; NOTE: peripheral is defined as not touching any surface within 2 cm of the proximal bronchial tree in all directions; patients with non-peripheral (central) tumors are NOT eligible
Received a current diagnosis of borderline epithelial ovarian tumor (formerly tumors of low malignant potential)
Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably collected within the last 3 years) of nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies.
Direct tumor extension into the stomach, duodenum, small bowel or large bowel
Inclusion criteria:\n\n        Subjects must satisfy all the following inclusion criteria to be enrolled in the study:\n\n          1. Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent\n             Form(s).\n\n          2. Stage IV pancreatic ductal adenocarcinoma (PDA) with histological or cytological\n             confirmation of PDA.\n\n          3. Subjects must be determined to be HA-high based on archived or fresh tumor core biopsy\n             or sample obtained after the subject has documented metastatic disease.\n             Biopsies/samples must meet the following requirements:\n\n               1. Pancreas tumor biopsies/samples obtained on or after the date that metastatic\n                  disease is documented or tumor biopsies/samples from a metastatic lesion are\n                  acceptable.\n\n               2. Tumor biopsies or samples must meet the requirements provided in the Study\n                  Laboratory Manual with regard to tumor tissue architecture. Note: cytology\n                  samples from fine needle aspirates without maintained tissue architecture or\n                  brushing biopsies are not acceptable.\n\n               3. Tumor tissue (formalin-fixed paraffin-embedded [FFPE] block preferred) must\n                  include enough tumor to make a minimum of 5-10 unstained, consecutive FFPE slides\n                  (10 slides are preferred) of 1 archival block that meet specific tissue sample\n                  requirements (see Study Laboratory Manual).\n\n          4. Radiographic confirmation of Stage IV PDA with at least 1 tumor metastasis measurable\n             on computed tomography (CT) scan and/or magnetic resonance imaging (MRI) per Response\n             Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, excluding the\n             primary pancreatic lesion.\n\n          5. If a subject has had adjuvant/neoadjuvant therapy and/or therapy for locally advanced\n             disease (chemotherapy for non-metastatic pancreatic cancer in combination with or\n             without radiation therapy), tumor recurrence or disease progression must have occurred\n             no sooner than 6 months after completing the last dose of the aforementioned\n             therapies, provided all toxicities have returned to baseline or ? Grade 1.\n\n          6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.\n\n          7. Life expectancy ?3 months.\n\n          8. Age ?18 years.\n\n          9. A negative urine or serum pregnancy test within 7 days before Cycle 1, Day 1 (C1D1;\n             first dose of study medication) if female subject is of childbearing potential.\n\n         10. Screening clinical laboratory values as follows:\n\n               1. Total bilirubin ?1.5 times upper limit of normal (ULN) (subjects with Gilbert\n                  syndrome are eligible independent of bilirubin levels).\n\n               2. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine\n                  aminotransferase (serum glutamic pyruvate transaminase) ?2.5 times ULN, (if liver\n                  metastases are present, then ?5 times ULN is allowed).\n\n               3. Serum creatinine ?2.0 mg/dL or calculated creatinine clearance ?40 mL/min.\n\n               4. Serum albumin ?2.5 g/dL.\n\n               5. Prothrombin time or international normalized ratio (INR) within normal limits\n                  (±15%), unless subject takes warfarin, in which case prothrombin time or INR\n                  result must be within therapeutic range.\n\n               6. Partial thromboplastin time (PTT) within normal limits (±15%).\n\n               7. Hemoglobin ?9 g/dL (transfusion and erythropoietic agents allowed).\n\n               8. Absolute neutrophil count ?1,500 cells/mm3.\n\n               9. Platelet count ?100,000/mm3.\n\n         11. For women of childbearing potential (WOCBP) and for men, agreement to use a highly\n             effective contraceptive method from the time of screening throughout the study until 1\n             month (WOCBP) or 6 months (men) after administration of the last dose of any study\n             medication. Highly effective contraceptive methods consist of prior sterilization,\n             intrauterine device (IUD), intrauterine hormone-releasing system (IUS), oral or\n             injectable contraceptives, barrier methods, and/or true sexual abstinence.\n\n        Exclusion criteria:\n\n        Subjects are ineligible for enrollment if they meet any of the following exclusion\n        criteria:\n\n          1. Clinical evidence of deep vein thrombosis (DVT), pulmonary embolism (PE) or other\n             known TE event present during the screening period.\n\n               1. Subjects with superficial vein thrombosis are eligible.\n\n               2. Subjects with visceral/splanchnic vein thrombosis are still eligible if, in the\n                  opinion of the Investigator, the visceral/splanchnic vein thrombosis is primarily\n                  associated with the anatomic location of the underlying disease of metastatic\n                  pancreatic cancer.\n\n          2. Previous radiotherapy, surgery, chemotherapy, or investigational therapy for the\n             treatment of metastatic disease.\n\n             a. Palliative radiotherapy for pain control of metastatic bone lesions is allowed.\n\n          3. Known central nervous system involvement or brain metastases.\n\n          4. New York Heart Association Class III or IV cardiac disease (Appendix C) or myocardial\n             infarction within the past 12 months.\n\n          5. History of cerebrovascular accident or transient ischemic attack.\n\n          6. Clinically significant pre-existing carotid artery disease.\n\n          7. Known infection with human immunodeficiency virus, or active infection with hepatitis\n             B or hepatitis C within the past 12 months.\n\n          8. Known allergy to hyaluronidase.\n\n          9. Current use of megestrol acetate or megestrol acetate-containing drugs (use within 10\n             days of Day 1).\n\n         10. Contraindication to heparin as per institutional guidelines.\n\n         11. Women currently pregnant or breastfeeding.\n\n         12. Intolerance to dexamethasone.\n\n         13. History of another primary cancer within the last 3 years with the exception of\n             non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical\n             carcinoma in-situ.\n\n         14. Any other disease, active, uncontrolled bacterial, viral or fungal infection requiring\n             systemic therapy, metabolic dysfunction, physical examination finding or clinical\n             laboratory finding that leads to reasonable suspicion of a disease or condition that\n             contraindicates the use of an investigational drug, or that may affect the\n             interpretation of the results, or that may render the subject at high risk for\n             treatment complications.\n\n         15. Immunization with a live vaccine up to 2 weeks prior to Day 1.\n\n         16. Hypersensitivity to the active substance or ingredients of PEGPH20, gemcitabine, and\n             nab-paclitaxel.\n\n         17. Inability to comply with study and follow-up procedures as judged by the Investigator.
Prior gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is allowed but the subject must have either histopathologic confirmation of recurrent tumor, or new enhancement on MRI outside of the radiotherapy treatment field
IDH mutation status of the primary tumor must be available or tumor samples must be available for pre randomization testing
A contrast enhancing brain tumor that is any of the following:
Rectal tumor at baseline which would be considered to require complete TME
Primary unresectable rectal cancer; a tumor is considered unresectable when invading adjacent organs and an en bloc resection will not achieve negative margins
Angiosarcoma tumor specimen, if available
Presence of tumor(s) invading into the heart or great vessels (including carotid artery) or another location where bleeding is associated with high morbidity including patients with primary cardiac or great vessel angiosarcoma
At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
Central nervous system (CNS) embryonal tumor other than medulloblastoma or PNET in the posterior fossa, for example, patients with diagnosis of atypical teratoid/rhabdoid tumor (ATRT), supratentorial PNET, pineoblastoma, ependymoblastoma, embryonal tumor with abundant neuropil and true Rosettes (ETANTR) are excluded
Tumor size > 3.5 cm
Tumor assessment for FGF/FGFR gene alteration status.
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:\r\n* By pathologic evaluation, primary tumor must be pT1-3\r\n* By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN2b, pN3a, or pN3b\r\n* If pN0, pathological tumor must be >= 3.0 cm
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)
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)
Tumor is causing symptomatic bowel obstruction (patients who have had a temporary diverting ostomy are eligible)
Patients must have tumor slides available for submission for HER-2 testing; HER-2 testing must be completed by the central lab prior to step 2 randomization
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
Patients must not have cavitating pulmonary lesions; patients must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
Patient’s baseline imaging must not indicate the presence of tumor invading or encasing any major blood vessels
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
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\r\n* NOTE: for low risk patients, materials for rapid surgical central review must be sent within 7 days of study enrollment
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, per the operative and/or pathology report, positive margin(s) (tumor present at the cut or inked edge of the tumor) which is not superceded by an additional margin of tumor-negative tissue, nodal extracapsular extension, and/or gross residual disease after surgery are not eligible
Per the operative report, the gross total resection of the primary tumor with curative intent was completed within 8 weeks prior to randomization
Patients with the following characteristics (depth of stromal invasion and lymphovascular space involvement to be pathologically confirmed):            \r\n* Positive capillary-lymphovascular space involvement and one of the following:                \r\n** Deep third penetration\r\n** Middle third penetration, clinical tumor >= 2 cm\r\n** Superficial third penetration, clinical tumor >= 5 cm\r\n* Negative capillary-lymphatic space involvement                \r\n** Middle or deep third penetration, clinical tumor >= 4 cm
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
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
No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass
Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:\r\n* Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin\r\n* 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\r\n* No prior tumor resection or biopsy
Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes\r\n* Group A1:\r\n** > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR\r\n** Patients less than 6 months of age with an adrenal primary tumor > 3.1 and < 5 cm in greatest diameter OR\r\n** < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter\r\n* 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:\r\n* 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\r\n* No prior tumor resection, tumor biopsy ONLY\r\n* 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
Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study
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
The tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed)
Any site of distant disease (for example, drop metastases from the GBM tumor site)
Postoperative tumor plus surgical bed size exceeds 5 cm in maximum diameter
Pathologic evidence of active primary disease or local/regional breast tumor recurrence at the time of registration;
Patients must have had all visible tumor resected completely within 60 days prior to registration; CIS disease is not expected to be completely excised; all patients must have tumor tissue from the histologic diagnosis of recurrence available for central pathology review submission; failure to submit these materials will make the patient ineligible for this study
Patients with histologically confirmed ovarian stromal tumor [granulosa cell tumor, ganulosa cell-theca cell tumor, Sertoli-Leydig cell tumor (androblastoma), steroid (lipid) cell tumor, gynandroblastoma, unclassified sex cord-stromal tumor, sex cord tumor with annular tubules]
Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment; tumor may have originated in any primary site\r\n* 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)
Patient has had previous treatment with the study drug or other Wilms' tumor 1 (WT1)-related immune therapy
Histologically confirmed diagnosis of inoperable PVNS/ dt-TGCT or potentially resectable tumor that would result in unacceptable functional loss or morbidity as determined by a qualified surgeon or multi-disciplinary tumor board (must be documented in the CRF during screening)
Germ cell tumor (GCTs), excluding immature teratoma, or teratoma with malignant transformation.
Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. Patient must be willing to undergo a new tumor biopsy at baseline or at molecular pre-screening if applicable, and during therapy on this study. For patients in the phase II part of the study, exceptions may be granted after documented discussion with Novartis. After a sufficient number of paired biopsies are collected, the decision may be taken to stop the collection of biopsies.
Subjects must have measurable disease as demonstrated by residual abnormal tissue at a primary or metastatic site (measurable on CT or MRI) at the time of biopsy; tumor must be accessible for biopsy. In addition, subjects with bone or bone marrow only disease expected to be >75% tumor are eligible to enroll.
Primary tumor site: oral cavity, oropharynx, larynx, hypopharynx
Greatest tumor dimension of all sites must be =< 5.0 cm or < 250 cm^3
Women with histologically proven invasive breast cancer without distant metastases; a clinical tumor classification of tumor size must be at least 1 cm with or without clinical pathologic evidence of positive nodes
Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels (Note: tumor abutting the vessel is acceptable, but contiguous tumor and vessel is not; CT with contrast is strongly recommended to evaluate such lesions)
CNS GCT including pure germinoma and MMGCT; patients with histologically proven germinoma and MMGCT, including endodermal sinus tumor (yolk sac tumor), embryonal carcinoma, choriocarcinoma and mixed germ cell tumor will be eligible for the study; patients with mature/immature teratoma who have tumor marker elevations are eligible on this study; patient with ONLY mature and/or immature teratoma are ineligible in the absence of the tumor marker elevations
Patients with the diagnosis of mature or immature teratoma in the absence of tumor marker elevations are excluded from the study
Subjects with histopathologic confirmation of intermediate or high-grade primary central nervous system lymphoma (PCNSL) as documented by brain biopsy, or cytology (analysis from cerebral spinal fluid [CSF] or vitrectomy), and cluster of differentiation 20 (CD20) positive; whenever possible, the tumor should be characterized by immunophenotype
Presence of greater than 1 cm x 1 cm residual tumor enhancement on postoperative MRI;
PHASE I (STRATUM 1): Patients with a histologically confirmed diagnosis of a primary CNS tumor that is recurrent, progressive, or refractory; all tumors must have histologic verification of HGG, medulloblastoma, CNS embryonal tumor (NOS), ependymoma, or ATRT; patients with low-grade gliomas are excluded
PHASE I (STRATUM 1): Patients with progressive DIPG, as defined by progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid toxicity wean, electrolyte disturbances, sepsis, hyperglycemia, etc.), OR an increase in the bi-dimensional measurement, taking as a reference the smallest disease measurement recorded since last treatment, OR the appearance of a new tumor lesion since diagnosis \r\n* Please note:\r\n** Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation\r\n** Patients with pontine lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of malignant glioma WHO II-IV. These patients must have radiographic evidence of progression
SURGICAL STUDY (STRATUM 2): Patients must have recurrent or refractory disease with a histological diagnosis at either the time of diagnosis or at the time of recurrence of one of the following: \r\n* HGG\r\n* Medulloblastoma, \r\n* CNS embryonal tumor (NOS), \r\n* Ependymoma, or \r\n* ATRT
Willingness to undergo serial tumor biopsies before and on treatment
Participants enrolled must have disease that is accessible for tumor biopsies and must agree to a pre-treatment tumor biopsy
Resection of at least 80% of the volume of the tumor is feasible; resectability will be determined by the surgeon and radiologist after discussion among the multidisciplinary team
Tumor is deemed to be resectable with negative margins by conventional surgical standards
Tumor lesion accessible for biopsy after the start of treatment. (Note: this lesion should be separate from measurable lesions that will be used for response assessment.)
At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
Patients may not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy
The maximum radiation target volume for GTV3 is 65 cc (per NRG Oncology guide); patient may be excluded after the first sMRI scan if the GTV3 volume is greater than 65 cc (we anticipate that contrast-enhancing tumor volume [residual tumor volume following tumor resection] would be less than 20 cc)
Patients must agree to have a biopsy of metastatic tissue at baseline, and there must be a lesion that can be biopsied with acceptable clinical risk (as judged by the investigator)\r\n* Patients with unsuccessful baseline biopsies may undergo an additional biopsy attempt (at the same or a different site, determined by the investigator)\r\n* For patients with an intact primary and no metastatic site that can be safely biopsied, biopsy of the primary is acceptable, but must be approved by the principal investigator\r\n* Baseline tumor biopsy may be omitted if the tumor is inaccessible and/or a biopsy is not thought to post exceptionally high procedural risk due to location or other factors
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
Subjects enrolling to the phase 1 portion of the trial who have received a prior RET TKI must be able and willing to undergo a pre-treatment fresh tumor biopsy
Subjects enrolling to cohort B or C of the phase 2 portion of the trial who have received a prior RET TKI must be able and willing to undergo a pre-treatment fresh tumor biopsy
Patients are required to have an activating ALK aberration in their tumor detected by certified assay (i.e. CLIA in the US.) prior to registration. The report from this test is required to be submitted for eligibility. Patients with at least one of the following genetic features in their tumor will be considered to have an activating ALK aberration:
To be enrolled in the dose escalation or in the MTD expansion, Subject must have a locally confirmed diagnosis of either of the following tumor types:
Upon the identification of an MTD or RP2D, the Sponsor, in consultation with the study investigators, may open the enrollment of two of the following nonrandomized tumor specific extension cohorts:
For the MTD expansion cohort, Subject must have an accessible tumor lesion(s) and consent to tumor biopsy of such a lesion(s) during screening and after starting KO-947 treatment.
The tumor must have been determined to be microsatellite stable (MSS).
The Sponsor may decide to limit the specific tumor types selected or treatment settings for specific arms based on evidence gathered.
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Tumor deposits that are clearly accessible for serial tumor biopsies - a patient’s biopsied lesion must be at least 1 cm in diameter (in at least one dimension)
Phase 2 only: Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy
Be willing and able to undergo a core or excisional tumor biopsy according to institutional standards (guided visually or by computed tomography [CT] or ultrasound), paracentesis, or thoracentesis for tumor cells \r\n* Note: This is to be done prior to treatment at C1D1 and post-treatment (cycle 2 day 8), if this is clinically and safely feasible to do so; this will allow the use of this freshly obtained tissue for correlative analyses in the study
Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at baseline, and again during therapy on this study.
Available tumor sample for testing
Patient is willing to undergo a fresh tumor biopsy (core or excisional) for correlative analyses (ie. PD-L1 expression)
Confirmed availability of representative tumor specimens
Subjects must agree to undergo tumor biopsies until biopsies have been obtained from 20 subjects (i.e., biopsies are required in at least the first 20 enrolled subjects, or until a goal of 20 study biopsies are obtained); subjects in whom a biopsy is technically not feasible or in whom would result in unacceptable risk in the opinion of the investigator, may be exempted from the biopsy requirement with discussion with the principal investigator
The size of the Grade IV glioma tumor is multi-focal and > 30mm in size, as assessed at the baseline (pre-study) MRI evaluation.
Patients must have evidence of recurrent or metastatic carcinoma by one or more of the following:\r\n* The appearance of metastatic disease by standard imaging techniques\r\n* The appearance of rising serum tumor marker, AFP or beta-hCG\r\n* NOTE: If a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least one week apart are needed; patients with only evidence of disease is rising tumor marker AFP and beta-hCG will be provided alternate causes of increased serum levels of these markers are not present, such as cross reaction with luteinizing hormone (LH) (that can be tested if needed by testosterone suppression of LH), hepatitis, use of marijuana or second primary tumor, etc
Group A: Subjects with any solid tumor (including lymphomas).
Patients must have archival tumor tissue or agree to a tumor biopsy for mutation and biomarkers analysis unless previously discussed with sponsor's medical monitor or its designee (fresh tumor biopsies are recommended at baseline in patients with readily accessible tumor lesions and who consent to the biopsies). Patients with ovarian, fallopian tube, primary peritoneal, or breast cancer in Part A and all patients enrolled in Part B must also agree to provide fresh blood sample at the baseline for the evaluation of BRCA mutations and/or confirmation of prior BRCA results or other homologous reconstitution deficiency mutation even if it was previously tested.
Patients must have radiologic evidence of recurrent, refractory or progressive malignant central nervous system (WHO grade III or IV) or solid tumor; for patients with radiologic features of DIPG histologic confirmation of diagnosis is not required though biopsy is suggested if clinically indicated
Diagnosis of metastatic or advanced CRC, UCC, SCCHN, salivary gland cancer or NSCLC with tumor accessible for biopsy
Willing to consent to tumor biopsies during the study
For Part A exclusively (RO6874281 monotherapy), confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of location accessible to biopsy per clinical judgment of the treating physician, and confirmed progression at baseline; for whom no standard therapy that would confer clinical benefit to the participant exists
Molecular testing results from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories used for patient eligibility should be obtained from the most recent tumor biopsy (baseline tumor biopsies and on-progression tumor biopsies are optional)
Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
Primary breast tumor size at least 2 centimeter (cm) in one dimension by clinical or radiographic exam; patients who have multicentric breast cancer are eligible if each lesion is ER-negative and HER2-negative; in that case, one lesion needs to be identified as the index lesion to be followed for clinical response; the index lesion must also be the lesion from which core biopsies are obtained
For patients enrolled on Phase 2 of study at UCSF, tumor biopsy is required in the subset of patients who have a metastatic lesion amenable to biopsy in the judgment of study investigator and Interventional Radiology
Primary spine tumor
BRAF mutation in loci other than V600 (BRAF nonV600 MUT) or BRAF fusion detected by genetic testing of the primary tumor or regional/distant metastasis
Subjects must provide either a fresh or archived tumor sample for correlative study analyses
The subject has tumor in contact with, invading or encasing any major blood vessels
The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Tumor size ?1.5 cm in greatest diameter in the axis parallel to the treatment probe AND ?1.5 cm in the axis anti-parallel to the treatment probe AND ?1.5 cm in Anterior/ Posterior dimension. Tumor size ?1.5 cm in greatest diameter as measured by breast ultrasound, mammogram and/or MRI. The largest dimension measured will be used to determine eligibility.
All patients must have had an MRI of the brain and spine that has measurable tumor (not only diffuse leptomeningeal tumor) within two weeks prior to study enrollment; Note: central review of MRIs is required, but may be completed concurrently with patient registration; completion of central review is not required prior to starting treatment
Evidence of hormone sensitive, ER rich primary tumor defined by an Allred score of >= 6
Macrovascular tumor invasion.
Patient must have unresectable primary tumor or metastases (including tumors with an intralesional resection)\r\n* For Stratum 1, patients must have a confirmed histologic diagnosis of osteosarcoma\r\n* For Stratum 2, any histologically confirmed solid tumor diagnosis is eligible
Is willing to provide and there is confirmed availability of pre-existing diagnostic or resected tumor samples, such as paraffin-embedded sections. Providing fresh tumor biopsy is optional for subjects in Dose Escalation cohorts.
Has a tumor that contains a nonsynonymous mutation, insertion, or deletion in the TP53 gene determined previously or at screening.
Participants must have histologically confirmed well differentiated or moderately differentiated neuroendocrine tumor from either a primary or metastatic site; carcinoid tumors of any primary site are eligible
PIK3CA MUTANT COHORT (closed 03/17/2016): Tumor PIK3CA mutation present
Must have biopsy-proven desmoid tumor (or aggressive fibromatosis). For patients with recurrent disease, a biopsy is not required at the time of recurrence
Dental braces or prosthesis that interferes with tumor imaging
Tumor in a location where enlargement could cause airway obstruction
The subject has tumor invading or encasing any major blood vessels
The subject has evidence of clinically significant bleeding from tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
For Arm A, patients must have disease that is amenable to biopsy and must be willing to provide consent for a tumor biopsy at baseline (within 30 days of beginning ONC201) and at least 1 on-treatment tumor biopsy.
Uncontrolled tumor-related pain
Have evidence of homozygous loss of CDKN2A or MTAP in the subject's tumor tissue.
Has one of the following tumor locations/types:1) NSCLC involving the superior sulcus; 2) Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
HER2-positive (immunohistochemistry score 3+) or ERBB2- amplification (ratio ERBB2/centromeres >= 2.0 or mean gene copy number >= 6) on primary tumor or of metastatic or unresectable loco-regional biopsy.
Must be able and willing to undergo mandatory tumor biopsy.
Limited disturbance of tumor during biopsy.
Tumor Treatment Field (TT Fields) therapy allowed.
Known to be T790M+ (on pre-treatment tumor or plasma) or known germline T790M
Participants with a maximum tumor diameter exceeding 5 cm (if not resected)
Has an evaluable baseline tumor sample to submit for analysis.
Primary tumor size > 1 cm
Untreated and uncontrolled second tumor in the past 2 years
Part A: subjects must have a FFPE tumor sample available (e.g., from their prior surgery) that is suitable for the next generation sequencing (NGS) required for this study
Part B: subjects must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry and provide a biopsy suitable for the NGS required for this study.
Main portal vein tumor thrombosis
A pretreatment research core biopsy of the primary tumor must be performed with submission of 2 cores for required correlative studies. These specimens will NOT be returned to the site.
Able to provide a sufficient amount of representative tumor specimen for central laboratory testing of RAS mutation status and microsatellite stable (MSS).
Availability to provide a representative tumor specimen biopsy
Uncontrolled tumor-related pain
Participant must be willing to undergo tumor biopsies prior to treatment and on Cycle 2 Day 1. In the Phase 2 part of the trial, participants with bone-only disease, or participants for whom a biopsy is contra-indicated, may opt out of providing tumor biopsies. Note: A subset of participants in Phase 2 will be required to provide tumor tissue until tumor pairs have been collected from at least 15 ER?WT and 15 ER?mut (determined by sponsor-designated central laboratory test).
Primary breast tumor size of greater than (>) 2 centimeters (cm) by at least one radiographic or clinical measurement
Biopsy proven neuroendocrine tumor, which is somatostatin receptor positive as demonstrated on somatostatin receptor PET\r\n* All sites or origin are eligible\r\n* Functional and nonfunctional tumors are allowed
Any patient with suspected brain tumor on diagnostic MR imaging who will undergo a resection
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: MTD expansion: Patients must be willing to undergo pre- and on-treatment tumor biopsies; patients are exempt from this requirement if, in the opinion of the investigator, the biopsy procedure would pose a significant risk or if they have only pulmonary metastatic disease
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: MTD expansion: Patients currently taking anticoagulants and who cannot safely hold the medication to facilitate pre and on-treatment tumor biopsies are excluded from participation
Participants with tumor =< 1 cm proximity to the ventricles will be allowed to enroll; however the study agent (rQNestin34.5v.2) may not be injected in any area that is within 1 cm of the ventricle regardless of where the tumor is located
Tumor accessible for biopsies and agreement to conduct pre-dose and post-dose fresh tumor biopsies.
Part 2, Cohort 4, Any histologically-confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective. Must have accessible tumor tissue and be willing to undergo tumor tissue sampling (biopsies/aspirates) pre- and post-treatment
Known to be T790M+ (on pre-treatment tumor or plasma) or known germline T790M
For Ph1a monotherapy and combination cohorts, histologic or cytologic confirmation of advanced solid tumor.
Tumor accessible for unrestricted illumination for photodynamic therapy (PDT) (accessibility as determined by the physician)
Previous treatment in the target tumor area
Greater than 50% tumor burden in the liver by imaging.
INCLUSION - TREATMENT: CD5-positive tumor (> 50%) CD5+ blasts by flow cytometry or immunohistochemistry (tissue) assessed in a CLIA certified flow cytometry/pathology laboratory
EXCLUSION - TREATMENT: Tumor in a location where enlargement could cause airway obstruction
Participants with a maximum tumor diameter exceeding 5 cm (if not resected)
At least one tumor lesion with location accessible to biopsy per clinical judgment of the treating physician
Platelets ?70x103/?L (? 70 x 10^9/L) (superficial tumor dosing only)
For deep tumor cohorts, patients who require uninterrupted anticoagulants of any type, on daily aspirin therapy, or NSAIAs.
Patients must be able to undergo appropriate imaging studies to monitor tumor response
Has a tumor(s) in direct contact or encases a major blood vessel, and has ulceration and/or fungation onto the skin surface at the projected injection site.
Patients with pure WDLS, myxoid/round cell or pleomorphic tumor histologic subtypes.
largest tumor volume < 10 cc
longest tumor diameter < 3 cm
Representative formalin-fixed paraffin-embedded tumor specimens from surgical resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death-ligand 1 (PD-L1) expression prior to study enrollment
Optic pathway tumors, including chiasmatic-hypothalamic, tumor without histologic confirmation; patients with chiasmatic lesions with or without contiguous extension of tumor into other regions of the visual pathways demonstrated on contrast magnetic resonance imaging (MRI) will be eligible for study without histopathologic confirmation with or without NF-1
Patients with histologically confirmed diagnosis of a primary central nervous system tumor will be eligible; patient tumors must test positive for the BRAFV600E or the BRAF Ins T mutation at a Clinical Laboratory Improvement Act (CLIA)-approved laboratory; if either mutation cannot be confirmed from a prior test and archival tumor is not available to confirm presence of either mutation, patients must have tumor biopsy to collect tumor sample for mutation confirmation
Available biopsy of primary tumor with adequate samples
Inclusion Criteria:\n\n        Patients must meet all of the following inclusion criteria to be eligible for participation\n        in this study:\n\n          -  Surgical or biopsy-proven diagnosis of WHO grade 3 AA.\n\n          -  Unequivocal evidence of first AA tumor progression or recurrence ? 3 months prior to\n             randomization based on MRI criteria for tumor progression using enlarging Gd-contrast\n             enhancement and/or T2 hyperintensity. Patients with non-measurable Gd contrast\n             enhancing tumors will only be eligible if there is no necrosis seen on MRI and/or\n             histopathological confirmation of AA per standard of care procedures is obtained.\n\n          -  First tumor progression or recurrence following surgical resection or biopsy, if\n             resection is not feasible, EBRT and temozolomide chemotherapy.\n\n          -  Completion of EBRT ? 6 months prior to randomization.\n\n          -  A patient whose AA tumor has progressed or recurred and has had another surgical\n             resection prior to randomization will be eligible if a) pathology review confirms AA,\n             and b) post-surgical MRI demonstrates measurable tumor on T2/FLAIR.\n\n          -  Karnofsky Performance Status (KPS) score of ? 70.\n\n        Exclusion Criteria:\n\n        Patients who meet any of the following exclusion criteria are not eligible for study\n        participation:\n\n          -  MRI defining progression is consistent with a diagnosis of glioblastoma or radiation\n             necrosis.\n\n          -  Patients who are considered to be refractory to EBRT and temozolomide but who have not\n             progressed.\n\n          -  Prior systemic therapy for recurrence of AA.\n\n          -  Presence of extracranial or leptomeningeal disease.\n\n          -  Prior lomustine use.\n\n          -  Any other clinical condition or prior therapy that, in the opinion of the\n             Investigator, would make the patient unsuitable for the study.\n\n          -  Pregnant or breastfeeding.
Any advanced solid tumor, with the exception of colorectal carcinoma (CRC), which is Microsatellite Instability (MSI)-High (MSI-H)
Can supply tumor tissue for study analyses (dependent on tumor type)
Tumor(s) involving the brain stem
Metastatic or unresectable solid tumor malignancy
Agree to provide archival tumor material for research
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): Tumor tissue or circulating tumor deoxyribonucleic acid (DNA) tested positive for HER2 mutation; mutations outside the list will be assessed on a case-by-case basis by the study team to determine eligibility
Cohort C: Patients in this cohort only will require a single tumor biopsy 48-72H after the first administration of IMGN853 and gemcitabine on day 1, cycle 1 of treatment, providing it is safe/feasible and confers non-significant risk to patient
INCLUSION - PROCUREMENT: EBV positive tumor (can be pending)
INCLUSION - INFUSION: EBV positive tumor
Untreated and uncontrolled second tumor in the past 2 years
Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening/ baseline or at molecular pre-screening if applicable, and during therapy on this study.
Pathological diagnosis for the resected tumor demonstrates transformation to higher grade (i.e. WHO grade III or IV) gliomas; if a patient is diagnosed as high-grade glioma (HGG) upon resection after receiving the pre-surgical treatment, the patient will be withdrawn from the study and considered for therapeutic options for HGG (trials for HGG or standard of care); the tumor tissue of such a case would be brought to the lab before the pathological diagnosis is made? and thus would be processed before the lab is informed of the final HGG diagnosis; will evaluate the tumor tissue to help us develop future approaches for HGG
Participants enrolling to the MET cohort who have received a prior MET inhibitor may not be on anticoagulant therapy unless the investigator has deemed it safe to temporarily hold to facilitate the baseline tumor biopsy
Participants enrolling to the NTRK cohort who have received a prior NTRK inhibitor may not be on anticoagulant therapy unless the investigator has deemed it safe to temporarily hold to facilitate the baseline tumor biopsy
TREATMENT EXCLUSION: Tumor in a location where enlargement could cause airway obstruction
Solid tumor located in central lung
Tumor invades a major blood vessel
Submission of research blood draw and/or tumor sample
Patients must have stage cT2-T4a N0 M0 disease; clinical T stage is based on the transurethral resection of the bladder tumor (TURBT) sample, exam under anesthesia and cross-sectional imaging studies; patients must undergo cystoscopy and TURBT as part of the staging procedure within 120 days prior to registration; to exclude non-bulky/low-risk tumors, subjects must have documented muscle invasion with at least one of the following:\r\n* Disease measuring at least 10 mm on cross-sectional imaging; bladder thickening on imaging, by itself, is not adequate\r\n* The presence of tumor-associated hydronephrosis
Patients must have tumor tissues from transurethral resection of the bladder tumor (TURBT) that is within 120 days of registration and available for submission; tissue sample must be sufficient for IHC testing; that is, it must be sufficient tumor tissues for correlative science after pathologic diagnosis (i.e., enough tumor tissue to pass the staging criteria)
Participant’s core biopsy slides suggest that later re-sectioning will not contain sufficient tumor to allow for an adequate evaluation of Ki67 and TUNEL assays, at a minimum
Uncontrolled tumor pain
Participants enrolling to the HR or replicative stress cohorts during stage 1 must have disease that is amenable to biopsy and be willing to undergo a pre-treatment tumor biopsy.
Participants enrolling to the HR or replicative stress cohort during stage 1 may not be on anticoagulant therapy unless the treating investigator has deemed it safe to temporarily hold to facilitate the pre-treatment tumor biopsy.
The tumor must not have an infratentorial component;
Main tumor size > 1 cm
A hypovascular tumor (defined as a tumor with all its parts less contrast-enhanced than the non-tumorous liver parenchyma on arterial phase computed tomography scans)
Phase I: Patients with a site of disease amenable to biopsy, and willing to undergo a new tumor biopsy at screening, and during treatment.
Must have measurable disease by RECIST v1.1, a successful pre-treatment tumor biopsy, and be willing to undergo tumor biopsy during treatment
Tumor positive for EBV encoded RNA (EBER) based on report from certified laboratory.
Patients with T1 primary tumor or T4 large volume tumor that has resulted in larynx dysfunction at baseline (for example tumor largely penetrating into base of tongue and resulting in inability to swallow at baseline)
Part A and Part B: Must be willing to undergo pretreatment and on-treatment core needle or excisional tumor biopsies.
RAS wild-type; both KRAS and NRAS testing are necessary; the presence of pathogenic mutations in KRAS or NRAS is exclusionary; primary tumor or metastatic tumor may be tested
Presence of >= 1 tumor lesion not included as a RECIST 1.1 target lesion which is assessed by investigator and/or radiologist as likely to be amenable to percutaneous biopsy by punch, computed tomography (CT)-, or ultrasound-guided core needle biopsy for serial sampling on treatment
Approximately 1 cm3 preferred but 1 mg minimum of accessible and dispensable tumor (minimum of 3 passes with a core needle)
Insufficient tumor available to produce vaccine
Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
Pathological diagnosis for the resected tumor demonstrates transformation to higher grade (i.e. WHO grade III or IV) gliomas; if a patient who received neoadjuvant vaccines is diagnosed as high grade glioma (HGG), the patient will be withdrawn from the study and considered for therapeutic options for HGG (trials for HGG or standard of care); the tumor tissue of such a case would be brought to the lab before the pathological diagnosis is made; and thus would be processed before the lab is informed of the final HGG diagnosis; because HGG tissue may still reflect the vaccine effects, we will evaluate the tumor tissue to help us develop future approaches for HGG
Patients who have an intact unresected primary tumor should be considered for radical nephrectomy and primary resection prior to enrollment in the study; if the patient is not eligible for surgical resection, the primary tumor must be amenable to SBRT or request for applications (RFA); generally, this will be defined as a primary tumor < 10 cm in size or a primary lesion which can be treated to a dose of >= 8 Gy x 5 without excessive perceived risk of toxicity
Patients must have evaluable tissue/blood for testing as specified by the concurrent FoundationOne criteria; this will be obtained during the standard of care tumor diagnosis and tumor staging evaluation
Neg pregnancy test Part A extension only: • Has a primary tumor or a metastatic site that is accessible for pre- and post-dose biopsy without subjecting patient to high level of risk Part B only:
PHASE I: In order to perform a retrospective biomarker analysis with the next generation gene sequencing UW-OncoPlex assay; fresh tumor biopsies from metastatic or primary tumor lesion will be done if considered safe and feasible by treating physician and radiologist; Patients who already have OncoPlex or other equivalent gene sequencing assay (eg Foundation One, Perthera, Caris etc) test results available from prior tumor biopsy are eligible to participate, without the needed of a repeat tumor biopsy, but the test results need to be provided to the study principal investigator
PHASE IB: Fresh tumor biopsies from metastatic or primary tumor lesions will be done only if considered safe and feasible by treating physician and radiologist; patients who already have OncoPlex or other equivalent gene sequencing assay (eg Foundation One, Perthera, Caris etc) test results available from prior tumor biopsy are eligible to participate, without the needed of a repeat tumor biopsy, but the test results need to be available to the study principal investigator
The tumor site selected for injection cannot have been irradiated within 8 weeks of Cycle 1 Day 1 (C1D1)
May not have a NF1 related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy or surgery
Tumor size (based on evaluation of images or pathology if patient in the post-pathology cohort) must be less than or equal to 3 cm
Tumor suspected or known to invade the esophagus
Documented pCAD expressing tumor cells with the exception of HNSCC and ESCC. An archived tumor sample collected within 36 months prior to baseline if available, or a new tumor biopsy sample must be available for molecular pre-screening.
Consent for a tumor biopsy at screening
Histologic diagnosis of B-Cell NHL. Histology based upon bone marrow biopsies and/or fine needle aspirates as the sole means of diagnosis are not acceptable. All patients must have measurable disease. Any tumor mass of at least 1.5 cm is acceptable.
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\r\nBulk tumor is defined as:\r\n* Tumor with evidence of clinically significant uncal herniation or midline shift\r\n* Tumor with diameter of > 5 cm in one dimension on T2/fluid attenuated inversion recovery (FLAIR)\r\n* Tumor that in the opinion of the site investigator, shows significant mass effect in either the brain or spine\r\n* Multi-focal/ metastatic disease: \r\nNote: A second focus of enhancement in a single FLAIR abnormality is permissible and will not exclude the subject\r\n** Patients with multi-focal parenchymal disease are ineligible\r\n** Patients with leptomeningeal metastatic disease are eligible\r\n* Strata B, D and E – patients whose tumor has a significant component involving the brainstem or with significant fourth ventricular compression are ineligible
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;\r\n* 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\r\n* 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
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:\r\n* Tumor with any evidence of uncal herniation or midline shift\r\n* Tumor with diameter of > 5 cm in one dimension on T2/FLAIR\r\n* Tumor that in the opinion of the site investigator, shows significant mass effect\r\n* 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\r\n* 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)
Low tumor burden as defined by Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria (2):\r\n* No tumor mass (nodal or extranodal) >= 7 cm in one dimension on computed tomography (CT)\r\n* Fewer than 3 (2 or less) nodal masses > 3 cm\r\n* No systemic or B symptoms\r\n* No splenomegaly greater than 16 cm by CT scan\r\n* No risk of organ compression – ureteral, orbital, neurological, gastrointestinal\r\n* No leukemic phase (> 5.0 x 10^9/L circulating FL cells in the blood as detected by complete blood count [CBC] with differential and smear)\r\n* No cytopenias – absolute neutrophil count (ANC) < 1000 or platelets < 100,000
Phase II: if surgical resection/debulking prior to MLA is not indicated, a biopsy of the tumor will be done at the same time of MLA to obtain tumor tissue for both diagnostic purposes and immune monitoring
Patients with metastatic SCCA neck disease with an unknown primary tumor site
ELIGIBILITY FOR SCREENING: EBV positive tumor (can be pending)
At least one endoscopically measurable tumor 6 - 10mm in diameter
-  Confirmed diagnosis of HCC > 10 mm with a characteristic 4-phase CT or dynamic\n             contrast enhanced MRI finding showing intense arterial uptake followed by \washout\ of\n             contrast in the venous-delayed phases per American Association for the Study of Liver\n             Disease (AASLD) criteria.\n\n          -  Patients between ages 20 and 80\n\n          -  Patients with single or multiple (2-4 nodules) HCC who are unsuitable or unwilling for\n             surgical resection or RFA. The largest tumor nodule should be less than 10 cm in the\n             largest diameter. The total volume of tumor cannot exceed 50% of liver; or patients\n             with liver metastatic gastrointestinal cancer, including neuroendocrine tumor\n\n          -  Patients are candidates for TAE or Transarterial ChemoEmbolization (TACE). No tumor\n             invasion to portal vein or thrombosis in portal vein.\n\n          -  ECOG score 0-1 with no known cardiac, pulmonary or renal dysfunction\n\n          -  Child-Pugh score group A or B7 liver functional score\n\n          -  Prior local therapies such as surgical resection, radiofrequency ablation, or alcohol\n             injection are allowed as long as tumor progresses from the prior treatment and the\n             patients are still candidates for TAE. All prior therapy must be at least 4 weeks\n             prior to enrollment and free from treatment-related toxicity.\n\n          -  No TAE/TACE in the past\n\n          -  Patients have normal organ function: ANC ? 1000 /µL, Hemoglobin ? 9 gm/dL, Platelets ?\n             50,000 /µL, Creatinine ? 2 mg/dL, AST and ALT < 5 X upper normal limit of the current\n             institution; bilirubin ? 3.0 mg/dL, PT prolongation no more than 4 sec above upper\n             limit of normal.\n\n        For the expansion cohort of neuroendocrine tumor or metastatic gastrointestinal cancer\n\n          -  Unresectable, locally advanced or metastatic, well differentiated (low or intermediate\n             grade), neuroendocrine tumors (NET).\n\n          -  Liver metastatic gastrointestinal cancer.
Tumor expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) and/or reverse transcriptase polymerase chain reaction (RTPCR)
Patients with a histologic diagnosis of malignant pleural mesothelioma (MPM), epithelioid subtype, who in the opinion of the attending thoracic surgeon can receive a macroscopically complete resection of tumor
Patients with residual enhancing tumor that lies completely within 1-2 cm of the inner table of the skull
Patients must be untreated with curative-intent surgery for current diagnosis of stage III, IVa, or IVb disease; diagnostic biopsy of primary tumor and/or nodal sites is permitted.  \r\n* Diagnostic simple tonsillectomy is permitted, provided patient has Response Evaluation Criteria in Solid Tumors (RECIST)-measurable residual tumor and/or nodal disease\r\n* Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy/radiotherapy), and has not recurred
Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
Willingness to undergo a tumor biopsy at baseline and at disease progression
Cryoablation can be performed near vessels of the head and neck, and if deemed necessary tumor may be displaced using a saline injection (hydrodisplacement); tumor displacement from nerves may be required and will be performed as deemed appropriate to avoid nerve injury
Tumor must be deemed to be inoperable or unresectable either by clinical or radiographic criteria; these criteria include encasement of great vessels, vertebral invasion or undue peri-operative risk
Tumor size not measurable
EBV (+) nasopharyngeal carcinoma in the protocol treated tumor
Surgical arm (Arm A) must be predicted pre-operatively to have sufficiently sized tumor to be resected and provide tissue samples for exploratory assessments.
For dose escalation: Subjects with any type of solid tumor (all comer) will be eligible for dose escalation and dose expansion at MTD in Part 1; Subjects enrolled for dose expansion (MTD expansion cohort \all comer\) will be stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material
Infra-tentorial tumor
The tumor must carry a genetic alteration of ALK
Patient must have an original diagnosis, benefited by autologous transplantation, confirmed by biopsy* of solid tumor, including but not limited to: high-grade glial tumor, low-grade glial tumor, ependymoma, medulloblastoma, primitive neuro-ectodermal tumor (PNET), Wilms' tumor, rhabdomyosarcoma, Ewing's sarcoma, retinoblastoma, or miscellaneous poor-prognosis solid tumors; lymphomas and other lymphoid malignancies will not be studied in this protocol\r\n* Brain stem glioma patients who have progressed after radiation therapy do not require histologic confirmation; brain stem gliomas are defined as intrinsic tumors of the pons causing diffuse enlargement; these patients are diagnosed on clinical and radiographic appearance of the lesion and the biopsy requirement will be waived for this group
Patient must agree, as part of the informed consent, to provide blood and archived tumor samples for molecular correlates, pharmacokinetics and pharmacodynamics; patients in the expansion cohort A must have tumor sites that are accessible for tumor biopsy and must agree to undergo a pre-treatment and post-treatment biopsy; patients in cohort B group 3 and 4 must have tumor sites that are accessible for tumor biopsy and must agree to undergo a pre-treatment and post-treatment biopsy; this requirement may be waived after discussion with the principal investigator as long as a minimum of 5 patients in cohort B group 3 and 10 patients in cohort B group 4 are able to undergo the required biopsies
COHORT A: Patients must have accessible tumor sites for biopsy and must agree to pre-treatment and post-treatment biopsies
COHORT B, GROUP 4: HEAD AND NECK SQUAMOUS CELL CARCINOMA: Patients must not have evidence of major vessel involvement or encasement by tumor; a tumor abutting a major blood vessel may be allowed after review of scans with the radiologist and discussions with the principal investigator (PI)
Patients enrolled at Dose Level 6 or higher in the phase I portion of the trial must have at least one tumor mass suitable and easily accessible for excisional biopsy, or alternatively, accessible for CT or ultrasound guided core needle biopsy. The procedure must be able to be performed with minimum morbidity.
Presence of known or suspected ongoing ischemia of non-tumor tissues including
Patients must have an accessible primary tumor or metastasis, and be willing to have a pre-treatment and post-treatment tumor biopsy (at 6 to 8 weeks after beginning)
Note: Patients may be enrolled more than once (e.g., for a new tumor)
Subjects must have demonstrated either tumor progression or recurrence by any of the radiographic criteria and/or clinical criteria as defined below:\r\n* Subjects with progressive non-resectable disease regardless of location in the brain or spine are eligible for this study; patients with evidence of leptomeningeal dissemination are eligible for this study; patients do not require biopsy/histologic confirmation at the time of progression or relapse\r\n* Radiographic progression is defined as > 40% increase in the product of the three perpendicular diameters of current tumor relative to the baseline measurement (defined as either the initial scan or scan at start of a previous therapy): length (L) x width (W) x transverse (T) (current scan) > 1.4 x L x W x T (baseline scan), or the development of any new sites of disease independent of the response of the initial tumor\r\n* Post radiation changes are often seen on post-treatment imaging studies, so that classification of a patient as having progressive disease may require several serial magnetic resonance imaging (MRI)’s if the child has received radiation within the preceding 12 months\r\n* Tumor volume includes the entire tumor volume seen on gadolinium enhanced T1 magnetic resonance (MR) imaging plus non-enhancing abnormality seen on T2 or fluid attenuated inversion recovery (FLAIR); coronal and axial images will be evaluated\r\n* All tumor cysts will be included in the tumor volume\r\n* Clinical progression without radiographic progression includes children with optic pathway gliomas who demonstrate sustained decrease in visual fields and/or acuity in three serial vision examinations; each of the vision examinations must be performed > 2 weeks apart\r\n* Children with previously negative cerebrospinal fluid (CSF) cytology who show evidence of tumor cells in fluid obtained by lumbar puncture can be designated as having progressive disease in the absence of radiographic evidence of progression
Endometrial cancer\r\n* Patients at a higher risk of recurrence (because of either grade, myometrial invasion, lymphatic vascular space invasion, tumor size, lymph node status, tumor extension, presence or absence of surgical staging)\r\n* Patients who have suffered a recurrence at the vaginal cuff\r\n* Patients who are unable to undergo surgery and must have treatment for an inoperable primary endometrial cancer
Criteria only for the randomized phase 2 part: mesothelin screen positive determined from archival tumor tissue and to be performed centrally. MSLN-positive is defined as >= 30% of tumor cells with membrane staining intensities >= 2+\r\n* For the run-in-phase 1, patients will not be selected based on the mesothelin expression
NSCLC patients with radiographic evidence of major airway or blood vessel invasion by cancer, radiographic evidence of intra-tumor cavitation, or gross hemoptysis (>= one teaspoon) within the preceding 2 months.
Patients with tumor morphology that predicts poor coverage of the majority of the tumor including bilateral thalamic involvement, or cysts that represent > 50% of cross-sectional areas of the pons. These subjects should be discussed with the study chairs.
Subjects with tumor amenable to potentially curative therapy per principal investigator (PI)
Participants must be willing to undergo one mandatory on-study tumor biopsy following a 4 week, single cycle induction treatment of olaparib. A second on-study biopsy at time of disease progression is optional, but not mandatory.
Must have undergone gross total resection of the primary tumor with curative intent within the past 8 weeks with surgical pathology demonstrating >= 1 of the following criteria for \intermediate\ risk of recurrence:\r\n* Perineural invasion\r\n* Lymphovascular invasion\r\n* Single lymph node > 3 cm or at least 2 nodes without evidence of extracapsular extension\r\n* Close margins defined as < 5 mm but not frankly positive (in the case of ambiguous, controversial, or superseded margins, final clinical assessment regarding margin status will prevail)\r\n* Pathologically confirmed T3 or T4 primary tumor.
Largest tumor =< 4 cm.
Must have at least one tumor site accessible for a biopsy
Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
INCLUSION - TREATMENT: Pathologic review shows no evidence of residual disease in the tumor bed (to also include no evidence of residual ductal carcinoma in situ [DCIS])
INCLUSION - TREATMENT: Tumor bed should be no larger than 5 cm in size on pathologic review
INCLUSION - TREATMENT: Fibrotic area of prior tumor located at least 3 mm away from surgical margins
Radiographic, biochemical, or clinical evidence of tumor progression over a period of up to 12 months in at least one site
Has greater than 75% liver parenchyma replacement by tumor
Willingness and ability to undergo mandatory tumor biopsy at baseline
Patients are excluded if they had undergone tumor-­directed therapy within 3 months
Subjects must have an area of tumor amenable to excisional biopsy for the generation of TIL separate from, and in addition to, a target lesion to be used for response assessment.
HER2-expressing tumor (primary tumor or metastasis) as assessed by local lab testing
HER2-positive gastric/GEJ cancer must have received prior trastuzumab, cisplatin (or carboplatin or oxaliplatin or investigational platinum agent) and 5-fluorouracil (5-FU)/capecitabine HER2-Positive Solid Tumor Specific Inclusion Criteria
HER2-positive tumor (primary tumor or metastasis) as assessed by local (non-central) laboratory testing
Have at least 2 tumor lesions accessible for biopsy
Target tumor in region not in previously irradiated field
Subjects must have at least one extra-central nervous system (CNS), non-bone tumor lesion amenable for IT injection ? 1.5 cm and that is not in close proximity or encasing crucial structures such as major blood vessels, trachea, nerve bundles etc.
The primary tumor must be considered resectable by RP with gross negative margins as determined by a urologist. (Applicable to cohorts A and B1 only)
Confirmation of: a) Cohort A: MSI-H CRC either by immunohistochemistry (IHC) for loss of protein expression in one of 4 mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) or by detection of microsatellites within the tumor DNA as per institutional practices; b) Cohort B: CMS4 CRC classification on pretreatment primary tumor; c) Cohort C: MSI-H non-CRC solid tumor either by IHC for loss of protein expression in one of 4 mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) or by detection of microsatellites within the tumor DNA as per institutional practices.
STRATUM C: Participants with recurrent, progressive, or refractory SHH Medulloblastoma and presence of either a or b as confirmed by central pathology review of the tumor specimen: a) copy number loss of 9q b) PTCH1 mutation
For biopsy identified participants: be willing to undergo repeat biopsy of a tumor lesion before and after treatment; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the principal investigator; note: enforcement of biopsy requirement may come into effect for all participants depending on the state of accrual compared with number of obtained biopsies at any point in the study
For patients with oropharyngeal primary site or unknown primary site only: tumoral human papillomavirus (HPV) status must be known, as established by the local site; acceptable standards include p16 immunohistochemistry (where a tumor is classified as p16-positive when showing diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells) and/or assessment of HPV deoxyribonucleic acid (DNA)
Maximal tumor resection has been performed as feasible
All subjects must agree to pre-treatment tumor biopsy; subjects in whom biopsy is technically not feasible or in whom would result in unacceptable risk, in the opinion of the investigator, may be exempted from the biopsy requirement with discussion with the principal investigator
Histological variants in the primary tumor, other than adenocarcinoma; for example: neuroendocrine tumor, small cell or sarcomatoid
Patients must be willing to have archived tumor specimens utilized for correlative studies if available
Has at least 1 measurable solid RCC tumor and no RCC tumor that requires immediate surgical intervention. The diagnosis of RCC can be radiologic (histologic diagnosis not required). Patients may have VHL disease-associated tumors in other organ systems
Subject provides consent for fresh paired tumor biopsy samples to be obtained at screening and after 4 weeks of treatment (not required for run-in cohort or expansion of run-in cohort).
STUDY TREATMENT: An adequate pre-treatment tumor biopsy is required to confirm histologic diagnosis. Acceptable options include laparoscopic biopsy or image-guided core needle biopsy (minimum of two cores). Fine needle aspiration (FNA) biopsy or cytology from ascites is not adequate.
City of Hope (COH) Clinical Pathology confirms HER2+ tumor expression by immunohistochemistry (>= 20%, 1+)
Subjects must have histologically confirmed solid tumor malignancy that is metastatic or treatment refractory cancers which are not curable or do not have known palliative measures or treatments that are associated with a survival advantage (as defined by the subject or the physician investigator); enrollment of subjects with tumors that can be safely biopsied is encouraged
Patient has at least one (1) measurable papillary LG tumor, evaluated visually, ? 15 mm. The largest lesion should not exceed 15mm.
Patient should have at least one remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm.
Ovarian Expansion Cohort: Subjects must have tumor tissue positive (IHC H-score ?150) for Nectin-4 expression
Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a clinical mutation test approved by the local health authority
Uncontrolled tumor-related pain
M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ?1 year from nephrectomy (metachronous).
Tumor test result shows MGMT methylated or indeterminate tumor subtype
Biopsy-only of GBM with less than 20% of tumor removed
Any known tumor outside of the brain
Tumor test result shows MGMT unmethylated type
Any known tumor outside of the brain
Biopsy with less than 20% of tumor removed
PHASE I: Patients with recurrent, refractory, or progressive non-hematologic malignancies (central nervous system [CNS] or solid tumors) associated with activation of the RAS/RAF/ERK pathway, including any LGG, any tumor in a patient with NF1, or any tumor with a documented activating BRAF, NRAS, or KRAS mutation, will be eligible; LGG is defined as any World Health Organization (WHO) grade I or II (or equivalent) astrocytic, oligodendroglial, and/or glioneuronal tumor
PHASE II: Patients with recurrent or progressive disease, as defined in the following three strata below, will be eligible; for eligibility determination, tumor imaging from at least two time-points must be available to document radiographic progression or recurrence; patients with non-progressive refractory tumors will not be eligible \r\n* Stratum 1: patients with LGG with a BRAF truncated fusion that is measurable in at least two dimensions on imaging\r\n* Stratum 2: patients with NF1 and LGG that is measurable in at least two dimensions on imaging\r\n* Stratum 3: pediatric patients with a recurrent or progressive tumor thought to involve the Ras/Raf/ERK pathway but not included in strata 1 or 2 that is measurable in at least two dimensions on imaging; this includes any LGG not included in strata 1 or 2 (i.e., any LGG without a BRAF truncated fusion in a patient without NF1), any tumor other than LGG in a patient with NF1, and any other tumor with a documented activating BRAF, NRAS, or KRAS mutation\r\n* Stratum 4 (surgical arm, target validation): patients who meet criteria for stratum 1, 2, or 3 for whom tumor biopsy and/or resection is clinically indicated
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)\r\n* All patients who are candidates for enrollment in stratum 5 based on their tumor histology must be pre-screened\r\n* Screening may be applied to potential stratum 1 and 2 patients
Patients whose prior BRAF testing was performed at another lab (Clinical Laboratory Improvement Amendments [CLIA]/College of American Pathologist [CAP] certified or otherwise) must send additional tumor material to Brigham and Women's Hospital (BWH) for confirmation; however, to preserve available tumor material, patients whose tumor material has previously undergone BRAF analysis at the Lindeman and Ligon Labs at Brigham and Women’s Hospital using the same procedures as described in this protocol, will not be required to submit additional tumor material for analysis; these patients must have both the BRAFV600E mutation and BRAF KIAA1549 fusion assessments done and if only one test was previously conducted; additional tissue will be required for the second test
Patients with progressive, recurrent or refractory optic pathway glioma, with or without pre-treatment tumor tissue
Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology laboratory and meets any tumor assay profile described in protocol section 4.1.2F
Documentation of Disease:\r\n* Histologic Documentation: Well- or moderately-differentiated neuroendocrine tumors of pancreatic and non-pancreatic (i.e. carcinoid) origin by local pathology\r\n** The pathology report must state ONE of the following: 1) well- or moderately-differentiated neuroendocrine tumor, 2) low- or intermediate-grade neuroendocrine tumor, or 3) carcinoid tumor or atypical carcinoid tumor; documentation of histology from a primary or metastatic site is allowed\r\n** Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid tumor, or goblet cell carcinoid tumor are not eligible\r\n* Stage: Locally advanced/unresectable or metastatic disease\r\n* Tumor Site: Histological documentation of neuroendocrine tumor of pancreatic, gastrointestinal (GI), lung, or unknown primary site; GI, lung, and unknown primary NETs will enroll in the carcinoid tumor cohort of the study\r\n** Functional (associated with a clinical hormone syndrome) or nonfunctional tumors are allowed\r\n* Radiologic Evaluation: Target lesions must have shown evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria in the 12 months prior to registration; the radiologic images, imaging reports, and clinic notes indicating growth of existing lesions, development of new lesions, or treatment changes must be submitted
Evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib, or the subject with radiographic evidence of cavitating pulmonary lesion(s); or subjects with tumor invading or encasing any major blood vessels.
Tumor MGMT promoter deoxyribonucleic acid (DNA) not methylated (i.e., unmethylated) by central testing
Maximal tumor diameter of 6.6 cm or less; patients with multifocal tumors are allowed if the sum of the maximal tumor diameters does not exceed 6.6 cm; note, the maximal tumor diameter for the first 3 subjects enrolled will be 5 cm
Tumor progression after radiation
Infra-tentorial tumor
Willing to undergo a new core or excisional biopsy from a metastatic, not previously irradiated tumor lesion during screening
Tumor sample must be available for HPV p16 and PD-L1 testing and if oropharyngeal, must be tested for HPV p16
Consent to participate in the correlative studies and should have available tumor tissue for tumor biopsies; acceptable biopsies include surgical biopsy, core biopsy or punch/surgical tumor biopsies (of accessible lesions)
Has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years
Pancreatic tumor size ? 5cm
Direct invasion of the duodenum by the primary tumor
Tumor > 2.0 cm, nodal involvement, or metastatic involvement
The tumor must be at least 5 cm in maximum dimension
Tumor accessible for biopsy
No individual tumor size is >50 mm3
Tumor is not impinging on Middle Cerebral Artery/speech-motor strip
If tumor demonstrates EGFR or ALK genomic tumor aberrations, subject should have documented disease progression on FDA-approved therapy for these aberrations
Tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in ? 50% of tumor cells (tumor proportion score [TPS] ? 50%) as assessed by immunohistochemistry at a central laboratory.
Advanced solid tumor malignancy without curative options
The subject has pathologic evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
Patients must have at least one tumor amenable to serial biopsy in clinic or be willing to undergo serial biopsies through image-guided procedures during the neoadjuvant phase of the protocol. Patients must be willing to provide tumor samples at the time points.
Patients must have histologically or cytologically confirmed A) low lying (i.e. =< 6 cm from the anal verge) rectal adenocarcinoma eligible for concurrent chemoradiation therapy to rectal tumor, B) if the treatment is palliative in the metastatic setting, no additional requirements for tumor size or nodal involvement is needed; C) if the treatment is in the neoadjuvant setting, the tumor must ALSO be high-risk locally advanced rectal cancer defined as T3-4, N+, and/or at risk for a positive radial margin (as determined by the surgeon)
Locally advanced/borderline resectable HCC as defined by:\r\n* Solitary tumor > 5 cm OR\r\n* Unilobar multifocal disease either with > 3 tumors or one tumor > 3 cm OR\r\n* Bilobar disease with adequate future liver remnant, still technically resectable OR\r\n* High risk disease features (alpha-fetoprotein [AFP] > 200, or tumor > 3 cm with macrovascular invasion)\r\n* No extrahepatic spread, no nodal disease, and no bilateral left and right branch portal vein involvement
Interval of at least 8 weeks from the completion of radiotherapy; if patients are within 8 weeks of radiotherapy, they may still be eligible if they meet one or more of the following criteria\r\n* Progressive tumor is outside the original high-dose radiotherapy target volume as determined by the treating investigator, or\r\n* Histologic confirmation of tumor through biopsy or resection, or\r\n* Nuclear medicine imaging, magnetic resonance (MR) spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than pseudoprogression or radiation necrosis obtained within 28 days of registration
Patients must agree to submission of tumor blocks or 15-20 formalin-fixed paraffin embedded (FFPE) slides of 5-10 microns in thickness from transurethral resection of bladder tumor (TURBT) and radical cystectomy tissues
Maximum postoperative dimension of cavity plus residual contrast enhancing tumor of < 6 cm; if a patient is found on the radiation planning scan to have a tumor target larger than this size, the patient will be removed from the study
Patients must have a wild type or mutated RAS tumor status known prior to enrollment
Must have a growing tumor amenable to percutaneous image-guided cryoablation based on routine Interventional Radiology criteria
Metastatic poorly differentiated and/or high-grade neuroendocrine tumor/carcinoma originating outside of the lung (including unknown primary)
Patient has symptoms related to hormone production from tumor (i.e. functional tumor)
Biopsy-proven benign or malignant brain tumor requiring tumor bed or tumor irradiation; this may include, but is not limited to, low-grade or favorable high-grade glioma, pituitary adenoma, vestibular schwannoma (acoustic neuroma), and meningioma as the most common diagnoses; other tumor types that require irradiation and are deemed appropriate for proton radiation therapy are also eligible; patients with a presumed diagnosis based on imaging and clinical characteristics will be permitted on this trial without pathological diagnostic confirmation if it is within standard of care to offer radiation therapy without a biopsy
Patients must agree to consent for their tumor samples to be used for generation of cellular research tools such as organoids
Histologically proven malignancy necessitating cranio-spinal irradiation; this will include patients with a diagnosis of medulloblastoma, supratentorial primitive neuroectodermal tumor (SPNET), disseminated ependymoma, embryonal tumor with abundant neuropil and true rosettes (ETANTR), atypical teratoid/rhabdoid tumor (ATRT), and disseminated low-grade glioma (LGG) or histologically confirmed germ cell tumor or elevated alpha-fetoprotein (AFP) (serum > 10 IU/L or cerebrospinal fluid [CSF] > than institutional norm) or B-HCG (serum or CSF > than institutional norm) in the setting of radiographic disease consistent with a germ cell tumor necessitating cranio-spinal irradiation
Patients must have a tumor or plaque that is refractory to conventional treatment including but not limited to one of the following (up to 4 lesions in a single field of PDT or RT will be considered for treatment):\r\n* Plaque stage disease that has failed at least 2 skin directed therapies (including topical steroids) or refractory plaques despite at least one systemic therapy or plaques with evidence of folliculotropism\r\n* The presence of a tumor of MF
Evidence of CD20 expression by immunohistochemistry or flow cytometry on the tumor specimen obtained with the biopsy performed with screening
The tumor must be confined to the supratentorial compartment
The patient must have completed chemoradiation with radiation therapy and temozolomide of the primary tumor according to standards of care
Tumor diameter in the plane perpendicular to LITT trajectory must be =< 3.5 cm in diameter
It must be the surgeon’s expectation that >= 90 of the tumor can be treated with LITT to the yellow TdT line (i.e. 43 degrees for 2 min)
Tumor must be unifocal & unilateral
Patients will have 6 or less extracranial sites, which can safely receive SBRT between 30 – 50 Gy in 5 fractions; a site may have multiple tumor lesions within it as long as the gross tumor volume (GTV) of the site is 8 cm or less and can be covered in an acceptable SBRT field determined by the principal investigator (PI); all gross disease must be amenable to treatment with SBRT, as allowable per normal tissue constraints; patients will not have had any prior radiation therapy significantly overlapping a tumor site to be treated
Patients will be eligible regardless of whether they have had prior nephrectomy or still have their primary tumor in-situ.
Participation in Iowa Neuroendocrine Tumor Registry
HER2-positive tumor status;
Willing to undergo the intra-tumoral (IT) injection of the poly-ICLC into the prostatic tumor as per the protocol
For disease-specific cohort participants: Must have an archival (banked) tumor sample or agree to have a new (fresh) tumor biopsy during the screening period. If a new tumor sample is needed, the disease should be accessible for a nonsignificant risk biopsy procedure (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures not extending beyond the stomach or bowel). For participants in the Western safety cohort, this biopsy is optional.
Participants with known microsatellite instability-high (MSI-H) genotype or known wild type tumor protein 53 (TP53) per local testing.
Patients with at least two liver tumor lesions with at least one with a diameter of 2 cm or bigger, which is amendable for (super-)selective TATE as the target lesion. Alternatively, patients with one intra-hepatic lesion of 2 cm or bigger and exhapetic lesion(s) are also acceptable.
Patients who are surgical or ablation candidates as determined by multidisciplinary hepatobiliary tumor conference
Subjects without baseline tumor imaging
Willingness to undergo a fresh tumor biopsy pre-treatment and on treatment, if deemed safe and feasible by treating oncologist.
Patients who are willing and able to comply with the protocol and study procedures including willingness to undergo tumor biopsy or paracentesis for tumor cells before therapy (at baseline) and after initiation of treatment (before cycle 2) for all subjects if this is clinically and safely feasible to do so
Must not have received immunotherapy, eg, tumor vaccines, within 42 days.
Subjects must have at least one target lesion in breast/chest wall/axilla which is amenable to application of high intensity focused ultrasound:\r\n* The distance from the skin: A targetable portion of the tumor must be ? 5 mm from the skin\r\n* The rib cage should not be in the prefocal ultrasound path or behind the target area of the lesion (minimum distance from the posterior aspect of the target area to rib cage must be at least 10 mm)\r\n* Subject’s tumor must be larger than 9 mm in the anterior-posterior dimension (measured by ultrasound)\r\n* Subject’s tumor must be greater than or equal to 0.3 cubic centimeters
The subject has biopsy accessible tumor and is willing to undergo biopsy prior to planned protocol treatment
Patient has a tumor in the bladder diverticulum
Histologic proof or unequivocal cytologic proof of solid tumor malignancy; this may be obtained from either the primary or any metastatic site
Evidence of active tumor lysis syndrome based on laboratory assessment
Pathologically-proven diagnosis of a solid tumor malignancy
For Arms A-F, subjects must have biopsiable disease. For Arms A, B, and C, subjects must have at least two lesions amenable to biopsy and response evaluation. For Arms D, E, and F, subjects must have at least three lesions amenable to biopsy, response evaluation, and radiation. Tumor lesions used for biopsy should not be lesions used as RECIST target lesions.
Tumor deemed accessible by metastatectomy (TIL harvest) which expects to yield > 1.5 cm^3 of resectable tumor amount
Simultaneous primary cancers or separate bilateral primary tumor sites
Patients must agree to undergo two research biopsies of (a) malignant lesion(s); the investigator must also judge that the patient has tumor(s) safely accessible for biopsy; patients may be exempt from the second biopsy if after the performance of the first biopsy it is felt that a second biopsy would be unsafe for the patient; if the patient has only one Response Evaluation Criteria in Solid Tumors (RECIST) measurable target lesion for response assessment, research biopsies must not be performed on that target lesion
The subject must have EGFR and c-Met overexpressed in tumor as determined by immunohistochemistry (IHC) test score of 2+ for both markers
The subject has tumor invading or encasing any major blood vessels
The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
The target tumor is limited to neuroblastoma; patients must have had histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines at the time of initial diagnosis
Advanced, solid tumor malignancy that is amenable to biopsy; patient must consent to 4 mandatory biopsies during study
Patients with tumor(s) invading a major vascular structure (e.g. carotid artery) or other key anatomical structure (e.g. pulmonary airway) in the event of post treatment tumor swelling and/or necrosis (hepatic and portal vein involvement allowed)
Patients with liver tumors in a location that would potentially result in significant clinical adverse effects in the opinion of investigator if post-treatment tumor swelling were to occur, including at the site of the common bile duct
Intrahepatic lesion amenable to pre and post SBRT biopsies, unless the investigator determines that the tumor biopsies would be unsafe
The subject has tumor invading or encasing any major blood vessels
The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Tumor deemed amenable to biopsy by core for metastatic site or endoscopic biopsy for primary tumor (for both before and on-treatment biopsies)
Measurable metastatic or unresectable malignancy expressing G12V mutated KRAS as assessed by one of the following methods: reverse transcriptase-polymerase chain reaction (RT-PCR) on tumor tissue, tumor deoxyribonucleic acid (DNA) sequencing or any other Clinical Laboratory Improvement Act (CLIA) certified laboratory test on resected tissue; patients shown to have tumors expressing G12V mutated NRAS and HRAS will also be eligible
Pathological diagnosis of any solid tumor histology (from any site in the body)
Pathological or clinical (i.e., by imaging) diagnosis of brain metastatic tumor lesions
Presence of inoperable tumor lesion/s from histologically confirmed solid tumors or lymphomas, in patients with at least one lesion ? 1 cm and suitable for intra-lesional injection, who have disease progression after treatment with available therapies, or who are intolerant to such treatments
Total tumor burden requiring ? 75 mL AvidinOX injection
Presence of unreachable (e.g. located in a region that cannot be reached by needle) or untreatable tumor lesions so that the benefit from the treatment of the treatable lesions does not justify patient's inclusion
Lymphoma that is amenable to safe pre-treatment and post-treatment biopsy; the safety of the procedures will be determined by the treating physician and the surgeon or other proceduralist, in consultation with the principal investigator (PI), and in accordance with standard clinical practice; acceptable sites of disease include, for example: (1) palpable tumor mass that is accessible under direct visualization or sonogram, (2) non-palpable tumor tissue that is accessible for biopsy under computed tomography (CT) or sonogram guidance, (3) bone marrow
Has at least one extracranial tumor safely treatable with radical-dose radiation therapy
The patient has a pathologic diagnosis of tumor biopsy or fine needle aspiration (FNA) of esophageal or gastric cancer of adenocarcinoma histology
Uncontrolled tumor related pain
Histologically or cytologically confirmed, primary or recurrent, head and neck squamous cell carcinoma, including variants; patients must have at least one measurable lesion in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (tumor diameter >= 1 cm; short-axis lymph node diameter >= 1.5 cm) OR by caliper measurement (tumor diameter >= 1 cm); any diagnostic pretreatment biopsy sample is acceptable including fine needle aspiration (FNA)
Participants must have disease amenable to and be willing to undergo serial core or excisional biopsies of a tumor lesion(s)
Primary tumor not amenable to TORS
Must have marker clip indicating location of target tumor in breast
Subjects must not have an MRI defined target tumor that is within 10 mm of skin (defined as volume encompassing first 3 mm from skin surface)
Subject is HLA-A*02 positive and subject's tumor shows expression of the MAGE-A4 RNA or protein.
Either the primary tumor and/or the metastatic tumor must be RB positive as defined below:\r\n* RB status: the invasive tumor must have greater than 50% of tumor cells staining positive for RB
Patients with thrombosis of the planned site of resection will not be excluded if the thrombus is caused directly by tumor burden or outflow obstruction
Pathology review demonstrates tumor cellularity no less than 30% in quantities sufficient to obtain 6-8 1 mm biopsies from the original formalin-fixed paraffin-embedded (FFPE) blocks
Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma
Evidence of tumor expression of CA19-9 based on IHC performed on tumor samples or elevated serum levels (?1.5 x ULN) of CA19-9 considered secondary to tumor
Any tumor mass greater than 10 cm in longest diameter
Patients with multiple primary lung tumors (defined below) are eligible:\r\n* Synchronous tumors (diagnosed within 6 months [mo]),\r\n** Different histology, \r\n** Same histology,\r\n** Second tumor in different lobed or lung;\r\n* Metachronous tumors (diagnosed > 6 mo apart),\r\n** Different histology,\r\n** Same histology,\r\n** Second tumor in different lobe or lung,\r\n** Tumor-free interval of at least 4 years (y)
Patients will be eligible if tumor is metastatic, unresectable, progressive, or if complete tumor resection is not considered to be feasible without substantial risk or morbidity
There will be no limit to number of prior myelosuppressive regimen for GIST or other tumor manifestations associated with NF1
Main portal vein tumor thrombus
Patients with American Joint Committee on Cancer (AJCC) (7th edition, 2010) N2-N3 nodal disease or T3-T4 primary tumor
Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors; residual measurable tumor is required for enrollment on study as outlined above
(For cohort B): Primary tumor sample collected before NACT started (on ARTEMIS) and underwent molecular testing for integral biomarkers including immunohistochemical assessment of FRalpha
Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology
Documented HER2 overexpression or gene-amplified tumor by a validated approved method
Patients are eligible if they undergo a targeted treatment recommended by the Molecular Tumor Board, excluding clinical trials
Pancreatitis that is active or within the preceding 3 months which in the judgment of the endoscopist would make tumor injection likely to trigger severe recurrent pancreatitis
Prior therapy with tumor vaccine
Patients with tumor morphology that predicts poor coverage of the majority of the tumor; this will be determined by the study chairs; patients with evidence of cystic changes greater than 1 cm in diameter will be excluded; these subjects should be discussed with the study chairs
Has a diagnosis of low grade (G1 or G2), uni- or multifocal papillary appearing bladder tumor, stage Ta.
Has or has ever had: upper tract TCC; urethral tumor (prostatic urethra included); any invasive bladder tumor known to be other than tumor Ta, low-grade (G1-G2); any evidence of lymph node or distant metastasis; any bladder tumor with histology other than TCC; or carcinoma in situ (CIS).
Has a tumor in a bladder diverticulum
For subjects with recurrent tumor, the subject had at least a 6-month cystoscopically confirmed tumor-free interval between the last tumor recurrence and screening cystoscopic examination.
Original diagnosis has been confirmed through a histopathologic review of the primary tumor slides by an expert pathologist at the Principal Investigator's institution
Subjects that do not have a baseline tumor specimen/biopsy prior to starting study medications\r\n* Tumor specimens do not need to be at Jefferson at time of eligibility determination; tumor specimens held at outside institutions should be requested for analysis of pre-treatment tumor vs post-treatment tumor
Pancreatic target tumor diameter of ? 2.0 cm (shortest axis) to ? 6.0 cm (longest axis) and a minimum tumor volume of 14.0 cc as qualified by the central reading center
The tumor must be accessible for injection
Tumor which invades the ventricular system or located in the brain stem
Prior therapy with talimogene laherparepvec, tumor vaccine
No individual tumor size is >50 mm3
Tumor is not impinging on Middle Cerebral Artery/speech-motor strip
Patients may be maintained on hormonal therapy provided there is clear evidence of tumor progression
Patient’s tumor(s) to be treated is(are) =< 5.0 cm or =< 250 cm^3
Histological confirmation of malignancy (primary tumor)
A pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2); the primary tumor location should be known or believed to be midgut
Subjects must demonstrate at least one of the following:\r\n* One or more MIBG+ and DOTATOC- tumors in addition to one or more DOTATOC+ tumors\r\n* One or more tumor sites where the calculated \safe\ radiation tumor dose is higher by at least 25% with a combination of 131I-MIBG and 90Y-DOTATOC than it is with 90Y DOTATOC alone
Tumor mitotic rate > 20/10 high-power field (hpf) and/or Ki67 index > 20% (if available)
At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis
All patients must have histologic proof of solid tumor malignancy and radiographic evidence of spine metastasis
FULL STUDY INCLUSION CRITERIA: Histological documentation of overexpressing mesothelin at the moderate (2+) or stronger (3+) level in at least 30% of tumor cells as determined by immunohistochemistry (IHC)
In the context of this clinical trial, a lesion suitable for LITT is single, enhancing, supratentorial, at least 2 cm from inner table of skull over the hemispheric convexity, and > 1 cm, but < 4 cm in cross-sectional dimension, including thalamic tumor (=< 3 cm).
Unresectable primary tumor or regional disease or distant metastases
Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
Key Inclusion Criteria:\n\n        For Phase 1\n\n          -  Patients with a locally advanced or metastatic solid tumor who:\n\n               -  have progressed on or are intolerant to standard therapy, or\n\n               -  no standard therapy exists, or in the opinion of the Investigator, are not\n                  candidates for or would be unlikely to tolerate or derive significant clinical\n                  benefit from standard therapy, or\n\n               -  decline standard therapy\n\n          -  Prior MKIs with anti-RET activity are allowed. However, prior treatment with a\n             selective RET inhibitor(s) is prohibited.\n\n          -  A RET gene alteration is not required initially. Once adequate PK exposure is\n             achieved, evidence of RET gene alteration in tumor and/or blood is required as\n             identified through molecular assays, as performed for clinical evaluation.\n\n          -  Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as\n             appropriate to tumor type.\n\n          -  Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.\n\n          -  Adequate hematologic, hepatic and renal function.\n\n          -  Life expectancy of at least 3 months.\n\n        For Phase 2\n\n        As for phase 1 with the following modifications:\n\n          -  For Cohorts 1 and 3 Subjects must have received prior standard therapy appropriate for\n             their tumor type and stage of disease, or in the opinion of the Investigator, would be\n             unlikely to tolerate or derive clinical benefit from appropriate standard of care\n             therapy.\n\n          -  Cohorts 1-4: enrollment will be restricted to patients with evidence of a RET gene\n             alteration in tumor. However, a positive germline DNA test for a RET gene mutation is\n             acceptable in the absence of tumor tissue testing for patients with MTC.\n\n          -  Cohorts 1-4: at least one measurable lesion as defined by RECIST 1.1 or RANO, as\n             appropriate to tumor type and not previously irradiated.\n\n          -  Cohort 4: radiographic PD within the previous 14 months.\n\n        Note: Patients otherwise eligible for cohort 4 who do not demonstrate radiographic PD\n        within the previous 14 months may be enrolled to cohort 5 if a compelling rationale is\n        provided by the investigator and approved by the Sponsor.\n\n        Cohort 5: (up to 50 patients):\n\n          -  Cohorts 1-4 without measurable disease;\n\n          -  MTC not meeting the requirements for Cohorts 3 or 4;\n\n          -  Other RET-altered solid tumor or other RET alteration/activation (any solid tumor,\n             excluding synonymous, frameshift, or nonsense mutations);\n\n          -  cfDNA positive for a RET gene alteration not known to be present in a tumor sample.\n\n        Key Exclusion Criteria (Phase 1 and Phase 2):\n\n          -  Phase 2 Cohorts 1-4: an additional known oncogenic driver.\n\n          -  Prior treatment with a selective RET inhibitor\n\n          -  Investigational agent or anticancer therapy within 5 half-lives or 2 weeks (whichever\n             is shorter) prior to planned start of LOXO-292. In addition, no concurrent\n             investigational anti-cancer therapy is permitted. LOXO-292 may be started within less\n             than 5 half-lives or 2 weeks of prior therapy if considered by the Investigator to be\n             safe and within the best interest of the patient, with prior Sponsor approval.\n\n          -  Major surgery (excluding placement of vascular access) within 4 weeks prior to planned\n             start of LOXO-292.\n\n          -  Radiotherapy with a limited field of radiation for palliation within 1 week of planned\n             start of LOXO-292, with the exception of patients receiving radiation to more than 30%\n             of the bone marrow or with a wide field of radiation, which must be completed at least\n             4 weeks prior to the first dose of study treatment.\n\n          -  Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of\n             starting study treatment with the exception of alopecia and Grade 2, prior\n             platinum-therapy related neuropathy.\n\n          -  Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated\n             spinal cord compression. Patients are eligible if neurologically stable and without\n             increase in steroid dose for 14 days prior to the first dose of LOXO-292 and no CNS\n             surgery or radiation has been performed for 28 days, 14 days if stereotactic\n             radiosurgery.\n\n          -  Clinically significant active cardiovascular disease or history of myocardial\n             infarction within 6 months prior to planned start of LOXO-292 or prolongation of the\n             QT interval corrected (QTcF) > 470 msec on all 3 ECGs during Screening.\n\n          -  Required treatment with certain strong CYP3A4 inhibitors or inducers.
Primary tumor excised by radical inguinal orchiectomy and pathology consistent with pure seminoma with negative surgical margins
Subjects must have measurable plexiform neurofibroma(s) amenable to volumetric MRI analysis; the target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest; tumors must be at least 3 milliliter (mL) in volume (most plexiform neurofibromas [PN] 3 cm in longest diameter will meet this criteria); if the tumor is < 3 cm in longest diameter, the patient may still be eligible; central review of the MRI of the target plexiform is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis
Patients with malignant glioma, malignant peripheral nerve sheath tumor, or other malignancy requiring treatment in the last 12 months
The subject has tumor invading or encasing any major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of XL184 (cabozantinib)
Patient must provide a tumor biopsy as the time of progression on Arm B; if a patient does not have a tumor lesion amenable of biopsy or it has been unsafe for a biopsy to be performed, cross-over will be allowed
Patients/subjects with HER2 positive tumor that have not been treated with trastuzumab prior to enrollment
Archived or newly obtained tumor material
Tumor accessible and participant consents to undergo fresh tumor biopsies.
Tumor type:
Has archive tumor tissue from primary tumor or metastatic site (excluding bone), for which the source and availability have been confirmed.
Tumor must be supratentorial only
Stereotactic biopsy will not be allowed unless there is plans for second surgery to remove >= 80% of the tumor
CELL PROCUREMENT: Subjects must not have tumor in a location where enlargement could cause airway obstruction
LYMPHODEPLETION: Subjects must not have tumor in a location where enlargement could cause airway obstruction
Patients should have microsatellite stable (MSS) tumor by polymerase chain reaction (PCR) assay or mismatch repair protein proficient (MMRP) tumor by immunohistochemistry as confirmed by the presence of MLH1, MSH2, MSH6, and PMS2; the diagnosis of colorectal cancer should be confirmed by pathology either on the primary tumor or from a prior biopsy of a metastatic disease site
No more than 42 days should elapse from the day study-specific tumor sample is taken at initial diagnosis (or subsequent procedure) to the time of the first intake of ODM-201.
Subject that underwent excisional biopsy of the primary tumor.
Direct tumor extension into the stomach, duodenum, small bowel or large bowel
At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis
Patient must consent to two mandatory biopsies and have tumor amenable to biopsy
Willing to undergo tumor biopsy at baseline and during treatment (during week 6 or 7); please note that tumor biopsy is not needed in subjects where the tumor is not accessible or if tumor biopsy is considered not in patient’s best interest
Is medically able and willing to undergo needle biopsy of a tumor lesion; PD-L1 expression is not required to enroll in the trial
Oligometastatic disease or unresectable primary abdominal malignancy with biopsy-proven primary disease histology of solid tumor categorization; patients with a diagnosis of hepatocellular carcinoma do not require a biopsy
Patients must have recurrent disease, histologically proven or imaging suggestive of recurrent disease as determined by principal investigator (PI); prior implantation of Gliadel wafers is acceptable, if tumor recurrence is confirmed by histologic examination of the recurrent tumor
Patients must agree to enroll on the Neuro-Oncology Branch (NOB) Natural History protocol to allow the assessment of molecular tumor markers
Willingness to undergo core biopsy of primary hepatic tumor prior at baseline and again at cycle 2 day 1
Tumor size at least 5 mm with planned primary surgery at Mount Sinai
Tumor size less than 5 mm
Pathologic confirmation of solid tumor, including central nervous system tumor or lymphoma, or leukemia
Tumor size at least 2 cm in one dimension by clinical or radiographic exam (World Health Organization [WHO] criteria); patients with histologically confirmed palpable lymph nodes may be enrolled regardless of breast tumor size
Subjects who have undergone at least six months of chemotherapy without radiologic progression of the tumor burden
Willingness to provide consent for biopsy samples; tumor biopsies will be required for all subjects, tumor lesions used for biopsy should not be lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy; if a RECIST target lesion is used for biopsy the lesion must be >= 2 cm in longest diameter
An inadequate tumor specimen as defined by the local pathologist
ACTolog target expression as evaluated by the in vitro diagnostic device IMA_Detect: Patient's tumor must express at least one ACTolog target as assessed by quantitative PCR (qPCR) (to be assessed from a tumor biopsy to be performed if all other eligibility criteria are met).
Diagnosis of localized breast, uterine or cervical cancer that is either biopsy proven or suspected based on history, physical, and/or radiographic findings, and who are planned for definitive resection of the tumor without the use of neoadjuvant chemotherapy or radiation therapy at Thomas Jefferson University Hospital (TJUH) are eligible to participate
Subjects that do not have a baseline tumor specimen/biopsy prior to starting study medications\r\n* Tumor specimens do not need to be at Jefferson at time of eligibility determination; tumor specimens held at outside institutions are not a reason for exclusion; samples from outside institutions should be requested for analysis of pre-treatment tumor versus (vs) post-treatment tumor
Pancreatic tumor size =< 5 cm
Inaccessible tumor or lack of consent for sequential biopsies
The tumor must be supratentorial
Patients must have a histologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; additionally, in the opinion of the investigator the primary site of the metastatic or unresectable tumor must have arisen within a previously irradiated site and be considered a radiation-induced tumor
Patients must have a bone marrow biopsy available, or one scheduled to be performed for a clinical indication so that survivin expression could be determined (note: survivin staining in tumor need not be resulted prior to enrollment or treatment as it is obtained for correlative science)
At least 4 weeks must have elapsed since receiving medical therapy directed at NF1 related tumor manifestations
May not have a NF1 related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy, radiation, or surgery
Willing to provide tumor tissue amenable to ultrasound or computed tomography (CT)-guided biopsy for biomarker analyses\r\n* Patients with malignant ascites are permitted to participate and provide ascites samples for biomarker analyses\r\n* Patents receiving radiation to a single metastatic site in which only the primary tumor is accessible for biopsy by endoscopy will also be eligible
Patients must have multiple tumor lesions (at least 2): one for the ablation procedure and another for evaluation located outside the proposal ablation zone
Primary tumor >= 3 cm (for all stages entered) to increase the likelihood that excess tumor will be available after resection
Primary tumor of the nasopharynx (nasopharyngeal carcinoma)
Able and willing to give valid written consent for available archival tumor samples or fresh tumor biopsies/resections
Histologically confirmed solid tumor malignancy for which no curative therapy exists with at least 25% of tumor cells expressing mesothelin as determined by NCI Laboratory of Pathology; determination can be made using archival tumor tissue or fresh biopsy; subjects with epithelioid mesothelioma and pancreatic adenocarcinoma are automatically eligible and are not required to have this test
Low tumor burden according to GELF criteria defined as:
Based on clinical and radiographic evidence the tumor needs to be deemed resectable preoperatively by the surgeon and when necessary (determined by the surgeon) tumor board review
Patients deemed to have un-resectable disease by the treating surgeon or upon tumor board review
Patients with unresectable tumor
Histologic or cytologic confirmation of advanced solid tumor.
Tumor amenable to biopsy will be mandatory for this study
PK/PD/biomarker/metabolite expansion cohort(s) only: Subjects must consent to pre- and post-dose tumor biopsies and additional sample collection procedures.
Tumor size > 4cm in largest dimension
Resectable primary tumor of the head, body or tail of the pancreas defined per National Comprehensive Cancer Network (NCCN) guidelines version 2.2015:\r\n* No extra-pancreatic disease, aside from lymphadenopathy\r\n* No arterial tumor contact (celiac axis, superior mesenteric artery, or common hepatic artery)\r\n* No tumor contact with the superior mesenteric vein or portal vein or =< 180 degree contact without vein contour irregularity
Radio-opaque markers must be present within the tumor bed; in patients who have undergone surgical resection, radio-opaque surgical clips within the tumor bed can be used as fiducials; patients without surgical clips in the tumor bed must be able to have fiducials placed endoscopically, laparoscopically, or through a computed tomography (CT)- or ultrasound-guided technique; if not, the tumor must be posterior and adjacent to the aorta, and treatment will only be permitted at the discretion of the principal investigator
Patients with evidence of gross tumor invasion into the lumen of the stomach or small bowel are not eligible; if imaging suggests luminal invasion of tumor, this must be ruled out endoscopically before the patient can be enrolled on study
Patients must be untreated with curative-intent surgery for current diagnosis of stage III, IVa, or IVb disease; diagnostic biopsy of primary tumor and/or nodal sites is permitted\r\n* Diagnostic simple tonsillectomy is permitted, provided patient has Response Evaluation Criteria in Solid Tumors (RECIST)-measurable nodal disease\r\n* Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy), and has not recurred
A minimum tissue requirement of >= 3 core biopsies with tumor involvement and at least 50% tumor involvement in one of the core biopsies is required
Central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (i.e. carotid artery)
Paired, pre- and post-treatment, tumor biopsy is optional for subjects enrolled in the Dose Escalation and Food-effect cohorts
Paired tumor biopsy is mandatory for all subjects enrolled in the Expanded cohort; subjects should agree to and be eligible for paired tumor biopsy
Untreated and uncontrolled second tumor in the past 2 years
Relapsed, refractory, or recurrent malignancy; all solid tumor diagnoses will be eligible
Well-circumscribed, measurable intraparenchymal brain lesion(s) with maximum tumor diameter =< 3.0 cm; if multiple lesions are present, the other(s) must not exceed 3.0 cm in maximum diameter; at least one lesion must be >= 0.5 cm in maximum diameter to be considered measurable disease
The primary tumor in the colon or rectum may be intact or resected
Tumor characteristics - any of the following are excluded:\r\n* Evidence of distant metastases\r\n* Tumors whose location is restricted to the tubular esophagus (i.e., without involvement of the GEJ or cardia)\r\n* Tumors whose proximal end are at the level of the carina or higher\r\n* Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula\r\n* Palpable supraclavicular nodes, biopsy-proven involvement of supraclavicular nodes, or radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension)\r\n* T1N0M0, T4Nany, or in situ carcinoma\r\n* Tumor must not extend 5 or more cm into the stomach
Dose Expansion Cohort Group 1 and 2: At least one tumor lesion amenable to repeat core needle biopsy or punch biopsy without unacceptable risk of a major procedural complication
Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology
Documentation of CD19 expression on any prior or current tumor biopsy
Evidence of ROR1 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen
Low tumor burden with at least one lesion that is suitable for image-guided intratumoral injection and needle biopsy.
Allergy to lidocaine, fentanyl, midazolam, or propofol (may be used during tumor biopsy or injection)
PRIOR TO CELL PROCUREMENT: Tumor in a location where enlargement could cause airway obstruction
PRIOR TO LYMPHODEPLETION: Tumor in a location where enlargement could cause airway obstruction
PRIOR TO INFUSION OF ATLCAR.CD30 CELLS: Tumor in a location where enlargement could cause airway obstruction
Surgical treatment of the breast with lumpectomy plus (+) clinical target volume (CTV) margin up to 65 cc's or 5 cm in maximum dimension with histologically confirmed margins free of tumor (negative margins defined as no tumor on ink in all directions); re-excision of surgical margins is permitted
Gross disease within the breast must be unifocal; (patients with microscopic multifocality are eligible as long as the total extent of tumor, gross and microscopic, occupies a volume with greatest dimension 3 cm or less)
Pathologically confirmed advanced solid tumor cancers
The presence of the target antigen, EGFRvIII, must be identified on tumor tissue by immunohistochemistry (IHC) or polymerase chain reaction (PCR)
Unequivocal evidence of tumor progression during prior bevacizumab treatment per RANO criteria.
Tumor located entirely in the infratentorium.
PHASE II DOSE EXPANSION IN NEWLY DIAGNOSED GBM: Patients must have completed standard radiation therapy with concurrent temozolomide (TMZ) within 5 (weeks) wks of enrollment and must not have evidence of progressive disease on post treatment imaging; progression can only be defined using diagnostic imaging if there is new enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line) or if there is unequivocal evidence of viable tumor on histopathologic sampling(e.g., solid tumor areas [i.e,> 70% tumor cell nuclei in areas], high or progressive increase in mindbomb homolog 1[MIB-1] proliferation index compared with prior biopsy, or evidence for histologic progression or increased anaplasia in tumor); Note: given the difficulty of differentiating true progression from pseudoprogression, clinical decline alone, in the absence of radiographic or histologic confirmation of progression, will not be sufficient for definition of progressive disease in the first 12 weeks after completion of concurrent chemoradiotherapy
Patient must be willing to consent to MSKCC protocol 12-245 (“Tumor Genomic Profiling in Patients Evaluated for Targeted Cancer Therapy”)
Evidence of > 1 area of CIS not associated with papillary tumor at this time
Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor
Patients must be able to have fiducials placed; if not, the tumor must be posterior and adjacent to the aorta and treatment will only be permitted at the discretion of the principal investigator
Presence of duodenal or gastric invasion by the tumor as noted by esophagogastroduodenoscopy (EGD) at time of fiducial placement
Tumor =< 12 cm from anal verge as determined by MRI or endoscopy
No clinically detectable (MR, endoscopy or digital rectal examination [DRE]) tumor present
Treatment plan must include primary site biopsy followed by resection of the primary tumor site and any metastatic sites at time of surgery
Patients with del(17p) by FISH (or known tumor protein p53 [TP53] mutation)
There is no specific tumor size cut-off for this protocol; however, the radiation treatment plan must meet the protocol’s dose constraints
Tumor size must be >= 2 cm in the longest dimension
For biopsy identified patients: be willing to undergo repeat biopsy of a tumor lesion before treatment and after radiation; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the principal investigator\r\n* Note: enforcement of biopsy requirement may come into effect for all patients depending on the state of accrual compared with number of obtained biopsies at any point in the study
An archival tumor specimen or newly obtained tumor sample may be submitted at screening/baseline (a fresh tumor sample is preferred), unless agreed differently between Novartis and the Investigator.
No evidence of disease progression: defined as increase in tumor size of > 25% or new lesions
If a primary tumor is in place, it must be asymptomatic
JUST PRIOR TO FIRST VACCINATION (WITHIN 21 DAYS): patients must have either measurable disease per Response Criteria in Solid Tumors (RECIST) version (v)1.1 or evaluable disease defined as an elevated tumor biomarker (CA19-9, carcinoembryonic antigen [CEA] or circulating free deoxyribonucleic acid [cfDNA] mutation); pancreatic cancer patients with an elevated tumor marker following a primary pancreatic surgery would be eligible
Evidence of MCPyV TAg tumor expression by immunohistochemistry on any prior or current tumor specimen or viral oncoprotein antibody confirmation within 6 weeks of the start of study intervention
Subjects must be willing to undergo malignancy genotyping for tumor protein 53 (TP53) mutation, insertion, or deletion at screening
Patient has a tumor amenable to injection of Toca 511 (ie, ? 2 cm and not close to or invading major vessels).
Patients acceptance to have a tumor biopsy
Need for urgent or emergent nephrectomy to relieve symptoms relating to the primary tumor
At least one tumor must qualify to be an index lesion for modified WHO criteria.
Tumor may not extend greater than 4 cm below the gastroesophageal junction
Unequivocal metastatic tumor at baseline
Contrast-enhancing tumor component crossing the midline, multi-focal tumor, or tumor dissemination (subependymal or leptomeningeal)
cPoP study: any tumor with at least 2 (sub)cutaneous tumor/metastases at least 2 cm apart which are RT naïve with an indication for high dose palliative RT
Willing to have tumor biopsies collected in cPoP
Tumor PD-L1 status, with Immunohistochemical (IHC) assay confirmed by a reference laboratory, must be known prior to randomization.
Patients must have an extra-cranial primary tumor diagnosis
Adjacent tumor location to optic apparatus or brainstem, precluding achievement of meaningful dose with SRS
Primary brain tumor
A single liver lesion with tumor size >= 3 cm
Maximum tumor size of 7 cm
Tumor for which adequate radiation dosage cannot be safely delivered
Ability to have a skin and tumor biopsy from any site; patients without accessible tumor for biopsy will be considered on a case by case basis\r\n* Patients who cannot be biopsied will not be replaced (although up to 5 ineligible/inevaluable patients can be replaced)\r\n* Patients without accessible tumor for biopsy must provide archived tumor from the most recent biopsy available
The subject has a primary brain tumor
The subject has tumor in contact with, invading or encasing any major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Consent to provide archived tumor biopsy material (all patients)
Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy / Transurethral Resection of Bladder Tumor (TURBT) to starting study treatment
Tumor that is accessible for mandatory biopsy
Approximately 1 mg (1 cm3) of accessible and dispensable tumor that will not interfere with pathologic staging
Insufficient tumor available to produce vaccine
Subject must have advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit but based on evidence gathered in this study or from external sources, the Sponsor in consultation with the Investigators, may decide to limit to specific tumor types.
Availability of an existing tumor biopsy sample (and consent to allow pre-treatment tumor biopsy)
Participants must be eligible to undergo laparoscopic or robotic low anterior resection with or without a temporary diverting stoma, based on multidisciplinary tumor board consensus
Must undergo a new tumor biopsy for acquisition of resistant tumor tissue; subjects unable to undergo a new tumor biopsy are not eligible for Part B
Must have at least 1 liver lesion amenable to SBRT with tumor size < 15 cm (single lesion or sum); up to 3 lesions will be irradiated
Surgical Stage III disease includes those patients with positive adnexa, parametrial involvement, tumor invading the serosa, positive pelvic and/or para-aortic nodes, or vaginal involvement.
Patients with residual tumor after surgery (any single site) exceeding 1 cm in maximum dimension.
Patient’s carcinoma must express the mucin 16 (MUC16) ectodomain (ecto) antigen detectable by immunohistochemistry (IHC) analysis of banked (paraffin embedded) or freshly biopsied tumor
Subjects with tumor amenable to potentially curative therapy
Patients must have recurrent or persistent EOC (epithelial ovarian, fallopian tube or primary peritoneal carcinoma); histologic documentation of the original primary tumor is required via the pathology report
Patients must not have tumor in a location where enlargement could cause airway obstruction
cTis-T3 cancer judged to benefit (by treating radiation oncologist) from a tumor bed boost
Histologically documented diagnosis of solid tumor
Patients must have CDKN2A-deficient tumor (deletion or mutation); definition of CDKN2A deficient tumor:\r\n* CDKN2A deletion or mutation by any Clinical Laboratory Improvement Amendments (CLIA)-certified sequencing OR\r\n* >= 30% of tumor cells with (at least) hemizygous deletion by fluorescent in situ hybridization (FISH); status will be determined from archived tissue
Subjects with any tumor type (except lung) for which carboplatin plus paclitaxel chemotherapy would be appropriate • Paclitaxel Arm:
Subjects with any tumor type (except lung) for which paclitaxel chemotherapy would be appropriate • Anastrozole Arm:
Radiographic evidence of renal cancer with IVC tumor thrombus
Tumor thrombus must be >= level II
Patient eligible for SABR to the IVC tumor thrombus as decided by the treating radiation oncologist
Patient eligible for IVC tumor thrombectomy as decided by the treating urologist
Subjects who have had radiotherapy to a target within 3 cm of the IVC tumor thrombus
Based on clinical and radiographic evidence the tumor needs to be deemed resectable preoperatively
Unresectable tumor
Androgen receptor positivity, defined as >= 10% of tumor cell nuclei with immunoreactivity for AR on central review at Vanderbilt
Primary tumor sample collected before NACT started and
Primary tumor may be located anywhere in the pancreas
The patient must be able to have fiducial markers implanted into the pancreatic tumor, and receive radiation regimen as specified in the protocol
Subject for whom tumor lysate does not meet release criteria
Patient’s acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator)
Have a newly diagnosed, biopsy-proven adenocarcinoma of the head, neck and uncinate of the pancreas, and is a candidate for a pancreaticoduodenectomy; if the biopsy is not sufficient for diagnosis, the patient can be considered to meet eligibility if the study team agrees that clinically the patient’s tumor is suspected to be adenocarcinoma
AT THE TIME OF PROCUREMENT: Subjects having a tumor resection
Patients must have peritoneal recurrence of epithelial adenocarcinoma or carcinosarcoma of ovarian, tubal, or peritoneal origin; histologic documentation of the original primary tumor is required via the pathology report; original tumor blocks from primary diagnosis will be reviewed by our study pathologist at Magee
Patients must have documented available tumor greater than 1 cm of bulk tumor mass or 200 cc of ascites fluid for tumor isolation prior to starting chemotherapy
Cohort 1: Any solid malignant tumor.
Patients with newly diagnosed or progressive DIPG as confirmed by gadolinium enhanced magnetic resonance imaging (MRI) are eligible; MRI must demonstrate that at least 2/3 of the tumor is situated in the pons and that the origin of the tumor is clearly in the pons; biopsy is not required; tumors with features not typical of diffuse intrinsic brainstem glioma are not eligible; these include dorsally exophytic brainstem gliomas, cervicomedullary junction tumors, and focal low grade gliomas of the midbrain or brainstem which should undergo resection and pathologic evaluation; patients, who have received re-irradiation for progression of the tumor, will be eligible if they show evidence of measurable progressive disease after the re-irradiation; patients at diagnosis with involvement of the spine will not be eligible, however if at progression features of spine involvement are present they will be eligible for stratum II
At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
Able, willing to give written consent for available archival tumor samples (not mandatory) and tumor biopsies before and during protocol therapy (mandatory).
An HRD score >= 42 on the Myriad HRD Assay as assessed on a metastatic tumor biopsy sample; in the case that an adequate metastatic tumor tissue biopsy is not feasible, we will assess the HRD score from the primary breast tumor
Uncontrolled tumor related pain
The subject must agree to undergo the pre- and post-treatment research biopsies if a non-osseous metastatic site is available for biopsy; the pre-treatment biopsy will be standard of care, and used for diagnostic purposes to assess ER/ progesterone receptor (PgR) / HER2 status and confirm the presence of breast tumor cells; the post-treatment (day 11) biopsy will be performed for research purposes; both the pre- and post-treatment biopsies will be assessed on-site by a pathologist by touch-prep to ensure that the biopsied tissue contains tumor cells
There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per Response Assessment in Neuro-Oncology (RANO) criteria; when the interval is less than 12 weeks from the completion of radiotherapy, the use of positron emission tomography (PET) scan is allowed to differentiate between evidence of tumor recurrence and pseudoprogression
Patients already enrolled to the separate Tumor Genomic Analysis and Molecular Testing for Personalized Cancer Therapy study, for which a personalized therapeutic plan has been successfully created under that protocol and selected by the multidisciplinary tumor board of experts (MTBE) for use in this therapeutic clinical trial
Willingness to donate blood for biomarker studies related to the type of therapies used in this trial and the tumor types being treated
At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
Patients with any tumor obstructing the distal bile duct and causing an indwelling biliary SEMS occlusion
Patient will have a tumor suitable for fine needle aspirates (FNA) or core biopsy for research purposes (2 or more FNAs if core is not feasible)
Preoperative proctoscopy confirming tumor extent as no less than 5 cm and no greater than 12 cm from the anal verge
Clinical T4 tumor
Tumor-induced symptomatic bowel obstruction
Submission of tumor samples from the diagnostic biopsy and breast surgery is required for all patients
Following biopsy, prior to administration of D2C7-IT, the presence of recurrent tumor must be confirmed by histopathological analysis
Patients with contrast-enhancing tumor component crossing the midline, actively growing multi-focal tumor, infratentorial tumor or tumor dissemination (subependymal or leptomeningeal)
Tumor invading or encasing any major blood vessels
Evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Patients in the dose expansion part must have tumor that is amenable for biopsy
Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or undifferentiated thyroid cancer that demonstrates mutation in the ALK gene as assessed by sequencing of the tumor specimen for Arm A; other ALK abnormalities as detected by the approved fluorescence in situ hybridization (FISH) test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana immunohistochemistry (IHC) test will also be seen as evidence of ALK abnormality and meeting eligibility requirement
Metastatic disease is allowed if investigator feels liver directed therapy could offer palliative benefit (i.e., minimal extrahepatic tumor burden)
Bilirubin < 2.0 mg/dL unless secondary to bile duct blockage by tumor
Patients with gastrointestinal stromal tumor (GIST)
Patients must have a measurable primary tumor (undetectable NSCLC primary tumor is ineligible)
Presence of nodules considered neoplastic in the same lobe or other ipsilateral lobe as the primary tumor (stage T3-4), unless the nodule can be encompassed in the stereotactic boost (gross tumor volume [GTV]boost) without exceeding a total GTVboost size of 10 cm as defined by the sum of the largest CT axial dimensions of each nodule
< 90% solid component of tumor on screening cross-sectional imaging
Pre-existing tumor-infiltrating lymphocytes in an archived tumor specimen or fresh biopsy, defined as an average of >= 4 TILs/high power field (HPF) in 5 consecutive HPFs, within the area with the highest TILs at low power; or, DNA mismatch repair deficiency, determined by immunohistochemistry or polymerase chain reaction per Memorial Sloan-Kettering Cancer Center (MSKCC) institutional standard practice; DNA mismatch repair deficient tumors may be TIL positive or negative
Measurable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria,\r\n* Must be amenable to ultrasound or computed tomography (CT)-guided biopsy of one metastatic lesion\r\n* Peritoneal disease as the sole site of occult metastasis or presenting as malignant ascites is acceptable if a cell block of tumor cells can be obtained showing > 20% viable tumor cells
City of Hope (COH) Clinical Pathology confirms IL13R alpha 2+ tumor expression by immunohistochemistry (>= 20%, 1+)
Confirmation that primary tumor expresses mammaglobin-A by IHC
Tumor proliferation-related Ki-67 antigen (Ki67) value is reported as “low” after 14 days of endocrine therapy
Primary site of tumor of oral cavity, nasopharynx, sinuses, or salivary glands
Patients with sub-optimal resection (any single tumor larger than 1 cm)
Recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma; histologic confirmation of the original primary tumor is required
IDH1^R132H expression in primary tumor
Imaging studies show evidence of recurrent tumor(s); if a patient is going to be enrolled to dose level two or higher, the patient must have a component of supratentorial disease (so as to enable placement of a Rickham reservoir/catheter) that is amenable to resection or biopsy
Participant must be in need of a craniotomy for tumor resection or a stereotactic brain biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy
Based on the neurosurgeon’s judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
Tumor size > 7 cm in one direction
Patients must agree to undergo two separate biopsies of a malignant lesion; biopsies do not need to be done if one of the following apply:\r\n* If either the site investigator or person performing the biopsy judges that no tumor is accessible for biopsy or that biopsy poses too great of a risk to the patient (if the only tumor accessible for biopsy is also the only lesion that can be used for RECIST v1.1 response evaluation, then the patient may be exempt from biopsy after discussion with the MSK principal investigator)\r\n* The goal will be to have a minimum of 6 patients from Cohort A and 3 patients from Cohort B attempt to have one or both of these research biopsies done (for a total of 9 patients total); accrual may be limited only to subjects for whom tumor is accessible for biopsy and attempt at biopsy is considered safe if continued enrollment of those who are not candidates for biopsy make it impossible to reach the accrual goals for research biopsies described above (e.g., if 19 [of 25] patients are accrued to Cohort A without any biopsies having been obtained within the cohort, then all further subjects who are registered to that cohort must qualify for attempted research biopsy in order to be enrolled into the study [i.e., subjects who would have been excluded from having biopsies done due to the above reasons would be excluded from participating in the study; these conditions also apply to Cohort B])
Patient amenable to liver tumor biopsy
Patients must be deemed able to undergo optimal cytoreductive surgery (CRS) defined as cytoreduction (CC)-score of 0 or 1 based on imaging\r\n* Cytoreduction is defined as the burden of residual disease nodules left at the end of surgery (CC-0: no visible disease; CC-1: residual tumor nodules =< 2.5 mm in size; CC-2: residual tumor nodules 2.5 mm-2.5 cm in size; CC-3: residual tumor nodules > 2.5 cm in size)
Tumor not suitable for resection at the time of study entry; (transplant eligible patients are allowed)
Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
T4 tumor
Submit an evaluable tumor sample for analysis.
The subject has tumor abutting, invading or encasing any major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Tumor size at least 2 cm in one dimension by clinical or radiographic exam (World Health Organization [WHO] criteria); patients with palpable lymph nodes may be enrolled regardless of tumor size
Documented recurrent disease: recurrent disease is defined either as radiological confirmation of the tumor, as an increase in tumor size of at least 25% based upon serial magnetic resonance (MR) images, or as development of a new site of disease\r\n* Tumor volume will be calculated using the sum of the largest cross-sectional perpendicular diameters of contrast-enhancing tumor, the sum of the largest cross-sectional perpendicular diameters of fluid attenuated inversion recovery (FLAIR) abnormality, or as worsened spectroscopic characteristics for any tumor type (development of >= 2 new voxels with choline to N-acetyl aspartate index [CNI] >= 3, or >= 25% increase in the sum of the CNI ratios within a group of previously abnormal voxels [where abnormal is defined as CNI ? 3])\r\n* Disease must be evaluable, but does not need to be measurable\r\n* The target site for SRS does not need to be located in a previously-irradiated area
Have portal or hepatic vein tumor invasion/thrombosis.
Less than 6 months from the date that local treatment (surgical or radiation) of the primary tumor was finalized
Patients must have an extra-cranial primary tumor diagnosis
Primary brain tumor
patients with a history of malignant tumor who have been disease free for at least five years and are not currently being treated.
An archived tumor specimen is available for collection
The subject has a primary brain tumor
The subject has tumor in contact with, invading or encasing any major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Patient’s tumor must have documentation of the presence of an IDH-1 and/or IDH-2 mutation of any type
Recurrent tumor must be a solid, single, supratentorial, contrast-enhancing HGG which have a tumor diameter no larger than 4 cm or volume of 34 cm^3
Contrast-enhancing tumor which crosses the midline
Nonparenchymal tumor dissemination (e.g., subependymal or leptomeningeal)
The patient's tumor is HPV positive by polymerase chain reaction (PCR) or in situ hybridization (ISH) assay of tumor biopsy
Patients with tumor-caused symptomatic bowel obstruction
Maximum tumor size ?1.5 cm in its greatest diameter
Tumor with ?25% IDC components
Infratentorial, leptomeningeal, or multifocal tumor
Single tumor less than 5 cm
A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective cohort
Tumor located in the brainstem
At least one (usually up to 3) gold fiducial placed in or around tumor, can be performed on the same day-after signing research informed consent
The tumor lesion is 5-15 cm from anal verge
Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology
No prior therapy, unless an emergency situation requires local tumor treatment (discuss with principal investigator [PI])
CD19-positive tumor
Tumor in a location where enlargement could cause airway obstruction
Gross disease must be unifocal with pathologic (invasive and/or ductal carcinoma in situ [DCIS]) tumor size 3 cm or less; (patients with microscopic multifocality are eligible as long as total pathological size is 3 cm or less)
Multifocal primary tumor
The primary tumor involves true vocal cord(s) (glottis) or arytenoid(s)
Patient must be able to have fiducials placed; if not, the tumor must be posterior and adjacent to the aorta and treatment will only be permitted at the discretion of the principal investigator
For tumors that are invasive, if in the presence of extensive intraductal component (EIC), the entire pathologic tumor size (including both the intraductal and invasive component) must be 3.0 cm or less.
Must not have an advanced malignant hepatic tumor
Documented expression of CD30 on tumor cells
Must be willing and able to accept at least two tumor biopsies
Presence of a prolactinoma (prolactin-releasing pituitary tumor)
Patients must undergo pre-treatment direct laryngoscopy (DL) endoscopic tumor staging and CT scanning
Patients must be willing to undergo 2 tumor biopsies
A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)
Patients whose tumor is not accessible for a core biopsy
EBV positive tumor (can be pending)
EBV positive tumor
Patients in the tumor-specific endometrial carcinoma expansion cohort that have known mutation must be willing to provide consent for biopsies
The targeted tumor tissue is located in the cerebral hemispheres, > 2.5 cm from the inner table of the skull. Non-targeted parts of the tumor may extend outside the treated tumor limits.
Size of the targeted portion of the tumor (i.e. prescribed ROT) is less than 2.5 cm in diameter (8 cm3 in volume). The non-targeted tumor tissue may exceed the targeted volume.
The tumor's not visible on the pre-therapy imaging
The tumor presenting the following imaging characteristics
The sonication pathway to the tumor involves
The most recent brain tumor pathology obtained for the patient must be glioblastoma or anaplastic astrocytoma
Patients must have either (1) a diagnosis of NB as defined by international criteria i.e., histopathology (confirmed by the Memorial Sloan-Kettering Cancer Center [MSKCC] Department of Pathology) or bone marrow (BM) metastases plus high urine catecholamine levels, or (2) a tumor that is GD2-positive by immunostaining with m3F8\r\n* A non-NB tumor is defined as GD2-positive by immunostaining with m3F8; if fresh or frozen tumor is not available for immunostaining, patients will be considered eligible if published reports show that > 50% of that tumor type is GD2-positive by immunohistochemistry; (Note: tissues must be fresh/frozen as fixed, paraffin-embedded specimens are unsuitable for anti-GD2 immunostaining); tumors known to be GD2-positive by this criteria do not need immunostaining; these include: melanoma (> 50%), desmoplastic small round cell tumors (70%), osteosarcoma (88%) and soft tissue sarcomas including liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma (93%)
Uncontrolled tumor in the brain
Have metastatic and/or unresectable pathologically confirmed well-differentiated, typical or atypical neuroendocrine tumor of the lung
Willingness to undergo a pre-treatment and on-treatment tumor biopsy to obtain the specimen.
tumor that carries a missense HRAS mutation
Subject consents to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status
Participants for whom chemotherapy or intraoperative or post-operative radiation therapy is planned as part of the overall primary tumor treatment
Patients with primary tumor histology of lymphoma, leukemia, or germ cell tumor
ICGCT including pure germinoma and MMGCT; patients with histologically proven germinoma and MMGCT, including endodermal sinus tumor (yolk sac tumor), embryonal carcinoma, choriocarcinoma and mixed germ cell tumor will be eligible for the study; patients with mature/immature teratoma who have tumor marker elevations are eligible on this study; patient with ONLY mature and/or immature teratoma are ineligible in the absence of the tumor marker elevations
Patients with NO elevation of serum and/or CSF HCGB and AFP MUST have histological diagnosis of malignant germ cell tumor (GCT) or germinoma
Patients with the diagnosis of mature or immature teratoma in the absence of tumor marker elevations are excluded from the study
Gross disease must be unifocal with pathologic (invasive and/or DCIS) tumor size 3 cm or less; (patients with microscopic multifocality are eligible as long as total pathologic tumor size is 3 cm or less)
CD30 positive tumor (can be pending at this time)
CD30 positive tumor
Tumor in a location where enlargement could cause airway obstruction
Tumor type demonstrated on imaging to be infiltrative, tumor volume > 70% of the target liver volume, or tumor nodules too numerous to count, or tumor volume > 50% combined with an albumin < 3 g/dL, or complete occlusion of the main portal vein.
Patients with histologically confirmed, non-central nervous system (CNS) solid malignancies who have been previously radiated and have a tumor recurrence in or near prior radiation fields; re-biopsy of the recurrence is not required and left to the discretion of the treating physician, although every effort should be made to confirm recurrence
WHO grade II: any tumor, either completely or incompletely excised; any recurrent tumor
WHO grade III and hemangiopericytoma: any tumor, either completely or incompletely excised; any recurrent tumor
Patients must have the diagnosis of (a) DSRCT with peritoneal involvement or (b) other 8H9-positive solid tumors involving the peritoneum (e.g. adrenocortical carcinoma, Wilm's tumor)
The tumor has been excised with a breast-conserving resection and there is no tumor seen at any of the margins of the resection
Detectable tumor prior to mobilization regimen
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
Previous vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine
Growing teratoma syndrome, defined as enlarging tumor masses with normal serum markers during chemotherapy for nonseminomatous GCT
Subjects must have had histologic verification by a pathologist of cancer at original diagnosis; the tumor must be a non-CNS solid tumor; for subjects to be enrolled on the intratumoral arm, at least one lesion must be amenable to HSV1716 injection without undue risk, as determined by the interventional radiologist; disease must be considered refractory to conventional therapy or for which no conventional therapy exists
The tumor volume must be a minimum of three times the injection volume; in the first and second dose levels, the lesion to be injected must be at least 18 mm in each of 3 dimensions as determined by computed tomography (CT) or magnetic resonance imaging (MRI) scans; lesions not meeting this requirement may be used if volumetric measurements show it to be >= 3 mL; in the third dose level, the lesion(s) to be injected must meet minimal tumor measurements and volume for each 1 mL fractionation of the injection volume (5mL); a single lesion meeting this requirement may be injected or the total volume may be distributed in up to 3 lesions meeting measurement and volume requirements as follows:\r\n* 5 mL of HSV1716; 30 mm minimum tumor length in each dimension; 15 mL minimum tumor volume\r\n* 4 mL of HSV1716; 28 mm minimum tumor length in each dimension; 12 mL minimum tumor volume\r\n* 3 mL of HSV1716; 26 mm minimum tumor length in each dimension; 9 mL minimum tumor volume\r\n* 2 mL of HSV1716; 23 mm minimum tumor length in each dimension; 6 mL minimum tumor volume\r\n* 1 mL of HSV1716; 18 mm minimum tumor length in each dimension; 3 mL minimum tumor volume\r\n** Thus, the full 5 mL may be injected into a >= 15 mL tumor; 2 mL each may be injected into two >= 6 mL tumors plus 1 mL into a >= 3 mL, tumor, etc.; if a patient has multiple lesions but these criteria for injection cannot be met, they may be considered for the intravenous arm
Patients with skin involvement, regardless of tumor size
Confirmed diagnosis of metastatic intrahepatic carcinoma; the histopathology confirmation criterion may be waived in patients with a radiographically identifiable liver mass, known laboratory or clinical risk factors for cancer or elevated tumor markers such as AFP
Patient has a radiologically and /or pathologically confirmed diagnosis of a renal tumor
Patients must have a histologically confirmed diagnosis of a malignancy known to be 8H9 reactive; 8H9 expression must be confirmed by immunohistochemical staining of tumor and assessed by the Department of Pathology or by immunofluorescence of bone marrow except for patients confirmed to have neuroblastoma or an embryonal tumor (such as medulloblastoma, retinoblastoma, rhabdomyosarcoma and desmoplastic small round cell tumor [DSRCT])
Patients must have central nervous system (CNS)/ leptomeningeal disease which is refractory to conventional therapies or for which no conventional therapy exists OR recurrent brain tumors with a predilection for leptomeningeal dissemination (primitive neuroectodermal tumor [PNET], rhabdoid tumor)
Must be willing to release tumor biopsy specimen used for diagnosis of metastatic NSCLC (if available) for additional exploratory tumor molecular profiling.
Must be willing to provide a tumor biopsy specimen 9 weeks after the start of treatment for exploratory analyses, if considered safe by the Investigator.
Subject's tumor expresses CLDN18.2 in ? 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
Apparent tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator
Patient must have confirmed HER2 overexpression or gene-amplified tumor
Tumor thrombus involving main trunk of portal vein or inferior vena cava
High FGFR1 or 3 mRNA (Messenger ribonucleic acid) expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh Tumor biopsy specimen
Subject must have an advanced solid tumor
Consent to undergo on treatment biopsy if tumor is accessible and safe to biopsy
Willingness to undergo a tumor biopsy prior to treatment.
Willingness to undergo a tumor biopsy while on study treatment.
Baseline tumor biopsy must be adequate
Carotid artery involvement by tumor had a neck dissection on that side
Patients with M1 stage according to the Tumor, Node and Metastasis Classification of Malignant Tumours (TNM)
Tumor HPV status established
The patient must have failed at least one line of standard treatment, with the following exceptions in which a PD-1 antibody is Food and Drug Administration (FDA) approved in the first-line setting: \r\n* Melanoma patients\r\n* Non-small cell lung cancer patients without EGFR or ALK genomic tumor aberrations whose tumors have high PD-L1 expression (tumor proportion score [TPS] >= 50%) as determined by an FDA-approved test
At least one measureable tumor lesion that that has not been previously locally
Invasion of the main portal vein and/or tumor involvement in more than 50% of the liver (applicable only for the dose-escalation part)
Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression
cMET dysregulated advanced solid tumor
Metastatic tumor that has been biopsied
Centrally assessed KIR3DL2 expression on tumor cells.
Uncontrolled tumor-related pain
Inclusion criteria include the following:\n\n          1. Is a male or female, ? 18 years of age, who has provided written informed consent.\n\n          2. Has histologically or cytologically confirmed advanced, unresectable, metastatic solid\n             tumor(s) for which the patients have no available therapy likely to provide clinical\n             benefit.\n\n          3. Must have an archival FFPE tumor sample available, to be provided to the Sponsor upon\n             request.\n\n          4. In the Expansion Phase: patients should be willing to undergo tumor core biopsy\n             procedure at pre-treatment and on Day 4, Cycle 1 if, in the judgment of the\n             investigator, it is considered clinically safe and appropriate to do so. This\n             requirement is optional but preferred for patients in Dose Escalation.\n\n          5. Has adequate organ function.\n\n        Women of childbearing potential must have a negative pregnancy test (urine or serum) within\n        7 days prior to starting the study drug. Both males and females and must agree to use\n        effective birth control during the study if conception is possible during this interval.\n\n        Exclusion:\n\n          1. Has received prior treatment with TAS-119.\n\n          2. Has received treatment with any proscribed treatments within specified time frames\n             prior to study drug administration.\n\n          3. Has a serious illness or medical condition(s).
Patients must be willing to forego other cytotoxic and non-cytotoxic drug or radiation therapy against the tumor while enrolled in the study.
Tumor foci detected below the tentorium or beyond the cranial vault.
30 days must have elapsed since previous treatment of the brain tumor with any other agents
Must not have a serotonin-secreting carcinoid tumor or a prior history of drug-induced serotonin syndrome
Sufficient tumor available to determine if expresses a mutation in KIT
Agreement to allow tumor to be evaluated for mutations in KIT and BRAF
Embolization procedure or ablation procedure to treat tumor within 4 weeks of first dose of STA-9090
All patients must have tumor specimens adequate for analysis of EGFR mutations and have tumor accessible to biopsy and must consent to biopsy.
Targeted tumor is at an impending fracture site of the weigh bearing bone (>7 on fracture risk score, see Section 6.9). OR o Patients with surgical stabilization of tumor site with metallic hardware
The targeted tumor(s) is (are) less than 2 points more painful compared to other non-targeted painful lesions on the site specific NRS.
Targeted tumor is in the skull
Target (most painful) tumor-bone interface is less then 1cm from nerve bundles, bowels or bladder.
Previous radiotherapy of the tumor bed (for ACC).
Histologically confirmed malignant solid tumor and not a candidate for known regimens or protocol treatments of higher efficacy or priority
The targeted tumor tissue is located in the cerebral hemispheres, > 2.5 cm from the inner table of the skull. Non-targeted parts of the tumor may extend outside the treated tumor limits.
Size of the targeted portion of the tumor (i.e. prescribed Region Of Treatment) is less than 2.5 cm in diameter or 8 cm3 in volume. The non-targeted tumor tissue may exceed the targeted volume.
Subjects with a total tumor size of ?2 cm following TURBT are eligible. Subjects with a tumor or tumors totaling >2 cm at screening must undergo a second debulking TURBT to reduce the tumor(s) to ?2 cm to be eligible for treatment.
Enough tumor material must be available for central confirmation of diagnosis, otherwise a new tumor biopsy is mandated.
The tumor specimen obtained at the time of diagnosis used for HER2 and ER/and PgR testing must also have central testing for PD-L1 status; patients who are negative or positive are eligible
The maximum tumor diameters for each Cohort for both Arm A and Arm B should achieve a dose of approximately 1x1011 viral particles (vp)/cm3 of tumor volume. (see Table 1). Please refer to Table for calculating tumor volume.
Favorable biomarker profile defined by either wild type p53 gene sequence or less than 20% p53 positive tumor cells by immunohistochemistry
Hepatic insufficiency not due to tumor resulting in clinical jaundice or bilirubin >1.5 x ULN and/or coagulation defects
mCRC currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
Measurable disease according to RECIST v1.1, and willingness to undergo a total of 2 biopsies of a primary or metastatic tumor site(s) considered safely accessible for biopsy.
Prior history of specific mutations (specified in the protocol) in the tumor at the time of any previous assessment.
Staining for PD-L1 in less than half of the tumor cells using the 22C3 antibody (0% staining is acceptable).
Immunohistochemistry (IHC) results from tumor biopsy for NY-ESO-1 positive
High FGFR mRNA expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh tumor biopsy specimen.
Expression of PD-L1 in ?50% of tumor cells determined by the commercially available assay performed by the central laboratory
Tumor >1.5 cm.
Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative soft-tissue mass of ~10-30 grams tissue (\grape\ to \golf-ball\ size) or pleural fluid estimated volume ? 500mL (from a primary or secondary thoracentesis, yielding in a high volume of tumor cells) for immunotherapy manufacture.
Tumor intended for immunotherapy manufacture is not embedded in bone and does not contain luminal tissue (e.g. bowel, ureter, bile duct).
History of other previous or concurrent cancer that would interfere with the determination of safety or efficacy assessment of RXDX-106 with respect to the qualifying solid tumor malignancy.
At least one lesion (metastasis or primary tumor) being considered accessible for a biopsy
Documented metastasis of the primary tumor to the CNS and not a candidate for surgical intervention nor require immediate radiation therapy to relieve symptoms
Methotrexate or non-BRAF/MEK non-cytotoxic anti-tumor drug ? 2 weeks
Tumor with androgen receptor (AR) expressed >= 4580 copies/ug ribonucleic acid (RNA)
Patients must have evidence of MIBG uptake into tumor at >= one site within 4 weeks prior to entry on study and subsequent to any intervening therapy
Prior therapy with tumor vaccine
RENAL COHORT: If the kidney primary tumor is in place this is the preferred site of biopsy
The subject has tumor invading or encasing any major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Histological or cytologically confirmed NSCLC that shows moderate or stronger mesothelin expression in 30% of tumor cells by a companion assay; MSLN expression score using Ventana immunohistochemistry (IHC) SP74 assay; Phase I only: In addition 5- 30% tumor cells and 1, 2, or 3+ MSLN score; Phase II only: 30% tumor cells and either 2+/3+
Patients must have completed standard radiation therapy with concurrent TMZ and must not have evidence of progressive disease on post treatment imaging. Progression can only be defined using diagnostic imaging if there is new enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line) or if there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas [i.e, > 70% tumor cell nuclei in areas], high or progressive increase in MIB-1 proliferation index compared with prior biopsy, or evidence for histologic progression or increased anaplasia in tumor). Note: Given the difficulty of differentiating true progression from pseudoprogression, clinical decline alone, in the absence of radiographic or histologic confirmation of progression, will not be sufficient for definition of progressive disease in the first 12 weeks after completion of concurrent chemoradiotherapy. (For Stage 1: Post-chemoradiation group only)
Tumor expression of NY-ESO-1 (2+ staining or > 25%) by immunohistochemistry (IHC).
Documented wild-type in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146) and in BRAF codon 600, based on tumor tissue taken from primary or metastatic site and tested for biomarkers
Diagnosis of an advanced solid tumor malignancy; there must be a target tumor which is measurable, palpable or clearly identifiable under ultrasound or radiographic guidance and amenable to percutaneous injection of C. novyi-NT spores; the targeted lesion must have a longest diameter ? 1 cm and < 12 cm and be measurable as defined by RECIST 1.1 criteria; the target lesion must not be located in either the thoracic, abdominal or pelvic cavities or in the brain; there must be no clinical, no functional, and no radiographic evidence of bone involvement at the site of the target lesion
Patient has a tumor sample from C. novyi-NT planned injected tumor lesion (newly obtained biopsy) for PD-L1 and immunologic response assessments; patients must submit the tumor sample during screening at a central pathology laboratory
PRE-REGISTRATION: Patients older than 21 years must have a solid tumor considered by study doctor to be of the childhood cancer type.
PRE-REGISTRATION: At least one documented histological verification of solid tumor diagnosis. Can be from original diagnosis or more recent.
Primary or recurrent retroperitoneal or abdominal tumor
Prior craniotomy and gross total or sub-total resection of tumor at this recurrence
Patients with non-bulky/non-bulky squamous cell carcinomas of the head and neck, with an indication for surgical therapy\r\n* T1N1-N2B, T2-4N0-N2b stage are generally eligible\r\n* If determined per tumor board that a low-volume/non-bulky tumor of another stage is appropriate for resection (e.g. small volume T4 with a small amount of bone invasion) such tumors may also be considered for this study if recommendation in tumor board is such
Tumor expressing PRAME and/or COL6A3.
Her-2 positive gastric tumor
Biopsy-accessible breast tumor of significant size for core needle biopsy (>= 2cm)
Histopathologic documentation any metastatic gastrointestinal tumor
T4 tumor
Have at least 1 of the tumor sites that must be amenable to core needle biopsy and this may not be the site of disease used to measure antitumor response
Surgery is done prior to IMT if needed for palliation, tumor debulking, pathological documentation of tumor recurrence; the patients may continue on study therapy even if they do not have measurable disease
Patients must have biopsiable tumor and agree to study biopsy
A tumor lesion that can be readily biopsied using a core needle via clinical exam or imaging-guidance
The patient must have measurable disease according to RECIST v1.1 and must have one site amenable to biopsy that, in the opinion of the investigator and/or interventional radiologist, is likely to yield acceptable tumor sample for a core biopsy per the below pathology criteria
Stratum 1: Recurrent or refractory primary malignant CNS tumor patients must have adequate pre-trial frozen or formalin-fixed paraffin-embedded (FFPE) tumor material (minimum of 10 unstained slides) available for use in the tumor mutation burden studies
Patients with bulky tumor on imaging are ineligible; bulky tumor is defined as:\r\n* Tumor with any evidence of uncal herniation or midline shift\r\n* Tumor that in the opinion of the site investigator, shows significant mass effect\r\n** 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
Tumor must have high Delta-like protein 3 (DLL3) expression defined as having ? 75% tumor cells staining positive according to the VENTANA DLL3 (SP347) IHC Assay.
Diagnosis during dose escalation (Part 1) - Pathologically documented, definitively diagnosed non-resectable advanced solid tumor.
All patients treated at doses > 120 mg per day must have medullary thyroid cancer (MTC), or a RET-altered solid tumor per local assessment of tumor tissue and/or blood.
Diagnosis during dose expansion (Part 2) - All patients in Groups 1, 2 and 4 must have a RET-altered (excluding synonymous and nonsense mutations) solid tumor, as determined by local testing of tumor or circulating tumor nucleic acid in blood; as detailed below.
Group 4 - patients must have a pathologically documented, definitively diagnosed advanced solid tumor with a RET alteration, other than NSCLC and MTC.
For the expansion patients must provide a fresh tumor biopsy at enrolment
An interval of at least 12 weeks from the completion of radiation therapy to start of study drug unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field (defined as the region outside the high-dose region or 80% isodose line) or there is unequivocal histologic confirmation of tumor progression
Well-differentiated (G1 or G2) based on local pathology report, non-functional neuroendocrine tumor of GI, pancreatic or thoracic (including lung and thymus) origin.
Tumor biopsy material must be provided for all patients for the purpose of biomarker analysis
Phase 2 only: Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy
Gross total or partial tumor resection is not possible or not planned
A single measurable tumor that is at least 10.0 mm longest diameter (LDi) X 10.0 mm shortest diameter (SDi) and this tumor does not exceed 40.0 mm in LDi or SDi on Screening MRI
Tumor location on both sides of the brain and/or involvement that would present the risk of injecting DNX-2401 into the ventricles of the brain
Tumor location in the brain stem
Simultaneous primary cancers or separate bilateral primary tumor sites.
Willing to undergo tumor biopsies from injected and distal lesions
The primary tumor must be excised via breast conserving surgery (“lumpectomy”) with negative margins (no ink on tumor) in the final specimen
The tumor must be =< 2 cm (T1) in the largest dimension
The invasive component of the tumor has a grade 3 histology
The subject has tumor in contact with, invading or encasing any major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
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: \r\n* Distance of the lowest tumor margin from the anal verge; and \r\n* Intent for sphincter sparing or non-sphincter sparing surgical resection according to the primary surgeon; and\r\n* 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
Patient must have adequate tumor specimen available for submission
Patients with primary refractory disease with progression of the primary tumor on initial therapy
Subjects with histologically confirmed CNS embryonal tumor (primitive neuroectodermal tumor [PNET], medulloblastoma, atypical teratoid rhabdoid tumor [ATRT], medulloepithelioma, pineoblastoma or ependymoblastoma), or germ cell tumor, are eligible; tumors must be relapsed or refractory to first-line therapy; diagnosis will be made on the basis of computed tomography (CT)-assisted or stereotactic biopsy, open biopsy, surgical resection, cerebrospinal fluid (CSF) cytology, or elevated tumor markers
The subject has an infra-tentorial tumor or multifocal disease
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
Patients must have had no prior radiotherapy to tumor-involved sites
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
Willing to undergo a baseline tumor core needle biopsy for correlative science studies; this study does not restrict eligibility based on PD-L1 expression
Subjects who are willing and able to comply with the protocol and study procedures including willingness to undergo tumor biopsy for tumor cells before therapy at cycle 1, day 1, and day 8 (before cisplatin dose) if this is clinically and safely feasible to do so
In addition, patients with NF1 and with malignant peripheral nerve sheath tumor (MPNST)
TREATMENT: Patient must have predefined targeted mutation in tumor biopsy
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)
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
Diagnosis of MPM, confined to single pleural cavity, with histologic confirmation of the primary tumor
Patients who have measurable residual tumor at the primary site
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); tumor biopsies will be performed on the most accessible biopsable site of disease; all possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed; patients affected by glioma will not be considered for study biopsies
Any tumor-specific or clinical features that make surgical intervention unsafe in the opinion of the treating neurosurgeon
Patients must be willing to undergo 2 tumor biopsies
Maximum diameter of enhancing tumor (target lesion) should be =< 4 cm
Has recurrent or persistent tumor (enhancing area) greater than 4 cm in maximum diameter
Cohort 2 (MTD) only: patient willing to have paraffin-embedded slides of the primary pancreas tumor or metastatic site, if available, sent to Mayo investigators for this study
Participants must have recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report
Willing to consent to allow access to known archival tumor tissue (NOTE: designated pathologist from participating site OR lead principal investigator must sign-off to ensure “sufficient” tumor should be available for support of tumor imaging studies [multi-color immunofluorescence])
For enrollment in the first stage of Cohort B, patients must have accessible pre-treatment and post-treatment (4-6 weeks) tumor for biopsy
The tumor must be primarily supratentorial in location as determined by diagnostic imaging performed preoperatively
Radiographic contrast enhancement attributable to residual tumor on post-operative imaging performed within 72 hours of resection must not exceed 1 cm in biperpendicular planes (> 1 cm in one plane but < 1 cm in other planes will be allowed)
Adequate tumor content as determined by institutional pathologist for nucleic acid extraction and DNA sequence analysis
Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal dissemination, gliomatosis cerebri or infratentorial tumor
Pathologic proven diagnosis of solid tumor malignancy
Cohort II (MTD): willing to provide the biologic specimens as required by the protocol; note: this is part of the mandatory translational research component; note: patients with the only tumor accessible for biopsy in the pancreas will not be eligible as core biopsies are associated with significant increase in risk for the patient
The subject has tumor in contact with, invading or encasing any major blood vessels
Recipient leukocyte infusion (RLI) might involve the infusion of circulating tumor cells to the patients; to minimize this risk, patients who have evidence of circulating tumor cells by light microscopy and flow cytometry will be excluded
Patients with acute leukemia will be excluded because they will likely have a much greater circulating tumor burden, which would increase the risk of infusion of clonal tumor cells
Diagnosis of \tumor of low-malignant potential\.
Patients with confirmed p53 mutation by molecular analysis and/or evidence of p53 overexpression by immunohistochemistry (>= 10% of cells within tumor staining positive) will be eligible; this will be assessed semi-quantitatively by a Clinical Laboratory Improvement Act (CLIA) approved pathology core pathologist, using CLIA approved mutational analysis or immuno-histochemistry techniques on formalin-fixed paraffin-embedded tissue; in the case of equivocal immunohistochemistry (IHC) results, p53 involvement may be confirmed by detection of p53 molecular analysis on tumor deoxyribonucleic acid (DNA); patients on whom molecular analysis of p53 mutations is already available, will not require IHC analysis; molecular analysis may be performed as an additional research procedure at the end of the study (distinct from eligibility determination) if the principal investigator (PI) deems it of scientific value and research funding is available to cover the cost; patients must have PD-L1 positive ovarian cancer in order to be eligible for this clinical trial (defined as >= 1% PD-L1 expression within the tumor section, assessed by immunohistochemical staining)
The T stage must be Tis, T1, or T2; if T2, the tumor must be =< 3.0 cm in maximum diameter
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\r\n* NOTE: this may include cutaneous and subcutaneous tumors using injection by palpation or ultrasound guidance\r\n* NOTE: the target lesion must be >= 1.5 cm on its longest diameter, be at least 5 mm thick, and have distinct borders\r\n* 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\r\n* 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
The tumor location must be suitable for either lobar or sublobar resection (wedge or segment)
Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible for study entry
Patients with anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor
Brain tumor patient is planning to undergo tumor resection or biopsy for the purpose of differentiating between tumor progression versus treatment-induced effects following radiation therapy and/or chemotherapy\r\n* If a patient has magnetic resonance imaging (MRI) findings consistent with tumor but does not already have a histopathologic diagnosis of cancer, s/he may sign the consent form, but final eligibility for study enrollment will be determined based on results of the frozen section at time of surgery
Macrovascular tumor invasion of portal and/or hepatic vein(s)
Extracapsular tumor extension
Biopsy accessible tumor deposits
Subjects must have positive mesothelin expression in the archival tumor tissue, defined as the mesothelin membrane intensity score of 2+ or 3+ (on the 0-3 scale) expressed on the membrane of >= 10% of tumor cells
Uncontrolled tumor-related pain
Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse \r\n* Primary strata\r\n** Wilms tumor\r\n** Rhabdomyosarcoma\r\n** Neuroblastoma\r\n* Secondary strata: miscellaneous CD56-expressing tumors:\r\n** Pleuropulmonary blastoma\r\n** Malignant peripheral nerve sheath tumor (MPNST)\r\n** Synovial sarcoma
Confirmed p53 involvement: patients with p53 over-expression by immunohistochemistry (>= 10% of cells within the tumor staining positive) or those with a p53 mutation as determined by mutational analysis of tumor tissue will be eligible; patients with prior exposure to p53-based vaccines will be eligible
Patients must be untreated with curative-intent surgery for current diagnosis of stage III, IVa, or IVb disease; diagnostic biopsy of primary tumor and/or nodal sites is permitted\r\n* Diagnostic simple tonsillectomy is permitted, provided patient has Response Evaluation Criteria in Solid Tumors (RECIST)-measurable nodal disease\r\n* Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy), and has not recurred
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
p16 positive by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells, confirmed by central pathology review)
COHORT EXPANSION PHASE: At least one tumor lesion amenable to core needle biopsy without unacceptable risk of a major procedural complication (one pretreatment and at least one on-treatment biopsy will be performed)
Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
Osteosarcoma, neuroblastoma and melanoma that have been treated with standard frontline therapy and are judged to be incurable with standard therapy, based upon the fact that they are unresectable, metastatic, progressive/persistent or recurrent; evaluable disease must be present\r\n* For all histologies except osteosarcoma and neuroblastoma, pathologic review of frozen tissue must document GD2+ expression; positive expression is defined as at least 2+ expression (0-4+ scale) in > 50% of the tumor cells using anti-GD2 monoclonal antibody (mAb) 14G2a; if adequate archived frozen tissue is available, this may be utilized, or if not, patients may undergo biopsy following enrollment to obtain tissue to assess GD2 expression, with the following restrictions\r\n* Patients with histologies other than osteosarcoma or neuroblastoma must have adequate accessible tumor for biopsy (at least 1 cm diameter)\r\n* Procedures employed to acquire biopsies for tumor lysates will be limited to percutaneous needle or core biopsies, thoracoscopic excision or open biopsies of readily accessible lesions; pulmonary lesions may be biopsied but extensive surgery such as thoracotomy or laparotomy should not be employed\r\n* Patients who will require biopsy should not be enrolled if in the opinion of the principal investigator, the tumor site places the patient at substantial risk from the biopsy procedure
Patients must have recurrent or persistent ovarian, fallopian tube, peritoneum, and endometrial clear cell carcinoma; primary tumors must be at least 50% clear cell histomorphology in order to be eligible or have a histologically documented recurrence with at least 50% clear cell histomorphology; in addition, the tumors should be negative for expression of Wilms tumor 1 (WT-1) antigen (with the exception of endometrial cancers where WT-1 stains are not required) and estrogen receptor (ER) antigen by immunohistochemistry; focal, weak, ER staining of tumor cells (< 5%) is permitted; appropriate tissue sections must be available for histologic evaluation for central pathology review by Gynecologic Oncology Group (GOG); immunohistochemical stained slides for ER and WT-1 antigen must be available for review by GOG\r\n* If the primary tumor had at least 50% clear cell histomorphology, a biopsy of the recurrent or persistent tumor is not required; however, immunohistochemical studies of the primary tumor for ER and WT-1 antigens should be performed and the slides submitted to the GOG for review; the percentage of clear cell histomorphology must be documented in the pathology report or in an addendum to the original report; if slides of the primary tumor are not available for review due to disposal of slides by the histology laboratory (typically 10 years after diagnosis), biopsy of recurrent or persistent disease is required\r\n* If the primary tumor had less than 50% clear cell histomorphology (or if slides of the primary tumor are not available for review), a biopsy of the recurrent or persistent tumor is required to confirm at least 50% clear cell histomorphology and lack of immuno-reactivity for ER and WT-1 antigens by immunohistochemistry; the percentage of involvement must be documented in the pathology report or in an addendum to the original report
Pre-surgery tumor deemed amenable to core biopsy (with at least 100 mm^3 tumor volume per biopsy)
Imaging studies show evidence of recurrent, supratentorial tumor(s); the presence of infratentorial tumor is allowed as long as the patient also has supratentorial disease that is amenable to resection or biopsy
The patient must be in need of a craniotomy for tumor resection or a stereotactic brain biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy
Based on the neurosurgeon's judgement, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
Submission of tumor samples is required for all patients; the local pathology department policy regarding release of tumor samples must be considered in the screening process; patients whose tumor samples are located in a pathology department that by policy will not submit any samples for research purposes should not be approached for participation in the B-52 trial
Documented laboratory (lab) results confirming tumor mutational status must be obtained at screening; patients in whom mutational status cannot be determined will be deemed ineligible
Unresectable stage III or IV validated by clinical criteria (including recurrent melanoma), or patients with multiple skin/soft tissue metastases of melanoma that may be resectable but are judged to have a future recurrence risk exceeding 70% (e.g., large adenopathy, distant skin metastases or multiple in-transit melanoma metastases); tumor deemed amenable to biopsy (excisional, incisional, or core, with at least 100 mm^3 tumor volume per biopsy date) and fine-needle aspiration (FNA) biopsy\r\n* NOTE: optimally, patients will have tumor approachable for three serial biopsies during the trial; for patients with only one or two tumors approachable for biopsy, available tumor blocks from prior biopsies can serve as the pretreatment sample, but only if formalin-fixed tumor tissue is available and adequate to provide at least 20 unstained slides with sufficient tumor for analysis\r\n* NOTE: patients with unresectable advanced stage III or IV melanoma (including recurrent melanoma) are only eligible if they have failed at least one other first-line systemic therapy (other than adjuvant therapy); exceptions to this requirement are those patients who have refused and/or are ineligible for other systemic therapies\r\n* NOTE: v-raf murine sarcoma viral oncogene homolog B inhibitor (BRAFi) should be considered for all ‘unresectable” or metastatic melanoma with BRAFV600E mutation; for low burden in-transit disease patients may enter trial without prior systemic therapy\r\n** Stage IV no evidence of disease (NED) is excluded by this criterion
Patient must agree to allow 3 separate biopsies of any malignant lesion; biopsies do not need to be done if:\r\n* 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)\r\n* Patient is on anticoagulation and it would be unsafe to temporarily hold the anticoagulation\r\n* Consent of the principal investigator (PI) not to have a biopsy done\r\n* A minimum of 8 subjects must participate in the biopsy part of the study
Tumor diameter =< 7 cm
Inclusion Criteria (summary):\n\n          -  Age between 18 and 75 years (inclusive) at screening.\n\n          -  Karnofsky performance status (KPS) of 70 or higher or Eastern Cooperative Oncology\n             Group (ECOG) 0-1 at screening.\n\n          -  Subjects with a histological or cytopathological confirmed diagnosis of a locally\n             advanced or metastatic solid tumor malignancy for which primary treatment is no\n             longer effective or does not offer curative or life-prolonging potential per\n             clinician judgment, with the understanding that DCVax-Direct is not intended as a\n             treatment of last resort.\n\n          -  Not eligible for complete resection due to either tumor location, physician's\n             assessment or subject's choice.\n\n          -  Must have completed at least one recent treatment regimen in the metastatic or\n             advanced setting in the disease currently under treatment to reduce tumor burden.\n\n          -  Any steroid therapy >2 mg dexamethasone or equivalent dose should be stopped or have\n             been tapered down 2 weeks prior to the leukapheresis.\n\n          -  At least one measurable tumor mass, i.e. a lesion that can accurately be measured by\n             CT/MRI in at least one dimension with longest diameter ? 1 cm, that is accessible for\n             injection either with or without imaging (CT/ultrasound) guidance.\n\n          -  Adequate hematological, hepatic, and renal function,\n\n          -  Adequate blood coagulation parameters\n\n          -  Life expectation of >3 months.\n\n        Exclusion Criteria (Summary):\n\n          -  Positive HIV-1, HIV-2, or Human T-lymphotropic virus (HTLV-I/II) tests.\n\n          -  History of current or prior (within the last two years) active clinically significant\n             malignancy other than the tumor type for which DCVax-Direct treatment is considered,\n             and except for primary tumor in the case of metastases and adequately treated basal\n             cell or squamous cell skin cancer or in situ cervical cancer.\n\n          -  Heavily pretreated (HP) subjects are not eligible for this study, unless treatments\n             have occurred more than 1 year in the past.\n\n          -  Presence of brain metastases, unless treated surgically and/or irradiated and\n             clinically stable off steroids or on low dose (< 2 mg per day) steroids for ? 14\n             days, or presence of leptomeningeal disease.\n\n          -  History of immunodeficiency or unresolved autoimmune disease.\n\n          -  Requirement for ongoing immunosuppressants.\n\n          -  Prior active immunotherapy for cancer within the past 2 years.\n\n          -  Ongoing medical need for continuous anti-coagulation or anti-platelet medication.\n\n          -  Known genetic cancer-susceptibility syndromes.\n\n          -  Acute or active uncontrolled infection\n\n          -  Ongoing fever ? 101.5 degrees F/38.6 degrees C at screening.\n\n          -  Unstable or severe intercurrent medical conditions such as unstable angina,\n             uncontrolled arrhythmias, Crohn's Disease, ulcerative colitis etc.\n\n          -  Females of child-bearing potential who are pregnant or lactating or who are not using\n             adequate contraception (surgical, hormonal or double barrier, i.e. condom and\n             diaphragm).\n\n          -  Allergy or anaphylaxis to any of the reagents used in this study.\n\n          -  Inability to obtain informed consent because of psychiatric or complicating medical\n             problems.\n\n          -  Inability or unwillingness to return for required visits and follow-up exams.
Inclusion Criteria (summary):\n\n          -  Age between 18 and 75 years (inclusive) at screening.\n\n          -  Karnofsky performance status (KPS) of 70 or higher or Eastern Cooperative Oncology\n             Group (ECOG) 0-1 at screening.\n\n          -  Subjects with a histological or cytopathological confirmed diagnosis of a locally\n             advanced or metastatic solid tumor malignancy for which primary treatment is no\n             longer effective or does not offer curative or life-prolonging potential per\n             clinician judgment, with the understanding that DCVax-Direct is not intended as a\n             treatment of last resort.\n\n          -  Not eligible for complete resection due to either tumor location, physician's\n             assessment or subject's choice.\n\n          -  Must have completed at least one recent treatment regimen in the metastatic or\n             advanced setting in the disease currently under treatment to reduce tumor burden.\n\n          -  Any steroid therapy >2 mg dexamethasone or equivalent dose should be stopped or have\n             been tapered down 2 weeks prior to the leukapheresis.\n\n          -  At least one measurable tumor mass, i.e. a lesion that can accurately be measured by\n             CT/MRI in at least one dimension with longest diameter ? 1 cm, that is accessible for\n             injection either with or without imaging (CT/ultrasound) guidance.\n\n          -  Adequate hematological, hepatic, and renal function,\n\n          -  Adequate blood coagulation parameters\n\n          -  Life expectation of >3 months.\n\n        Exclusion Criteria (Summary):\n\n          -  Positive HIV-1, HIV-2, or Human T-lymphotropic virus (HTLV-I/II) tests.\n\n          -  History of current or prior (within the last two years) active clinically significant\n             malignancy other than the tumor type for which DCVax-Direct treatment is considered,\n             and except for primary tumor in the case of metastases and adequately treated basal\n             cell or squamous cell skin cancer or in situ cervical cancer.\n\n          -  Heavily pretreated (HP) subjects are not eligible for this study, unless treatments\n             have occurred more than 1 year in the past.\n\n          -  Presence of brain metastases, unless treated surgically and/or irradiated and\n             clinically stable off steroids or on low dose (< 2 mg per day) steroids for ? 14\n             days, or presence of leptomeningeal disease.\n\n          -  History of immunodeficiency or unresolved autoimmune disease.\n\n          -  Requirement for ongoing immunosuppressants.\n\n          -  Prior active immunotherapy for cancer within the past 2 years.\n\n          -  Ongoing medical need for continuous anti-coagulation or anti-platelet medication.\n\n          -  Known genetic cancer-susceptibility syndromes.\n\n          -  Acute or active uncontrolled infection\n\n          -  Ongoing fever ? 101.5 degrees F/38.6 degrees C at screening.\n\n          -  Unstable or severe intercurrent medical conditions such as unstable angina,\n             uncontrolled arrhythmias, Crohn's Disease, ulcerative colitis etc.\n\n          -  Females of child-bearing potential who are pregnant or lactating or who are not using\n             adequate contraception (surgical, hormonal or double barrier, i.e. condom and\n             diaphragm).\n\n          -  Allergy or anaphylaxis to any of the reagents used in this study.\n\n          -  Inability to obtain informed consent because of psychiatric or complicating medical\n             problems.\n\n          -  Inability or unwillingness to return for required visits and follow-up exams.
No tumor in contact with, invading or encasing any major blood vessels
No evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of treatment
No evidence of tumor potentially causing airway obstruction
Pretreatment tumor biopsy with sufficient tumor for HPV or p16 analysis is required; the tumor must be HPV(+) or p16(+)
Patients must have, in the opinion of a treating physician, tumor that is accessible to biopsy in the clinic
Note: optional tumor biopsies (punch, fine needle aspiration [FNA], core or excisional) at pre-treatment, week 1, and at progression will be presented to subjects considering this study; we anticipate approximately 1-3 patients per cohort to have tumors biopsied for correlative studies; the additional subjects at the recommended phase II dose (RP2D) (expansion cohort) are required to have correlative studies (blood collection and tumor biopsies at the defined time points)
All patients who have received prior chemotherapy for histologically proven advanced non-small cell lung cancer, and whose tumors display the appropriate phenotype, i.e. high ISG15 (ISG15H), are eligible; results of tumor screening will be sent in writing from Lovelace Respiratory Research Institute within 14 days of submitting tumor specimens for screening; screening may occur prior to failure of frontline, second, or third line regimen\r\n* Note: A separate informed consent document will be available for patients to undergo screening for ISG15H status
Subjects with a histologic diagnosis of solid tumor cancers of epithelial origin.
Patients by definition have disease at the primary tumor site of at least 2 centimeters
Patient’s treatment plan must include primary tumor site biopsy followed by gross excision of the primary tumor site at a separate operative procedure
Patients with T4 disease with radiographic evidence of massive invasion of a large pulmonary artery and tumor causing significant narrowing and destruction of that artery are excluded
Presence of appropriate size and site of viable tumor tissue for safe tumor biopsy collection (the biopsy is optional and requirement is only applicable to subjects considered for the expansion cohort stage of the study)
Ability and willingness to undergo repeat tumor biopsies (the biopsy is optional and only applicable to subjects considered for the expansion cohort stage of the study)
If tumor size is < 1 cm on mammography and all calcifications are removed on core biopsy the patient will be excluded
Inoperable tumor or residual disease after resection
Pathologic proven diagnosis of solid tumor malignancy
Positive staining of tumor tissue with antibodies to 1 or more of the following: human melanoma black (HMB) 45 for gp100, or cancer-testis antigen (NY-ESO-1)
Patients must have a paraffin embedded tumor specimen from the kidney or metastatic site available for central review of tumor histology; tumor samples will be shipped as specified
At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
Patients are preferred to have either a tumor mass amenable to core needle biopsy during the dosimetry phase, or a measurable tumor mass with at least one site of involvement measuring 2.0 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission CT (SPECT)/CT tumor dosimetry (patients with disease that does not allow tumor dosimetry will be allowed on study since they still can contribute toward achieving the primary endpoint, but these patients will be given a lower priority over those with evaluable disease)
Tumor in a location where enlargement could cause airway obstruction
Folate receptor alpha positive tumor expression as defined in the protocol
All visible papillary tumors must be resected and those with persistent T1 disease on transurethral resection of bladder tumor (TURBT) should undergo an additional re-TURBT within 14 to 60 days prior to beginning study treatment. Obvious areas of CIS should also be fulgurated.
Patients with T1 disease accompanied by the presence of hydronephrosis secondary to the primary tumor
Patients must have had progressive disease on, after, or refused, appropriate approved therapy for their tumor type.
Patients must harbor a tumor HER2/neu+ based upon IHC staining score of “3+” or 2+ with confirmed gene amplification by FISH to be included
Rhabdoid tumor:
NI1-negative tumor:
Epithelioid malignant peripheral nerve sheath tumor
Epithelioid malignant peripheral nerve sheath tumor
Uncontrolled tumor-related pain
DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment of banked or otherwise representative tumor tissue. Positive is defined as staining in ? 1% of tumor cells.
Subjects (NSCLC and gastric adenocarcinoma) must be determined to have HA-high levels from their tumor biopsies.
Patients must have stage cT2-T4a N0 M0 disease; clinical T stage is based on the transurethral resection of bladder tumor (TURBT) sample and imaging studies; patients must undergo cystoscopy and TURBT as part of the staging procedure within 56 days prior to registration; to exclude non-bulky/low-risk tumors and ensure adequate tissue for assessment, subjects must have documented muscle invasion with at least one of the following:\r\n* Disease measuring at least 5 mm on cross-sectional imaging or by endoscopic assessment; bladder thickening on imaging without definable tumor is not adequate; pathology verification of >= 0.5 cm of viable tumor (longest diameter) from the biopsy sample and represented on the submitted slides is also acceptable\r\n* The presence of tumor-associated hydronephrosis
Patients must be offered the opportunity to participate in the ultra pure Circulating Tumor Cells (upCTCs) study
Tumor sample must be available for analysis of PDL1 (Programmed death-ligand 1) and HPV [Human Papilloma Virus (oropharynx only)]
Patient must agree to undergo central tumor HRD testing
Test result showing genetic change in MET tumor gene
At least one tumor that can be measured on a radiographic scan
Uncontrolled tumor in the brain
Participants must have shown unequivocal evidence of tumor progression.
Patient is after surgical resection of the tumor where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical specimen
Part 4: select advanced solid tumor or hematologic malignancy
Fresh baseline tumor biopsies (defined as a biopsy specimen taken since completion of the most recent prior chemotherapy regimen) are required for all cohorts except glioblastoma
MSI status is, respectively, determined by examining CRC tumor.
Patients must have evidence of MIBG uptake into tumor at ? one site within 4 weeks prior to entry on study and subsequent to any intervening therapy.
Patients must have recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report
Baseline archival tumor specimen available or willing to undergo a prestudy treatment tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain the specimen.
Provide a baseline tumor biopsy
Tumor shown to be human epidermal growth factor 2 plus (HER2+)
Tumor specimen positive for NY-ESO-1 expression by IHC.
Newly obtained tumor biopsy from metastatic site
Patient must have archived primary tumor biopsies or surgical specimens, or biopsies of recurrent or metastatic samples
Patient must be amenable to serial peripheral blood sampling, urine sampling, and tumor biopsies during the study
Patients must agree to undergo tumor HRD testing and blood gBRCAmut status testing.
Uncontrolled tumor-related pain.
Non epithelial tumor or ovarian tumors with low malignant potential (ie, borderline tumors).
Tumor specimen positive for NY-ESO-1 expression by IHC and/or RT-PCR. At least one tumor must be accessible and patients must consent for biopsies in Arms C and D.
Non-GI solid tumors (like non-small cell lung cancer or breast cancer) should have confirmed CEA expression in tumor tissue >/= 20% of tumor cells staining with at least moderate to high intensity of CEA expression are required (immunohistochemistry [IHC]2+ and IHC 3+). For CRC, pancreatic and gastric cancer participants, the CEA assessment will be performed retrospectively and the result is not needed to enroll the participant. For the biomarker cohort, only participants with moderate/low CEA expression (< 20% of tumor cells with IHC2+/3+ and/or >/= 20% of tumor cells with IHC1+) and very low CEA expression (< 20% of tumor cells with IHC1+) will be enrolled. CEA expression should be determined prior to enrollment, if no archival tumor tissue is available, a fresh biopsy will be collected.
Confirmed availability of representative tumor specimens in paraffin blocks/unstained slides
Documented HER2 overexpression or gene-amplified tumor by a validated approved method
For certain subjects, willing and able to provide pre-treatment and on-treatment fresh tumor biopsy
KRAS or NRAS mutation detected in tumor specimen
Tumor in contact with, invading or encasing any major blood vessels found on radiology report
Evidence of endotracheal or endobronchial tumor
Tumor tissue (primary or cervical metastasis) available for human papilloma virus (HPV) and/or tumor protein (p) 16 (in situ hybridization [ISH], immunohistochemistry [IHC] or genotyping testing); if you do not have enough leftover tumor tissue available, you will have a tumor biopsy for tumor marker testing
If primary tumor has not been resected, it must be clinically stable
Total (aggregate) gross tumor volume > 500 cm^3 (500 cc’s or 0.5 liters)
Histologically confirmed high-grade upper tract transitional cell carcinoma at Memorial Sloan-Kettering Cancer Center (MSKCC) or a participating site and/or radiographically visible tumor stage T2-T4a N0/X M0 disease with positive selective urinary cytology; hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition
The tumor is unresectable and not amenable to curative therapy.
Has an adequate tumor sample
Tumor accessible for biopsy
Must be willing to undergo tumor biopsy at study entry for biologic correlates.
If patient > 18 years, must be willing to undergo on-treatment tumor biopsy unless medically contra-indicated
Five grams of resected tumor available for vaccine manufacture as determined by institutional pathologist; seven grams of tumor is preferred
First recurrence after concurrent or adjuvant chemoradiotherapy. Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria . A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling.
The subject is willing to undergo tumor biopsy during the Screening period, or if the tumor is inaccessible for biopsy, archived tumor material must be available for submission;
Participants must have histological diagnosis consistent of Anaplastic Thyroid Cancer (ATC). Cytologic diagnosis by fine needle aspiration alone is not sufficient. Histologic diagnosis may be made by core needle biopsy, incisional biopsy, thyroidectomy, or other surgical biopsy. Fresh tumor biopsies (re-biopsy) should be obtained whenever feasible. The central pathology review may take place prior to or after the participant starts treatment with lenvatinib.
Subjects must have a previously treated advanced solid tumor to be eligible
Willing and able to provide pre-treatment and on-treatment fresh tumor biopsy
All subjects must consent to provide archived tumor specimen
Tumor specimen availability
Solid tumors with tumor-induced pain
Subject must not have been treated previously with talimogene laherparepvec or tumor vaccine.
Tumor histology consistent with melanoma tumor specimen positive for NY-ESO-1 expression by IHC and/or RT-PCR.
Presence of multiple small bowel loops trapped within the immediate tumor bed (post hysterectomy or prostatectomy)
A tumor accessible for biopsies and consent to undergo tumor biopsies before and during MSC2363318A treatment. Subjects who do not have a tumor suitable for biopsy (such as, but not limited to, high procedural risk, inaccessible site for needle biopsy, etc.) but are otherwise eligible for this study may be considered for enrollment on a case-by-case basis after discussion with the Medical Monitor of the study
Patients with gross residual or metastatic tumor findings following complete surgical treatment for uterine LMS
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\r\n* 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)
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
Non-antibody immunotherapy (e.g., tumor vaccine) At least 42 days
Archival tumor samples must be obtained from primary and/or metastatic sites
If archival tumor is available for submission, patients must be willing to submit tumor sample
Single enhancing lesion that is >1 cm, but < 4 cm in cross-sectional dimension, including thalamic tumor (? 3 cm)
Symptoms due to mass effect of the tumor including high intracranial pressure, marked edema or ?5mm midline shift significant
Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [Tumor, node, metastases (TNM)] clinical staging system).
Resected tumor: No evidence of gross tumor at the surgical resection margin noted in the final surgery report. No evidence of gross residual adenopathy
Primary tumor is available for shipment to central laboratory for analysis of FR? expression by IHC.
Patients must have tumor (paraffin block or slides) available for submission and be willing to submit tumor and blood samples
Human epidermal growth factor receptor 2 (HER2)-negative tumor (primary tumor or metastatic lesion)
HER-2 negative tumor (primary tumor or metastatic lesion)
Histologic or cytologic documentation of metastatic or Stage IIIc unresectable melanoma, with BRAFV600 mutation as assessed by BRAFV600 Mutation Test. Origin of the primary tumor may be of skin, mucosal, or acral locations but not of uveal origin. Participants having an unknown primary tumor may be eligible if uveal melanoma can be ruled out
ECOG Performance Status score of 0 or 2 for subjects with NMC; 0-1 for subjects with other tumor types.
Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report
Histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection (i.e., patients with rectal cancer are not eligible); surgeon confirmation that the entire tumor was above the peritoneal reflection is only required in cases where it is important to establish if the tumor is a rectal or colon primary
Non-antibody immunotherapy (e.g., tumor vaccine); at least 42 days since last dose
Date of Mayo Clinic Genomics Tumor Board review =< 3 months prior to registration
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL
Have at least one untreated and progressing tumor lesion that can be accurately measured according to Response Evaluation Criteria in Solid Tumor
A fresh tumor biopsy for the purpose of screening or an available archival tumor sample. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy.
Anticipated treatment of the index tumor that would require iceball formation within 0.5 cm of the spinal cord, brain, other critical nerve structure, large abdominal vessel (possibly achieved with additional maneuvers such as hydrodissection)
Index tumor involves the skull
Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Histologic documentation of the original primary tumor is required via the pathology report.
Solid tumor contact with SMA > 180°
Tumor MGMT promoter hypermethylation determined by central testing at MD Anderson
History of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the participant has undergone potentially curative therapy with no evidence of that disease for 5 years
Histologic diagnosis of a benign or borderline tumor (‘tumor of low malignant potential’) or of a malignant tumor of non-epithelial origin (such as a germ cell tumor, sex-cord stromal tumor) of the ovary, fallopian tube or peritoneum
A representative tumor specimen must be available for molecular testing.
Patients who have had gross total excision of the primary tumor.
Patients with primary tumor of oral cavity, nasopharynx, sinuses or salivary glands.
Tumor replacement > 70% of total liver volume based on visual estimation by investigator OR tumor replacement >50% of total liver volume in the presence of albumin <3 mg/dL
Patients with placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT)
Documentation of ER positive (? 1% positive stained cells by local standards) based on the most recent tumor biopsy, unless bone-only disease
Documented HER2-negative tumor based on local testing on most recent tumor biopsy (immunohistochemistry score 0/1+ or negative by in situ hybridization HER2/CP17 ratio < 2 or for single probe assessment HER2 copy number < 4)
Tumor sites that can be accessed for repeat biopsies
Uncontrolled tumor-related pain
Operable tumor measuring >= 1.5 cm in maximal diameter\r\n* Any nodal status\r\n* Multifocal and multicentric disease is permitted\r\n* Synchronous bilateral invasive breast cancer is permitted\r\n* The tumor should be more than 5 mm from the skin
Tumor amenable to cryoablation as determined by radiologist
predominantly epithelial (?50% tumor component) pleural or peritoneal mesothelioma
have at least 1 measurable lesion assessable by radiological imaging. Tumor lesions located in a previously irradiated area are considered measureable if progression has been demonstrated in such lesions
Cohort C: Histologically confirmed metastatic solid tumor of epithelial origin, including both NSCLC and non-NSCLC, with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that requires corticosteroids for symptomatic control
Tumor of the oropharynx
Tumor involvement of the following sites or any of these signs or symptoms likely to be associated with T4b cancer:
gross extension of tumor to the skull base;
Tumor
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
Inoperable, locally recurrent or metastatic disease (tumor resectability should be assessed by a local surgeon or multidisciplinary team)
Locally recurrent tumor which is amenable to curative resection (as deemed by a local surgeon or multidisciplinary team)
Tumor relapse/progression within 6 months of completion of a cisplatin-based chemoradiotherapy regimen for the treatment of early stage tumors
Previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable locally recurrent or metastatic tumors (previous use of radiotherapy or chemotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumor lesions are present at randomization for the purpose of tumor response assessment or 2) in the absence of non-irradiated target tumor lesions, progression of the irradiated tumor lesions according to the RECIST criteria version 1.1 is documented)
Uncontrolled tumor pain
Participation in Iowa Neuroendocrine Tumor Registry
A pre-treatment tumor biopsy demonstrating high TAM content as assessed per the central laboratory
Planned resection of primary tumor
Primary tumor diameter ?40 mm
Evidence of remaining tumor
Submission of copies of tumor measurements and scans
Prior treatment with another experimental anti-tumor vaccine is permissible
Subjects must have archival tumor tissues or agree to a tumor biopsy for analysis of predictive biomarkers such as PD-L1. (Fresh tumor biopsies are strongly recommended at baseline for biomarker analysis in subjects with readily accessible tumor lesions and who consent to the biopsies.)
Consent to paired tumor biopsy, for accessible tumors
Patients must be able to enter into the study within ten weeks of their most recent diagnostic procedure, which is usually a diagnostic biopsy, a transurethral resection of bladder tumor (TURBT) procedure or positive urine cytology.
Patients with well-differentiated neuroendocrine carcinoma (carcinoid tumor)
Patients with one-sided, somatic pain due to tumor involvement below the shoulder level (C5 dermatome)
Patients with a history of obstructive jaundice due to the primary tumor must have a metal biliary stent in place
Maximum diameter of enhancing tumor (target lesion) should be =< 3.5 cm
Has recurrent or persistent tumor (enhancing area) greater than 3.5 cm in maximum diameter
At least 1 of the tumor sites must be amenable to core needle biopsy and this may not be the site of disease used to measure antitumor response
Primary tumor site without progression at registration
Progression of primary tumor site (breast, prostate, or lung) at time of registration
Patient must have a palpable, superficial tumor, safely accessible for bedside injection that will be radiated and can be accurately localized and stabilized if needed
Patients must have tumor (slides or block) available for submission for V600E BRAF testing
PD-L1 strong expressing tumor as determined by immunohistochemistry (IHC) at a central laboratory
Participants with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as HER2 positive
Known hormone receptor status of the primary tumor
Presence of an archived tumor sample (no size requirements)
Negative histologic margins of partial mastectomy or re-excision specimen; margins generally are positive if there is invasive or noninvasive tumor at the inked resection margin, close but negative if the tumor is within 2 mm of the inked margin and negative if the tumor is at least 2 mm away from the inked edge
Skin involvement, regardless of tumor size
Current or planned use of systemic therapy for extracranial primary tumor
Patients must have a tumor protein (p)53 mutation which is defined as cytoplasmic positivity by immunohistochemistry and/or next gene mutation sequencing
The subject has a primary brain tumor
The subject has tumor invading (or concern for invasion) major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Tumor in a location where enlargement could cause airway obstruction
Patients with skin metastases must agree to tumor fine-needle aspiration (FNA) required by protocol
Any \clinical\ T4 tumor as defined by primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer
Subject must undergo mandatory biopsies, including one pretreatment and one post treatment tumor biopsy procedure
CD30 positive tumor (result can be pending at this time)
CD30 positive tumor
Tumor in a location where enlargement could cause airway obstruction
Up to two (2) cancerous lesions may be identified in the prostate; each tumor is not more than 10 mm in maximal linear dimension; each tumor should comply with the maximal 7 Gleason score requirement.
Subjects with distance of the less than 2mm margin between the tumor and the prostate capsule
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
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
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
Must be willing and able to accept at least two tumor biopsies
RAS (KRAS and NRAS) wild-type in primary or metastatic tumor tissue
Availability of archived or representative tumor material for assessment of DLL3 expression
Pathology: representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 30 unstained slides); patients with < 30 slides may be enrolled after discussion with the principal investigator
Patients enrolled in the expansion stages must agree to a tumor biopsy to be obtained during the screening period and during Cycle 2 or at the time of PD, if earlier. If a biopsy is deemed by the investigator to not be in the patient's best interest, prior approval must be obtained from the Medical Monitor to waive this requirement.
Patient must have a site of disease for biopsy, and be a candidate for tumor biopsy according to the institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and again during therapy on this study.
Confirmation of the availability of a tumor sample from the primary or recurrent cancer must be provided
METex14 skipping alterations, as determined by the central laboratory (plasma and/or tumor biopsy sample)
Have a tumor genomic profile for which single agent treatment with one of the FDA approved targeted anti-cancer drugs included in this study has potential clinical benefit based on the criteria described in protocol
Meets Milan criteria: a single tumor that is < 5 cm or a maximum of 3 tumors with each tumor < 3 cm AND/OR meets UCSF criteria: a single tumor that is < 6.5 cm in diameter or 2 lesions < 4.5 cm with total tumor diameter < 8 cm AND/OR is outside of both Milan and UCSF criteria and is being evaluated for downstaging
Patient must agree to testing of GBM tumor promoter methylation status of the MGMT gene and tumor (IDH1) gene mutation status. Tissue may be tested at study entry, if not done previously, or data may be obtained from last known test result for MGMT and IDH1. IDH1 status may be assessed at study entry, but MGMT status is required prior to randomization.
Presence of punctate hemorrhage in the tumor.
Tumor cell programmed death-ligand 1 (PD-L1) score of tumor cells (TC)1-3 and immune cell PD-L1 score of tumor-infiltrating immune cells (IC)0-3 as determined by an immunohistochemistry (IHC) assay performed by the central laboratory on tissue obtained after the last line of therapy
Willingness to undergo a tumor biopsy
Patients must agree to pretreatment tumor biopsy
Cancer Tumor Size: T4
Have radiographic evidence of pulmonary intratumor cavitation, regardless of tumor histology.
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
Patient must have at least one and up to three asymptomatic metastatic tumor(s) of the bone or soft tissue develop within the past 6-months that are =< 5.0 cm or < 250 cm^3
Histologic confirmation of malignancy (primary or metastatic tumor)
Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (for nonsquamous NSCLC) or mRECIST (for epithelial pleural mesothelioma). Subjects with resected primary tumors who have documented metastases are eligible.
Surgically eligible for tumor resection with curative intent
Willing to attempt a baseline tumor biopsy procedure
Urethral tumor (prostatic urethra included).
Any invasive bladder tumor known to be other than tumor Ta, G1-G2.
Any bladder tumor with histology other than TCC.
Patient has a tumor in a bladder diverticulum.
For patients with recurrent tumor, the patient had at least a 6-month cystoscopically-confirmed tumor-free interval between the last tumor recurrence and screening cystoscopic examination.
Intact primary tumor (for Immune Response Cohort only)
Inability to undergo two sequential EUS-directed core biopsies of the primary tumor (for Immune Response Cohort only)
Tumor must have a supratentorial component
Any patient that has had a biopsy only or less than 25% of their tumor removed
All patients must undergo a baseline tumor biopsy for programmed cell death ligand 1 (PD-L1) testing (PD-L1 positivity is determined by greater than or equal to 1% of cells staining in the membrane by immunohistochemistry); for patients with stage IV disease, site of tumor biopsy will preferably be from non-lymph node disease site; the 28-8 clone for PD-L1 testing is required for assessment of PD-L1 status; for PD-L1 testing, the biopsy should contain sufficient tumor content (>= 100 tumor cells/4-micron tissue section); if a sample contains insufficient tumor content, a re-biopsy will be required to obtain a sample with sufficient tumor content prior to treatment
Primary tumor resected
At least one measurable tumor accessible for intratumoral injection and EP on investigator’s assessment
One of the following:\r\n* Upfront resectable disease; this is defined as:\r\n** No arterial tumor contact (celiac axis [CA], superior mesenteric artery [SMA], or common hepatic artery [CHA]); AND\r\n** No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV), or =< 180 degree contact without vein contour irregularity\r\n* Borderline resectable disease; There are multiple definitions of borderline resectable PDAC including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract; borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612); per this trial, borderline resectable PDAC is defined as the presence of any one or more of the following on CT or MRI:\r\n** An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring >= 180 degrees of the circumference of the vessel wall\r\n** Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction\r\n** Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction\r\n** An interface between the tumor and SMA measuring < 180 degrees of the circumference of the vessel wall
Centrally confirmed T790M mutation positive tumor status from a tumor sample taken after confirmation of disease progression on the most recent anticancer treatment regimen
Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma per pre-treatment biopsies by laparoscopy, or interventional radiology or CT guided core biopsy. Histologic documentation of the original primary tumor is required via the pathology report.
Patient must have adequate tumor specimen available for submission
Documented survivin-positive tumor status
The patient must not have received any immunotherapy for their brain tumor
Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ treatment
Unicentric: patients with microscopic multifocality are eligible as long as the total pathologic tumor size is =< 2.5 cm
The final margins of the resected specimen must be histologically free of tumor
Pathologic tumor > 2.5 cm in size
Consent for tumor biopsies and blood draws for research purposes
Histologic documentation of the original primary tumor.
Primary brain tumor
All tumor removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy)\r\n* NOTE: management of axillary lymph nodes is up to the treating provider; however, all surgical margins should be clear of invasive cancer or DCIS (i.e., no tumor on ink); the local pathologist must document negative margins of resection in the pathology report; if all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed; likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed
ELIGIBILITY FOR ENROLLMENT/SCREENING (ARMS 1 AND 2): Patients must be able to provide blood and tumor samples and undergo the procedures required for this protocol
ELIGIBILITY FOR TREATMENT ON ARM 1: Evidence of WT1 tumor expression
ELIGIBILITY FOR TREATMENT ON ARM 2: Evidence of WT1 tumor expression
Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
Consent to screening tumor biopsy (for accessible tumors when appropriate) (optional in dose escalation, mandatory in dose expansion)
Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology)
If the primary tumor had at least 50% clear cell histomorphology, a biopsy of the recurrent or persistent tumor is not required; the percentage of clear cell histomorphology must be documented in the pathology report or in an addendum to the original report; if slides of the primary tumor are not available for review due to disposal of slides by the histology laboratory (typically 10 years after diagnosis), biopsy of recurrent or persistent disease is required
If slides of the primary tumor are not available for review, a biopsy of the recurrent or persistent tumor is required to confirm at least 50% clear cell histomorphology; the percentage of involvement must be documented in the pathology report or in an addendum to the original report
All patients must submit unstained slides of primary or recurrent tumor for translational analysis
Patients must have measurable CNS disease, either previously untreated (not counting systemic therapy), or progressed following previous radiation treatment; lesions that have progressed after prior radiosurgery should not be selected as measurable disease if they are suspected of being radionecrosis; the following measurement criteria are required (not counting tumor edema, as visualized by contrast enhanced magnetic resonance imaging [MRI] with slice thickness of 1.5 mm or smaller, unless prospective permission is obtained from the principal investigator [PI] allowing absence of contrast or thicker slices): \r\n* At least one CNS tumor measuring 10 mm or greater in longest diameter, OR  \r\n* At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two additional CNS tumors measuring 3 mm or greater in longest diameter, for which the sum of the longest diameters is equal to or greater than 10 mm; patient may have additional tumors as well
Representative tumor specimens as specified by the protocol
A breast tumor with an ultrasound size of at least 2.0 cm.
RAS wild-type tumor; Note: evidence of EGFR expression in the tumor is not required
Availability of tumor sample:
Low risk for tumor lysis syndrome (TLS)
Tumor enhancement involving both hemispheres
Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor; residual tumor is required for enrollment on study
Patients acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator)
Subjects must consent to provide archived tumor specimens and / or tumor biopsy for correlative biomarker studies.
Documentation of HER2 overexpression or gene amplification, in the invasive component of either the primary tumor or metastatic disease site as defined as: 3+ by Immunohistochemistry (IHC) and/or
Agreement to provide 2 tumor biopsies
Tumor location or involvement that would result in risk of ventricular penetration during tumor injection
Tumor involving both hemispheres or that which involves the subependyma or suspected cerebrospinal fluid dissemination
Tumor involving brain stem
Subjects must have measurable disease defined as at least one tumor lesion of at least 1.5 cm or a peripheral blood cluster of differentiation (CD)5+, CD19+ lymphocyte count of at least 5,000 cells/uL
The patient has biopsy-accessible tumor; for patients who had no prior anticancer therapy and had surgical resection within a year and tumor tissue is immediately available, that tumor will be analyzed and no biopsy will be needed
Patients must agree to undergo two research biopsies of a malignant lesion; patients may be exempt from biopsy if 1) the investigator or person performing the biopsy judges that no tumor is accessible for biopsy, 2) the investigator or person performing the biopsy feels that the biopsy poses too great of a risk to the patient, or 3) the patient’s platelet count is < 100,000/mcl or he/she cannot be safely removed from anti-coagulation therapy (if the anti-coagulation therapy needs to be temporarily held for the biopsy procedure); if the only tumor accessible for biopsy is also the only lesion that can be used for RECIST v1.1 response evaluation, then the patient may be exempt from biopsy; the goal will be to have a minimum of 3 patients undergo one or both of these research biopsies; accrual may be limited only to subjects whose tumor is safely accessible for biopsy to ensure the accrual goal for research biopsies described above is met (e.g., if 7 of 10 patients are accrued without any biopsies having been obtained, then all subsequent subjects who are registered must qualify for attempted research biopsy in order to be enrolled)
Primary tumor greater than (>) 2 centimeters (cm) in diameter, or > 5 millimeters (mm) in diameter and node-positive
Participants who have had an incisional biopsy of the primary tumor or the primary tumor excised
Subjects with a current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas) are not eligible
Representative tumor specimens as specified by the protocol
Uncontrolled tumor-related pain
Measurable disease: subjects must have measurable plexiform neurofibroma(s) amenable to volumetric MRI analysis; for the purpose of this study, the target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest; tumors must be at least 3 mL in volume (most PNs 3 cm in longest diameter will meet this criteria); if the tumor is < 3 cm in longest diameter, the subject may still be eligible; central review of the MRI of the target plexiform is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis
Patients with malignant glioma, malignant peripheral nerve sheath tumor, or other malignancy requiring treatment in the last 12 months
Tumor not able to be reliably evaluated by volumetric analysis
AT THE TIME OF PROCUREMENT: EBV positive tumor
AT THE TIME OF INFUSION: EBV positive tumor
Evidence of histology of the tumor other than papillary serous adenocarcinoma or endometrioid type of endometrial carcinoma or mixed histology of the tumor;
Archived neuroendocrine tumor sample or biopsy sample (will also be used for genetic testing).
Histologically proven colon carcinoma with serosal invasion or peritoneal disease or a history of tumor rupture, and/or ascites
Patient should agree to a tumor biopsy prior to protocol enrollment; post therapy biopsy is optional
Have biomarker-positive solid tumor
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Patients with a history of malignant tumor who have been disease free for at least five years and are not currently being treated.
Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens
PD-L1-positive tumor status as determined by an immunohistochemistry (IHC) assay based on PD-L1 expression on tumor infiltrating immune cells and/or tumor cells performed by a central laboratory
Participants enrolled to the RP2D cohort must have disease that is accessible for tumor biopsies and must agree to pre and on-treatment tumor biopsies
Patients must have histological confirmation of a brain tumor at diagnosis or relapse for all tumors
Previously untreated participants are eligible if their tumor(s) are measurable
The cancer can be biopsied (depending on the tumor type and/or the dose of drug received, tumor biopsies may be required)
Metastatic breast cancer and have formalin-fixed, paraffin–embedded primary tumor available for testing BRCA1 protein expression
Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:
Prior use of other investigational agents to treat the brain tumor
Able and willing to give valid written consent for archival tumor samples
Known hormone receptor status of the primary tumor
Any clinical T4 tumor as defined by tumor-node-metastasis classification in UICC/AJCC 7th edition, including inflammatory breast cancer
Patients must have evidence of radiographic progression as defined below:\r\n* 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\r\n* Stratum 2: \r\n** 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\r\n** 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
The tumor tissue must have been determined to be KRAS, NRAS, BRAF, PIK3CA wild-type by central CLIA testing.
Targeted index tumor(s) defined as intra pulmonary or pleural with a maximum size of 3.5 cm, measured in the longest cross sectional dimension.
Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
Must have an FFPE tumor block with tumor cellularity of 20% or greater. NOTE: Prior to randomization, the tumor cellularity will be confirmed by central pathology review and percent values will be double checked at Paradigm (a Next Generation Sequencing Company).
Patients must have histologically proven stage IIIB, IV or recurrent non-small cell lung cancer; patients must be willing to undergo a pre-treatment tumor biopsy, either core needle biopsy or equivalent amount or via excisional specimen (cytology specimen not acceptable for this purpose)
Consent to preservation of frozen and fixed samples of tumor cores for evaluation
Patient with solid tumor malignancy with leptomeningeal metastases established radiographically and/or through CSF cytology.
Uncontrolled tumor-related pain
Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses
Has a locally determined non microsatellite instability high/ proficient mismatch repair (non-MSI-H/pMMR) tumor status
KIT-mutant tumor, including melanoma or gastrointestinal stromal tumor (GIST), for which there is no standard systemic therapy, or
Tumor is confirmed to be one of the following:\r\n* MSI-high, or\r\n* MMR-deficient, or\r\n* Hypermutated defined as >= 20 somatic mutations in the tumor by MSK-IMPACT
Submission of research blood draw to be stored until after surgical resection of the primary tumor and confirmation of human papilloma virus (HPV) positivity (Mayo Clinic Rochester patients only)
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in grade 2 or higher dyspnea at rest
Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization
Tumor replacement > 70% of total liver volume based on visual estimation by the investigator OR tumor replacement > 50% of total liver volume in the presence of albumin < 3 mg/dL
Patients must have a diagnosis and documented disease progression of a solid tumor malignancy, excluding primary brain tumor, for which standard, curative, or life prolonging treatment does not exist or is no longer effective
Patients must have radiographically or clinically evaluable tumor
All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy), with either a sentinel node biopsy or axillary dissection\r\n* All margins should be clear of invasive cancer or DCIS (i.e. no tumor on ink); the local pathologist must document negative margins of resection in the pathology report; if all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed; likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed; radiation therapy to the conserved breast is required
The patient must be discussed at GI Tumor Board, NCI and suitability for the interventional procedure (TACE or RFA) re-affirmed
There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per Response Assessment in Neuro-Oncology (RANO) criteria; when the interval is less than 12 weeks from the completion of radiotherapy, the use of positron emission tomography (PET) scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudo progression
Candidate for MLA based on the size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon
Low- or intermediate-grade neuroendocrine carcinoma, including the following subtypes: carcinoid tumor, low- to intermediate-grade or well- to moderately-differentiated neuroendocrine carcinoma or tumor, atypical carcinoid tumor; documentation from a primary tumor or metastatic site is sufficient; patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid tumor, or goblet cell carcinoid tumor are not eligible
Patients must have histologic documentation or clinical evidence of a carcinoid tumor of primary site (including foregut, midgut, hindgut or other non-pancreatic site); tumors of unknown primary site are eligible provided the treating physician does not suspect medullary thyroid cancer, pancreatic neuroendocrine tumor, paraganglioma, or pheochromocytoma; unknown primary tumors will be classified as small bowel tumors for the purpose of stratification; functional (associated with a clinical syndrome) or nonfunctional tumors are allowed; target lesions must have shown disease progression if therapy included peptide receptor radiotherapy (PRRT) and PRRT must be completed at least 8 weeks prior to registration
Tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall.
No available tumor material for correlative studies
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
Histologically confirmed definitive GBM or gliosarcoma by partial or complete surgical resection (i.e. not by biopsy only) within 5 weeks prior to PLX3397 administration (C1D1). Tumor must have a supratentorial component. For all patients, availability of a surgical paraffin tumor block sufficient to generate at least 20 unstained slides; or, if a paraffin tumor block is unavailable, at least 20 unstained slides.
Patients must have a K-RAS wild-type (WT) tumor
Histologic documentation of well differentiated or moderately differentiated locally unresectable or metastatic pancreatic neuroendocrine tumor from either a primary or metastatic site with documented disease progression =< 12 months prior to enrollment with whose disease is not currently amenable to surgery, radiation or modality therapy with curative intent; if different histologic classification schemes are used, equivalent histologic classifications (for example “grade 1,” “low grade,” or “intermediate grade”) are allowed; there must be histologic documentation of a pancreatic primary site or clinical evidence of a pancreatic neuroendocrine primary tumor as determined by the treating physician; documentation from a metastatic site is sufficient if there is clinical evidence of a pancreatic primary site; in the case of discordant pathology, patient eligibility will be determined by the principal investigator (PI) after review of available records; patients with neuroendocrine tumors (e.g., gastrinoma, vasoactive intestinal peptidase [VIPoma]) in whom a pancreatic or peripancreatic primary site is strongly suspected are also eligible
Cystic component >= 25% the total volume of the tumor
Subjects must have a target VS with the following qualities:\r\n* Not amenable to surgery due to patient refusal, high risk for surgical complications (e.g., damage to lower cranial nerve function, tumor size > 3 cm in longest diameter, or multilobulated tumor appearance on MRI scan)\r\n* Associated with a word recognition score of < 85% and > 5%\r\n* Documented clinical progression defined as EITHER:\r\n** Progressive hearing loss (defined as a decline in word recognition score below the 95% critical difference interval from baseline score related to VS (i.e., not due to prior interventions such as surgery or radiation) OR\r\n** Progressive tumor growth in the preceding 18 months, defined as >= 20% increase in volume
Presence of NRAS Q61 mutation in tumor tissue prior to randomization as determined by a Novartis designated central laboratory
Tumor of the patient is p53wt
Histologically proven solid tumor malignancy with metastasis to the spine; diagnosis may be acquired from needle biopsy, cytology, or surgical biopsy or resection
Primary tumors must be >= 5 cm in maximal diameter or an isolated local recurrence of any size; magnetic resonance imaging (MRI) or computed tomography (CT) of the primary tumor will be required; tumor size will be measured radiographically using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee; the tumor size will be accurately measured in at least one dimension and the largest diameter will be recorded in decimal fractions of centimeters
Recurrent or persistent tumor greater than 6 cm in maximum diameter
Patient’s tumor(s) to be treated is (are) =< 5.0 cm or =< 250 cm^3
Histological confirmation of malignancy (primary or metastatic tumor)
STEP 1 ENROLLMENT: the patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration; mixed tumors will be categorized by the predominant cell type
STEP 2 ENROLLMENT AND RANDOMIZATION: the patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration; mixed tumors will be categorized by the predominant cell type
Presence of BRAF mutation or genes fusion involving BRAF in tumor tissue
Pre-treatment fresh core, excision or punch tumor biopsy
Patient must not have transoral robotic surgery (TORS) for a T3 or T4 primary tumor
The subject has tumor invading (or there is concern for invasion of) major blood vessel
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Cohorts 1 and 2: In addition, patients have to meet one of the following high risk conditions: \r\n* Age >= 40 with any extent resection \r\n* Age 16-39 with incomplete resection (post-op MRI showing > 1 cm residual disease, based on the maximum dimension of residual T2 or fluid-attenuated inversion recovery [FLAIR] abnormality from the edge of the surgical cavity either laterally, anteroposteriorly, or superoinferiorly)\r\n* Age 16-39 with neurosurgeon-defined gross total resection (GTR) but the tumor size is >= 4 cm (the maximum preoperative tumor diameter, based on the axial and/or coronal T2 or FLAIR magnetic resonance [MR] images)
Patients must have a tumor site amenable to biopsy as determined by the treating investigator; any questions regarding suitability of a site for biopsy will be adjudicated by the principal investigator
Patients must have either (1) a diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the Memorial Sloan Kettering Cancer Center [MSKCC] Department of Pathology) or bone marrow (BM) metastases plus high urine catecholamine levels, or (2) a tumor that is GD2-positive\r\n* A non-NB tumor is defined as GD2-positive by immunostaining with monoclonal antibody 3F8 (m3F8); if fresh or frozen tumor is not available for immunostaining, patients will be considered eligible if published reports show that > 50% of that tumor type is GD2-positive by immunohistochemistry; (note: tissues must be fresh/frozen as fixed, paraffin-embedded specimens are unsuitable for anti-GD2 immunostaining); tumors known to be GD2-positive by this criteria do not need immunostaining; these include: melanoma (> 50%), desmoplastic small round cell tumors (70%), osteosarcoma (88%) and soft tissue sarcomas including liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma (93%)
Resectable primary tumor of the head, body or tail of the pancreas defined as a visible mass in the pancreas and:
A definable tissue plane between the tumor and regional arterial structures including the celiac axis, common hepatic artery, and SMA.
Documented cluster of differentiation (CD)30+ expression from either original diagnosis or a tumor biopsy in the relapsed setting
Tumor assayed for k-ras and other tumor genomic mutations
All patients must have progressive disease for which craniotomy and tumor resection is recommended as treatment
Patients with infratentorial, multifocal, or pathologically confirmed cerebrospinal fluid (CSF) disseminated tumor
Patients with a history of obstructive jaundice due to the primary tumor must have a metal biliary stent in place (or a percutaneous biliary drain)
Tumor/vertebral body anatomy precluding fiducial placement
Patients with tumor amenable to potentially curative therapy
Patients who are deemed \borderline resectable\ will be included; borderline resectable is defined by the NCCN as tumors with venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection or reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; or tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall; tumors involving retroperitoneal structures that can be surgically removed (ie. kidney), will also be included
Tumor specimen must be available for a central pathology review and prognostic and predictive biomarker evaluation
Patients with more than 30% replacement of hepatic parenchyma by tumor or any history of drug related hepatic encephalopathy
Patient's tumor must be positive by histological assay for NY-ESO-1?²??T, according to the screening algorithm as described in Section 3.3.1. Positive expression is defined as ? 50% of cells that are 2+ and/or 3+ by immunohistochemistry
Patients with diffuse tumor throughout bladder that is deemed unresectable by surgeon
Only untreated patients with high risk pancreatic adenocarcinomas will be eligible for the study; for this study, such patients are defined as those who meet one or more of the following radiographic or serologic criteria:\r\n* Primary tumor that involves the superior mesenteric vein causing a vein deformity or segmental venous occlusion with a patent vessel above and below suitable for reconstruction\r\n* Primary tumor that involves =< 180 degrees of the superior mesenteric artery (SMA), celiac axis or any of its branches on CT or magnetic resonance imaging (MRI)\r\n* Primary tumor that abuts or encases (>= 50% of the vessel circumference) a short segment of the common hepatic artery (typically at the gastroduodenal artery origin)\r\n* Patients with a high cancer antigen 19-9 (CA19-9) (>= 500 mg/dl) in the presence of a bilirubin =< 2.0 mg/dL\r\n* Radiographic findings consistent with malignant peripancreatic lymphadenopathy outside the planned field on CT or MRI\r\n* Radiographic findings of indeterminate liver or peritoneal lesions on CT or MRI concerning but not diagnostic of metastatic disease
Histologic confirmation of prostatic adenocarcinoma by Memorial Sloan Kettering Cancer Center (MSKCC) inclusive of the following:\r\n* 3 or more positive biopsy cores or equivalent tumor specimen as confirmed by pathologist\r\n* At least 2 cores containing >= 3 mm of tissue with carcinoma or equivalent tumor specimen as confirmed by pathologist\r\n* A primary tumor Gleason score >= 7\r\n* Adequate primary biopsy tissue or equivalent tumor specimen as confirmed by pathologist available for protocol required analysis (i.e., bladder or transurethral resection of the prostate [TURP] specimen)
Histologic variants in the primary tumor (histologic variants other than adenocarcinoma)
Biopsy accessible tumor deposits
Tumor cell negative for CD20
Patients to be scheduled for a planned tumor debulking
Evidence of laboratory tumor lysis syndrome (TLS) by Cairo-Bishop definition of tumor lysis syndrome; subjects may be enrolled upon correction of electrolyte abnormalities
Invasive primary tumor or metastatic tissue confirmation of HER2-positive status, defined as presence of one or more of the following criteria
At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis
HER2-positive as assessed by local laboratory on primary or metastatic tumor
No prior chemoradiation to the primary pancreatic tumor unless there is a measurable distant site of disease
Tumor is well visualized through x-ray mammography or ultrasound imaging and amenable to image guidance therapy (a tumor which is well visualized through imaging can be identified from surrounding breast tissue and does not have margins
Unifocal malignant tumor that does not exceed 20mm in diameter and measures at least 5mm away from the skin and chest wall
Subjects with mammographic appearance of overall dense parenchymal tissue may be included, as long as a clearly evident marker is present at tumor site
Subjects with benign vascular tumor
Patients must have recurrent or metastatic tumor located within a previously irradiated field
Tumor within the irradiated field is negatively impacting patient’s quality of life or threatening catastrophic complication if left untreated as determined by the treating physician
Tumor sites eligible for inclusion on this protocol include thorax, abdomen, and pelvis
Diagnosis of DIPG by MRI imaging defined as tumor that has a pontine epicenter and is diffuse (tumor that involves the majority [> 50%] of the brainstem) on T2 or fluid-attenuated inversion-recovery (FLAIR) imaging rather than focal; histologic confirmation is not required
At least one measurable VHL related lesion, which is undergoing surveillance, and patient is not at immediate risk of needing intervention for this or other lesions; biopsy is not required given the known likely etiology and natural history in the setting of a positive genetic test\r\n* Brain: asymptomatic hemangioblastoma, >= 0.5 cm\r\n* Spine: asymptomatic hemangioblastoma, >= 0.5 cm\r\n* Renal: solid mass suspicious for renal cell carcinoma (RCC) >= 1 cm or cystic mass (Bosniak 3-4) >= 1 cm\r\n* Pancreas: solid mass >= 1 cm and =< 3 cm suspicious for neuroendocrine tumor, or neuroendocrine tumor > 3 cm but not considered operable\r\n* Eye: asymptomatic peripapillary and/or macular hemangioblastoma, any size\r\n* Adrenal: asymptomatic or controlled pheochromocytoma greater than 1 cm in size
Consent to biopsy of tumor
Longest uni-dimensional measurement of contrast enhancing tumor >= 4 cm; tumors exceeding this limit may be eligible and any question should be directed to a radiation oncology investigator and the MSK PI
Tumor must not invade the corpus callosum
Tumor must not invade the brainstem
Patients must have a biopsy confirmed diagnosis based on a combination of histological and clinical criteria of CD30+ lymphomatoid papulosis, CD30+ primary cutaneous anaplastic large T-cell lymphoma (pc-ALCL), or CD30+ mycosis fungoides for the phase II trial; there is no specific limit or validated amount other than positive cells on immunohistochemistry (IHC) cells in tumor cells
Evidence of brainstem/cord/cauda or other neuromuscular or neurosensory malfunction from causes other than effects of local tumor growth or metabolic effects of tumor
Gross extension of tumor into the lumen of the duodenum
Tumor must express Retinoblastoma (Rb) protein, as defined as any measureable staining by immunohistochemistry
Unwilling to provide consent for genetic studies of tumor, whole blood, or plasma specimens
Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
Willingness to undergo tumor biopsy
The subject has biopsy accessible tumor and is willing to undergo biopsy prior to planned protocol treatment
Patients must have an intact primary (not recurrent) invasive carcinoma of the breast; biopsy confirmation of the primary tumor should be by needle biopsy (preferred); incisional surgical biopsy is allowed as long as there is residual palpable or imageable tumor in the breast
* Primary tumor progression on first-line chemotherapy
Known endobronchial lesions or involvement of large pulmonary vessels by tumor
EXPANSION COHORT ONLY: Known endobronchial lesions or involvement of large pulmonary vessels by tumor
Extensive (invasive) loco-regional tumor mass and/or metastatic spread, rendering patient inoperable
Patients must be willing to forego other drug therapy against the tumor while being treated with bevacizumab and temozolomide
Subject for whom tumor lysate does not meet release criteria
The tumor must be supratentorial in location
The planning target volume (PTV), defined as residual T1 post-contrast enhancing tumor and/or resection cavity plus 0.5 cm margin, must measure =< 150 cm^3 in volume; this volume will not be known at the initial consultation; it will be determined once the final radiation plan is completed
Tumor foci detected below the tentorium
A solid tumor diagnosis in the setting of:
Evidence of measurable disease either by RECIST 1.1 or elevation of serum tumor markers (AFP > 15 ng/mL or HCG > 2.2 mIU/ml)
Tumor size of at least 5 centimeters
Pathologic T stage of Tis, T1, or T2 with total size of tumor =< 3 cm (this size criteria applies to both pure ductal carcinoma in situ [DCIS] and invasive tumors)
Unifocal primary tumor based on imaging and clinical assessment; microscopic multifocality is allowed
Tumor invasion of the skin including dermis, chest wall, or pectoralis musculature
Confirmed RAS/RAF wild type tumor; paraffin-embedded tumor tissue obtained from the primary tumor or metastasis
a) Dose Evaluation Portion: Patients should have at least one lesion accessible for intratumoral injection and biopsy. b) Melanoma Expansion Cohort: Patients must have at least one target lesion by Response Evaluation Criteria for Solid Tumors (RECIST v1.1), with at least one lesion accessible for intratumoral injection. Tumor biopsies are not required in the expansion cohort.
Provides a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory.
Close (<3mm) or positive surgical margins on microscopic evaluation with no gross residual tumor
High Tumor Mutation Burden
Histological confirmation of malignancy (primary or metastatic tumor)
(continued from no. 1) Those patients with stage III cancer in which the largest maximal diameter of any residual tumor implant at the completion of this initial surgery is no greater than 1 cm will be defined as optimal; all others will be defined as suboptimal.
Tumor positive for infection with human papillomavirus (HPV) virus type 16 or other types such as per Johns Hopkins (JH) Pathology assessment
T stage 1, 2, 3; surgery of the primary tumor is limited to incisional or excisional biopsies (i.e., tonsillectomy) even without macroscopic disease left; positive resection margins and/or gross residual disease at the primary site are allowed; evaluation of primary tumor extent may require the use of a flexible fibroscope if deemed clinically necessary by the treating physician
Oropharyngeal sites of tumor include tonsil, soft palate, base of tongue, lateral and posterior pharyngeal wall; laryngeal sites of tumor include the supraglottic, glottis and subglottic larynx; nasopharyngeal sites include the posterior nasopharyngeal wall, right and left fossa of Rosenmuller; the hypopharyngeal sites of tumor include the post-cricoid area, posterior pharyngeal wall and the pyriform sinuses
There must be documentation of evaluable tumor within four weeks of beginning therapy
Diagnosis of primary brain tumor
Participants must have histologically confirmed germ cell tumor or elevated alpha-fetoprotein (AFP) (serum > 10 IU/L or cerebrospinal fluid [CSF] > than institutional norm) or beta-human chorionic gonadotropin (B-HCG) (serum or CSF > than institutional norm) in the setting of radiographic disease consistent with a germ cell tumor; disease must be confined to the central nervous system
The tumor should be approximately at least 1 cm, to account for variability in imaging and imaging occult disease (physical exam, mammography, ultrasound); we recognize that from time to time because of this variation, there might not be enough tissue available for analysis after surgical excision but this will allow the greatest opportunity to capture as many eligible patients as possible
Optional: Willing to provide a fresh tumor sample if a sufficient quantity of archival tumor sample is not available (Arms B, C, and D). See Section 5.3.9 for tumor sample details.
Patients must have paraffin-embedded tumor specimen available for submission for pathological review and determination of 1p/19q deletion status\r\n* NOTE: it is recommended that patients not be pre-registered until the required tumor specimens are on hand and ready for submission; if submission of tissue will be submitted more than 5 working days after pre-registration, immediately notify the Mayo Clinic Cytogenetics Laboratory via email
No previous radiation, cytotoxic chemotherapy, radio surgery, or investigational treatment directed at the brain tumor at any time; no limit on number of previous surgical procedures of this tumor
Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression
MGMT promoter methylation analysis of surgically resected tumor or tumor biopsy must demonstrate an unmethylated or hypomethylated MGMT promoter status
Methylated or hypermethylated MGMT promoter status within tumor tissue
Tumor must be accessible for injection and must not be located in the brainstem or deep midbrain
No other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from study entry until tumor progression)
Prior surgery for a low grade tumor is allowed, provided histological confirmation of anaplastic tumor is present at the time of progression
Tumor size greater than 4 cm;
Gross total resection as determined by the intraoperative observations of the neurosurgeon of record and confirmed by postoperative MR imaging; gross total resection is defined as residual tumor or imaging abnormality (not definitive for residual tumor) whose size is < 1 cm^2 on postoperative computed tomography (CT) or MR images
If there is brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size < 1 cm^2) and the patient otherwise meets criteria for enrollment on the low-risk arm, the patient will be classified as low-risk
Patients who have undergone recent resection of recurrent or progressive tumor will be eligible as long as they have recovered from the effects of surgery. Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual measurable disease post-operatively, a MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively.
Group B: Radical resection of tumor, which may necessitate major bone or soft tissue reconstruction.
Massive tumor (> 20 cm in greatest dimension)
Amputation of the affected leg as treatment of tumor
Patients must have a histologically confirmed diagnosis of a malignancy known to express GD2; such tumors include medulloblastoma/primitive neuroectodermal tumor of the central nervous system (CNS), high grade astrocytomas, malignant glioma, neuroblastoma, retinoblastoma, ependymoma, rhabdoid tumors, sarcomas, melanoma or small cell lung carcinoma; for patients with other tumor types, GD2 expression must be confirmed by immunohistochemical staining and assessed by the Department of Pathology using prior frozen tissue, bone marrow or cerebrospinal fluid (CSF) cytology
Patients must have CNS/ leptomeningeal disease including high risk medulloblastoma, or a CNS/leptomeningeal malignancy which is refractory to conventional therapies, or for which no conventional therapy exists, OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, primitive neuroectodermal tumor [PNET], rhabdoid tumor)
History of malignant peripheral nerve sheath tumor
At least 42 days must have elapsed after the completion of any type of immunotherapy, e.g. tumor vaccines
Availability of an adequate archival tumor specimen or willingness to undergo a pretreatment tumor biopsy.
Subjects enrolled in Expansion Cohort 3 must be willing to have 2 on-treatment tumor biopsies.
Vessels providing flow to the tumor that are less than 1.5 mm in diameter.
Subjects must have evidence of recurrent or metastatic carcinoma by one or more of the following:\r\n* The appearance of metastatic disease on chest x-ray or computed tomography (CT) scan\r\n* The appearance of rising tumor marker: AFP or beta-human chorionic gonadotropin (HCG)\r\nNOTE: if a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least one week apart are needed; subjects with only evidence of disease as rising tumor marker AFP and beta-HCG will be assessed for alternate causes of increased serum levels of these markers, such as cross reaction with luteinizing hormone (LH) (can be tested if needed by testosterone suppression of LH), hepatitis, use of marijuana, or second primary tumor
“Failure” of prior therapy is defined as:\r\n* A > 25% increase in the products of perpendicular diameters of measurable tumor masses during prior therapy which are not amenable to surgical resection\r\n* The presence of new tumors which are not amenable to surgical resection\r\n* An increase in AFP or beta-hCG (two separate determinations at least one week apart are required if rising tumor markers are the only evidence of failure)\r\nNOTE: subjects with clinically growing “teratoma” (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery
For Expansion Cohorts only: patients must have tumor accessible for biopsies (core needle biopsy or excision preferred).
Participants must have available archival or fresh tumor tissue or both to submit to a central laboratory for CD38 assay. Expression of CD38 is measured by immunohistochemistry on fresh or archived tumor sample by central assessment using a CD38 investigational IHC assay under development: a) Stage 1: participants whose tumors are more than or equal to (>=) 50 percent (%) positive for CD38, b) Stage 2: participant has less than (<) 50% CD38+ or greater than (>) 50% CD38+ depending on the distribution of CD 38 expression of enrolled participants during Stage 2. The sponsor will advise on which eligibility criterion is permitted during the enrollment period
Has ability to submit archived or fresh tumor sample during the screening period
Pathologically documented diagnosis of advanced solid tumor malignancy that progressed after appropriate prior therapy or has no potential for cure with currently available treatments.
Patient must have persistent or recurrent high grade endometrioid or serous ovarian, primary peritoneal or fallopian tube carcinoma; histologic documentation of the original primary tumor is required via the pathology report
For subjects receiving adjuvant therapy only, subjects must have undergone complete resection of the primary tumor with clean surgical margins, or subjects must have undergone resection of the primary tumor and be scheduled for further treatment of the primary tumor with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization
Tumor sample is available for retrospective CDH6 expression testing
Ineligible for curative resection or for liver transplantation according to the Milan criteria (single tumor =< 5 cm in size or =< 3 tumors each =< 3 cm in size) or the downstaging criteria already established
FDG avid malignancy\r\n* Patients must have an FDG avid tumor(s)\r\n* FDG avid tumors are defined as a primary tumor with an increased uptake in the region of the tumor that has an SUV of > 5.0 or a tumor:liver SUV ratio of > 1.5
Prior treatment with panitumumab for subjects with KRAS and NRAS wt tumor
Prior intolerance to fluoropyrimidine for subjects with KRAS or NRAS mut tumor
Subject must have a pathologically documented, definitively diagnosed, advanced solid tumor
Accessible tumor that can be biopsied at acceptable clinical risk (as judged by the investigator) and must consent to pre-treatment and on-treatment tumor biopsies; tumor biopsy sites need not be distinct from evaluable lesions but must not have been irradiated prior to study entry
Tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall.
For Phase 2, has archived or fresh tumor biopsy samples (obtained during screening) sufficient for genotyping.
History of symptomatic metastatic brain or meningeal tumors unless the subject is longer than 3 months from the end of definitive therapy before the first dose of the investigational drug and has clinically or radiologically no evidence of tumor growth.
Cohort Expansion: Subjects must be determined to be HA-high based on tumor biopsy that meets the requirements noted in the previous inclusion criterion.
Patients must have at least one tumor accessible for intratumoral injection and EP on investigator's assessment.
Willingness to consent to the use of baseline diagnostic tumor specimen for correlative studies (any diagnostic material will be acceptable- paraffin block, cell block, fine needle aspirate etc.)
Tumor foci below the tentorium or beyond the cranial vault.
The cancer can be biopsied (depending on the tumor type and/or the dose of drug received, tumor biopsies may be required)
c-MET positive (defined by c-MET IHC intensity score +2 in ? 50% of tumor cells and MET gene copy number ? 5 by FISH or IHC intensity score +3 in ? 50% of tumor cells) and K/NRAS WT status for mCRC patients only
After a restaging transurethral resection of bladder tumor (TURBT), patients with histologically proven primary high grade and/or pT1 transitional cell carcinoma of the bladder, with or without pTis and pTis alone are regarded as being at high risk for tumor recurrence and progression
Direct tumor extension into the stomach, duodenum, small bowel or large bowel
Patients must show signs of progression (by imaging, or tumor marker elevation) after being treated with a first line or greater treatment for their un-resectable or metastatic colorectal cancer
Willingness to undergo leukapheresis and biopsy procedures for the autologous components (peripheral blood mononuclear cells, plasma and fresh tumor specimen) required for manufacture of AGS-003
Participants must have a confirmed or suspected invasive or non-invasive bladder tumor (initial or recurrent) discovered on cystoscopy or radiologic imaging performed within 120 days of randomization
Participants must be a candidate for a trans-urethral resection of the bladder tumor (TURBT), cystectomy (partial or radical) or cystoscopy with biopsy at a participating organization
Any treatment for the bladder tumor other than intravesical therapy between the pre-study cystoscopy or radiologic imaging which identified the suspected bladder tumor and the scheduled surgical removal or cystoscopy-guided biopsy of that tumor
Histologic variants other than adenocarcinoma in the primary tumor
A tumor lesion that can be safely biopsied as judged by the treating oncologist and physician performing the procedure and has not been radiated
Coagulopathy or anticoagulation therapy that cannot be safely corrected or interrupted for tumor biopsy
The primary tumor must be in a location amendable to RFA within the kidney
There are no limitations based on location of the primary tumor within the kidney
Tumor without activating driver mutations for which there is available therapy (eg, tumor without mutations in epidermal growth factor receptor or anaplastic lymphoma).
Assessment by the attending thoracic surgeon that the primary tumor is resectable in pts with NSCLC and pleural spread; tumor will be deemed resectable if there is no extension through fascia, no bony chest or vertebral body involvement, and no radiographic evidence of mediastinal involvement
Tumor accessible for unrestricted illumination for interstitial photodynamic therapy (PDT) (accessibility as determined by the physician)
Tumor invading a major blood vessel (such as the carotid artery)
Location and extension of the tumor precludes an effective I-PDT
Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal dissemination, gliomatosis cerebri or infratentorial tumor
Diagnosis of an advanced solid tumor malignancy.
Patients must be amenable to receiving 1 dose of HSV1716 intra-operatively with planned HSV1716 injection sites >= 1 cm from the ventricular system AND meet at least one of the criteria below based upon pre-surgical magnetic resonance imaging (MRI):\r\n* Tumor is >= 1 cm from the ventricular system\r\n* Patients whose tumors that are =< 1 cm from the ventricular system are eligible if there is sufficient space within the tumor cavity and/or residual tumor to perform the HSV 1716 injections that are >= 1 cm from the ventricular system
Tumor MET amplified by protocol-specified centralized testing.
Currently receiving any anti-tumor treatments, or less than 14 days prior to enrollment since ending anti-tumor treatment
Clinical stage I-III invasive breast cancer with the intent to treat with surgical resection of the primary tumor; tumor must be >= 2 cm to provide adequate tissue
Tumor must not have been treated previously with radiation
Targeted tumor(s) are accessible to the ExAblate device
Patients in whom the targeted volume within the tumor is located deeper than 1 cm from the skin
Target volume in tumor is less than 1 cm from neurovascular bundles, major blood vessels, bowel or bladder
Preferentially radiologically by tumor growth or new lesions, or by
Tumor volume ? 70% of liver volume (determined by visual estimation)
INCLUSION CRITERIA:\n\n        Pre-Treatment Phase: Tissue Procurement and Establishment of Tumor Cell Line\n\n          1. Histologic diagnosis of invasive melanoma.\n\n          2. Measurable metastatic melanoma with at least one lesion amenable to -resection Stage\n             III: recurrent regional disease, including regional disease with no known primary.\n\n             Stage IV: distant metastatic melanoma.\n\n          3. Age 18 years and older.\n\n          4. Sign the \Tissue Consent\, the pre-Clinical Informed Consent for Melanoma Tissue\n             Procurement and initiation of cell line effort granting Caladrius permission to\n             cryopreserve the tumor and/or to initiate an autologous tumor cell line from excess\n             tissue that has been removed during a medical procedure (e.g., surgically excised).\n\n          5. Initiation of Autologous Tumor Cell Line. Caladrius must have received a viable\n             melanoma tumor tissue specimen that has been obtained and processed according to\n             company SOPs to ensure tissue viability. The cell line can be initiated with either a\n             specimen of fresh tumor or tumor that has been previously cryopreserved.\n\n        Treatment Phase\n\n          1. Successful establishment of an autologous melanoma cell line by Caladrius.\n\n          2. Patients with multiple depots of distant metastatic disease must have previously\n             received at least one or more of the following standard treatments: interleukin 2\n             (IL-2), or ipilimumab, or vemurafenib (if tumor expresses the V600E mutation), or\n             dacarbazine or temozolomide, if not mutated for the V600E mutation, and not felt to be\n             medically appropriate for IL-2 or ipilimumab. These may have been given alone, or in\n             combination with other agents.\n\n          3. Medical fitness to undergo a leukapheresis, including peripheral venous access or\n             access by central vein if necessary.\n\n          4. Medical fitness for participation in a phase III clinical trial.\n\n               -  a. ECOG performance status of 0 or 1.\n\n               -  b. Adequate bone marrow function: absolute neutrophil count (ANC) greater than\n                  1000/mm (3), hematocrit greater than 30%, platelet count greater than 100,000/mm\n                  (3), no ongoing transfusion requirements.\n\n               -  c. Adequate hepatic function: total bilirubin less than 2.0 mg/dL, alanine\n                  aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times the\n                  upper limit of normal (ULN), albumin greater than 3 g/dL.\n\n               -  d. Adequate kidney function: creatinine less than or equal to 2.0 mg/dL.\n\n               -  e. Negative pregnancy test for woman of childbearing potential and use of\n                  effective contraception (hormonal or barrier method of birth control) during\n                  therapy (women of childbearing potential and men).\n\n          5. Extent of disease established within 4 weeks of randomization.\n\n               -  a. History and Physical Exam by a licensed practitioner.\n\n               -  b. Fludeoxyglucose(FDG)-based PET/CT or PET scan and CT scan.\n\n               -  c. Brain MRI demonstrating no new untreated or uncontrolled metastases.\n\n          6. Recovery from previous therapies.\n\n               -  a. At least four weeks (28 days) must have elapsed since any prior systemic\n                  therapy at the time of the first dose (six weeks for anti-cytotoxic T\n                  lymphocyte-associated antigen 4 (anti-CTLA-4), and any toxicities experienced\n                  must have recovered to a grade 1 or less (except for alopecia or vitiligo).\n\n               -  b. More than three weeks (at least 22 days) since radiation therapy at the time\n                  of the first dose (7 days for single-dose stereotactic radiotherapy such as gamma\n                  knife) and recovery from acute toxicities. Patients treated with whole brain\n                  radiation must wait at least 22 days after completion of radiation and have\n                  radiographic confirmation of lack of progression before proceeding to\n                  randomization.\n\n        EXCLUSION CRITERIA:\n\n        Pre-Treatment Phase: Tissue Procurement and Establishment of Tumor Cell Line\n\n          1. Eastern Cooperative Oncology Group (ECOG) performance status greater than 2\n\n          2. Lack of a metastatic melanoma lesion that can be resected.\n\n        Treatment Phase\n\n          1. Known positive for hepatitis B or C or HIV.\n\n          2. Pregnant or lactating women.\n\n          3. Underlying cardiac disease associated with known myocardial dysfunction, or active\n             treatment with digoxin or other medications being given to treat heart failure, or\n             unstable angina related to atherosclerotic cardiovascular disease.\n\n          4. Diagnosis of any other invasive cancer that requires ongoing treatment or for which\n             there is evidence of active disease.\n\n          5. Active, unresolved infection and/or receiving concurrent treatment with parenteral\n             antibiotics (patients are eligible after antibiotics have been discontinued for at\n             least 7 days prior to first dose and evidence of infection has resolved).\n\n          6. Other active medical condition that could be imminently life threatening, in the\n             opinion of the investigator, including no active blood clotting or bleeding diathesis.\n\n          7. New or uncontrolled brain metastases or leptomeningeal disease and/or taking\n             pharmacological doses of corticosteroids. Brain metastases treated by gamma knife or\n             stereotactic radiotherapy are considered controlled, unless patient requires\n             pharmacologic doses of corticosteroids. It is recognized that tumor necrosis may be\n             confused with tumor progression in interpretation of Brain MRI.\n\n          8. Known autoimmune disease, immunodeficiency, or disease process that involves the use\n             of immunosuppressive therapy.\n\n          9. Taking other anticancer therapy.\n\n         10. Received another investigational drug within 28 days of the first dose.
Histologically confirmed diagnosis of glioblastoma (after initial tumor resection or biopsy) with radiographic evidence of recurrent tumor per RANO criteria.
Subjects must have at least one tumor lesion that is suitable for repeat biopsy, and must agree to two tumor biopsies (pre- and post- treatment).
Willingness to provide at least one pre-and post-vaccination tumor biopsy sample.
Patients must have disease that is potentially amenable to curative resection as reviewed by the Medical University of South Carolina (MUSC) Gastrointestinal (GI) Tumor Board
If the index tumor is in the spine, there must be an intact cortex between the mass and the spinal canal and exiting nerve roots
Index tumor involves the skull (treatment of other painful tumors in subjects with skull tumors is not excluded)
An untreated tumor growth rate of < 6.1% during the Screening period may exclude some patients.
Evidence of MCPyV TAg tumor expression
Tumor located in the supra-tentorial region of the brain
Tumor >= 0.5 cm from skin as defined by breast ultrasound
Unicentric tumor
Negative surgical margins, defined as no margin-labeling ink on tumor cells from margin evaluation
Patients with =< 10 cc largest tumor volume, and =< 15 cc total tumor volume
The subject has a primary brain tumor
The subject has tumor in contact with, invading or encasing major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Patient must have radiologic demonstration of stable disease or tumor response
Patients must have disease that is potentially amenable to curative resection as reviewed by the Medical University of South Carolina (MUSC) Gastrointestinal (GI) Tumor Board
Tumor foci below the tentorium or or beyond the cranial vault
At least 2 organs involved in metastatic gastric tumor (including at least lung or liver or both) in addition to the site of primary tumor, where metastasis in distant lymph nodes, peritoneal metastasis, and malignant pleural effusion may count as \organs\ in this context
HER2-positive primary or metastatic tumor as assessed by central laboratory
Tumor biopsy specimen with ? 50% of MUC1 expressing tumor cells determined by Immunohistochemistry (IHC) staining on fixed pathological material. Biopsy may come either from the primary tumor or from a metastasis. Cytological material is not accepted for this analysis
Patients with tumor amenable to potentially curative therapy as assessed by the investigator
Patients on stage 2 of the enrollment must have tumor sites that are easily biopsied and be willing to undergo pre- and post-treatment (around day 8 +/- 3 days) tumor biopsies
Patients with tumor amenable to potentially curative therapy as assessed by the investigator
For Part A, the subject has histological or cytological evidence of a solid tumor; for Part B, the subject has histological or cytological evidence of 1 of the following solid tumor types: melanoma, renal cell carcinoma, or ovarian cancer
Pancreatic tumor size =< 5 cm
Androgen receptor expression testing confirms that the patient’s tumor is AR (+); AR is considered positive if >= 1% of cell nuclei are immunoreactive using the Dako antibody (clone androgen receptor antibody [AR441]); receptor testing may be performed on either primary tumor specimen or tissue from a metastatic site; local testing permitted for eligibility but will require confirmation at Memorial Sloan-Kettering Cancer Center (MSKCC)
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:\r\n* 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
Tumor size 1 cm or greater; N any; M0 (Cohort 1)
Tumor size 2 cm or greater; N any; M0 (Cohort 2)
Subjects must consent to provide archived tumor specimens or tumor biopsies for correlative biomarker studies.
The subject has tumor invading any major blood vessels
The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Histopathologic confirmation of the following tumor types (please refer to protocol for full details pertaining to eligible tumor types):
Gastric or Gastro-Esophageal junction carcinoma (No longer enrolling this tumor type)
anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and
Patient has received an HSCT transplant for a solid tumor disease.
Consent to provide archived tumor specimens
The subject has a tumor suitable for biopsy and is willing to undergo tumor biopsy, preferably of the primary tumor, within 28 days prior to Cycle 1/Visit Day 1;
Diagnosis of an advanced solid tumor malignancy. There must be a target tumor which is measureable, palpable or clearly identifiable under ultrasound or radiographic guidance and amenable to percutaneous injection of C. novyi-NT spores. The targeted lesion must have a longest diameter ? 1 cm and ? 12 cm and be measurable as defined by RECIST 1.1 criteria. The target lesion must not be located in either the thoracic, abdominal or pelvic cavities or in the brain. There must be no clinical, no functional, and no radiographic evidence of bone involvement at the site of the target lesion.
Evidence of tumor invading major blood vessels, cavitation of one or more pulmonary tumor mass(es) ortracheo-esophageal fistula
Patients should have either non-metastatic cancer of the thorax, or metastatic cancer to the thorax and candidate for definitive radiation dose to the thoracic tumor (not palliative intent), tumor radiation dose to at least BED2Gy 60 Gy
Part A: Any type of solid tumor (\all comer\)
Availability of a tumor sample taken after progression on the most recent line of systemic tumor therapy or willing to undergo a tumor biopsy pre-study treatment.
Relapsed or progressive advanced solid tumor malignancies
At least 25% of cells >= 1+ for FRa staining based on diagnostic (i.e., prior to NAC) tumor biopsy
Ability to comply with the collection of tumor biopsies; tumors accessible for biopsy
Other concomitant anti-tumor therapy as determined by the study team.
Breast tumor ?1 centimeter (cm) in diameter, HR+, HER2-.
Uncontrolled tumor-related pain
If the subject received neoadjuvant therapy, residual tumor is present (to be determined by the primary surgeon)
Diagnosis of cervical cancer with a tumor size greater than 2 cm.
Sarcoma or Wilms tumor diagnosis (Group C) will require evaluation by physician in the St. Jude Solid Tumor Division, other than the referring physician, attesting that autologous stem cell transplant (SCT) provides the prospect of direct benefit for the participant
Anti-tumor therapy within 14 days of study day 1
Biopsy accessible tumor deposits
At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
HER2-positive tumor (primary tumor or metastatic lesion) as confirmed by central\n             laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)
Part 1 (enrollment closed): an advanced, incurable solid tumor
Part 2 (enrollment closed): an advanced, incurable solid tumor for whom a taxane would be considered a reasonable chemotherapy option
Primary tumor and any positive node(s)measurable in 2 dimensions
Prior resection of jugular nodes ipsilateral to tumor
Documentation of HER2 overexpression or gene amplification in the invasive component of either the primary tumor or metastatic disease site defined as:
Unwilling to allow removal of tumor biological samples for analysis, i.e., biopsies of tumor lesions, and/or collection of ascites fluid from abdominal ascites (if present)
Non epithelial tumor, including malignant mixed Müllerian tumors without high grade serous component, or ovarian tumors with low malignant potential (i.e., borderline tumors)
Symptomatic intrinsic lung disease or extensive tumor involvement in the lungs resulting in dyspnea at rest
Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification
Willingness to undergo two tumor biopsies: before and after administration of RO7070179.
Radiographic evidence of cavitating pulmonary lesions and tumor adjacent to or invading any large blood vessel unless approved by sponsor.
At least one tumor amenable to excisional, core or forceps (transbronchial) biopsy; patients must be willing to undergo tumor biopsies before starting therapy and after the third (3rd) CDX-1401 injection; additionally, the first 12 patients enrolled must consent to a third tumor biopsy to be performed after the 3rd MPDL3280A infusion
Intact breast tumor present and size measuring at least 1 cm at enrollment
Confirmation in a CLIA certified laboratory or in an FDA-approved assay that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V600.
Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
Anti-tumor therapy within 21 days of study Day 1
Primary tumor (osteogenic origin, etc.) at site.
One or more of the following “risk” criteria for failure with conventional SBRT treatment alone:\r\n* Peripheral tumor >= 4 cm in any dimension\r\n* Central tumor (i.e. gross tumor within 2 cm of a major bronchus/vessel, or heart/pericardium), including hilar lymph node(s)\r\n* Multiple tumors (i.e. satellitosis-defined T3-4, or bilateral synchronous primary lung cancer; note that the maximum number of total lesions allowable on this study for treatment with SBRT is 3 (three), and all lesions must be amenable to SBRT and treated with SBRT on this study; note that it is not necessary for all lesions felt to be malignant to be biopsied
Patients must express NY-ESO-1 in their tumor by immunohistochemistry (IHC) (> 5%) prior to leukapheresis
Patient must have a biopsy-accessible tumor to be radiated
Subjects with a neuroendocrine tumor of the pancreas, an acinar tumor of the pancreas or a pancreatic tumor with mixed histologies.
At least 1 measurable tumor lesion, as defined by mWHO criteria, that is not located in a previously irradiated area
T3 tumor defined by invasion of key structures (only T3 defined by size > 7 cm allowed)
Well-differentiated liposarcoma or atypical lipomatous tumor
Gastrointestinal stromal tumor (GIST)
Solitary fibrous tumor
PEComa (perivascular epithelial cell tumor)
Myoepithelioma / mixed tumor
Test results showing genetic change in tumor gene for CREBBP and/or EP300
At least one tumor that can be measured
Uncontrolled tumor in the brain
Patient has a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative will be included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
Patient has a confirmed diagnosis of a select solid tumor (except ALK+ NSCLC) or hematological malignancy and is in need of treatment because of radiologic progression or relapse.
Patient's esophageal tumor length exceeds that which can be treated with a single stent (maximum lesion length 9.5cm)
Metastatic disease that involve major airways or blood vessels, or centrally located mediastinal tumor masses (< 30 millimeter from the carina) of large volume
NET tumor other than PNET or GI-NET
Macroscopic complete resection of the primary tumor must be planned
Patients must have tumor accessible by interventional radiology or surgical intervention and suitable for biopsy with 5-6 passes of a 16 or 18 gauge needle for core biopsy (defined as at least 1 cm^3 tumor/50 mg accessible for biopsy), and must agree to undergo up to two surgical resections/biopsies to collect tumor for research purposes; the first of these biopsies will occur at the beginning of the study, prior to genetic analysis and treatment; the second biopsy will be performed at the time of disease progression/end of study should funding be available
Patient agrees to having a blood sample (approximately 10 mL) drawn and analyzed to compare their normal genetic profile to that of their tumor sample
At least 12 weeks from prior radiotherapy to the start of SL-701 unless there is new enhancement outside of the radiation field or unequivocal histopathologic evidence of recurrent tumor.
Contrast-enhancing tumor that is any of the following:
History of cancer (other than GBM) within the past 2 years that has metastatic or local recurrence potential and could negatively impact survival and/or potentially confound tumor response assessments within this study.
Is willing to provide pre-existing diagnostic or resected tumor samples, such as paraffin-embedded sections. Providing a fresh tumor biopsy sample is optional.
Subjects with cutaneous melanoma must provide either a fresh or archived tumor sample for genetic analysis including determination of or confirmation of BRAF and NRAS genetic status based on local laboratory results. To ensure prompt delivery of tumor samples, tissue shipment tracking information must be provided before administration of study treatment can be initiated.
Must provide either a fresh or archived tumor sample for genetic analysis.
Accessible tumor for biopsy and willingness to provide pre-dose tumor biopsies on Days 1 and Day 15.
An adequate tumor specimen obtained by either excisional biopsy, incisional biopsy or core needle biopsy must be sent to the central pathology lab for evaluation. The material must measure at least 0.8 × 0.1 cm in size or contain at least 50 tumor cells.
An inadequate tumor specimen as defined by the central pathologist.
Mixed tumor histology
By tumor biopsy if conducted within 4 weeks of randomization.
An interval of at least 12 weeks after last dose of radiation and temozolomide is required, unless cancer progression is proven by diagnostic tumor biopsy. If temozolomide is being used in a maintenance phase, there must be a 28-day washout period prior to Randomization.
Tumor must be glucocorticoid receptor positive TNBC (?10% positive cells by IHC of tumor biopsy)
Unknown primary tumor.
Does the patient have either (1) a single, enhancing tumor recurrence/progression that is ? 8 cm in greatest dimension, or (2) multiple enhancing tumor recurrences/progressions within the same surgical field where the sum of their greatest dimensions is ? 8 cm?
Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate for ? 80% resection?
Patients may choose to undergo an optional tumor biopsy including collection of research blood samples pretreatment and at weeks 3 and 15
Infra-tentorial tumor
Subject has available and has provided consent to release to the sponsor (or designee) a tumor block with confirmed tumor content (or approximately 20 unstained charged slides [a minimum of 7 slides is mandatory]) and the corresponding pathology report
Biopsy proven HER2 negative metastatic breast cancer (dose escalation portion and MTD expansion portion) or advanced solid tumor (dose escalation portion).
Subjects must provide tumor biopsies before treatment
Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
Have metastatic RCC with primary tumor in place
Histologic proof of presence of residual tumor in liver explants and /or positive resection margins
The subject has tumor in contact with, invading, or encasing major blood vessels
Patients with a known history of NF1 (Neurofibromatosis Type 1) and either \r\n* A history of a tumor of the central nervous system (astrocytoma or optic glioma), or \r\n* A malignant peripheral nerve sheath tumor with a complete remission of < 1 year are not eligible
Arm 2 only: At least 1 tumor that is amenable to biopsy, as determined by the investigator, and participant must be willing to undergo a biopsy prior to and at least once following anti-macrophage migration inhibitory factor (anti-MIF) antibody treatment
Patients with a malignancy that is currently not amenable to surgical intervention, due to either medical contraindications or non-resectability of the tumor.
AST or ALT > 3× the ULN for the institution (> 5× ULN if due to hepatic involvement by tumor)
Anti-tumor therapy
Participants who developed disease progression/ requiring other anti-tumor therapy while in the parent protocol
Available tumor site amenable to core needle biopsy as determined by the treating investigator; any questions regarding suitability of site for biopsy will be adjudicated by the principal investigator
Tumor (primary or metastatic lesion) defined as MET-positive by IHC
HER2-positive tumor (primary tumor or metastasis)
Availability of histological material (primary tumor or metastases) for review of the diagnosis and demonstration of PAX8-PPARgamma fusion gene
Biopsy accessible tumor (may use archived tumor samples under certain circumstances)
If the maximum number of non-biopsy subjects has accrued to the study, willingness to undergo 2 tumor biopsies. NOTE: Tumor biopsies may be required, depending on the number of subjects who have agreed to undergo correlative studies.
For dose escalation, tumor type that has high biomarker prevalence without molecular confirmation of biomarker status, or any tumor type with molecular confirmation of biomarker status; For MTD cohort expansion, only dedifferentiated liposarcoma will be included.
Calculated required PV-10 dose ? 15 mL (based on total tumor burden)
Maximum tumor length of 7 cm at time of brachytherapy treatment start
History of symptomatic metastatic brain or meningeal tumors unless the subject is >3 months from the end of definitive therapy before the first dose of study drug and has clinically or radiologically no evidence of tumor growth.
Solid tumor cohort (B1) specific criteria
Subjects with NF-1 associated optic pathway tumors are excluded if they are actively receiving therapy for the optic pathway tumor or do not meet criteria for PN or malignant solid tumor.
Subjects with NF-1 actively receiving therapy for the optic pathway tumor.
Tumor deemed unresectable or metastatic
Advanced or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathological report
AR expression >= 5% by immunohistochemistry (IHC); in cases where multiple blocks are available staining will be performed on unstained slides from 3 separate blocks; if >= 5% AR tumor staining is seen on >= 1 slide the tumor will be considered to be AR+
Direct tumor extension into aorta or pulmonary artery
The subject has tumor invading or encasing any major blood vessels
The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
The subject has tumor invading major blood vessels
The subject has any evidence of an endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Histologically proven ependymoma or anaplastic ependymoma; there must be pathologic or imaging confirmation of tumor progression or regrowth; the patients histologic diagnosis must be confirmed on central pathology review prior to registration step 2
Patients with nodal disease limited to micrometastases (pN1Mi, > 0.2 mm and =< 2 mm) or isolated tumor cells (pN0i+ < 0.2 mm)
Patients with ovarian tumors of non-epithelial origin (eg, germ cell tumor) or any low grade tumors.
Uncontrolled tumor-related pain
A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
Neurosurgical patient population in the City of Hope brain and spinal tumor neurosurgical programs that have been diagnosed with a brain tumor
Patients with any type of brain tumor will be eligible for participation
i2DOS will be attempted for all quantities, consenting, and brain tumor patients; we anticipate approximately 5 initial patients will need to be imaged before signal to noise parameters are optimized; then 1 patient from the most common operative tumor types (e.g. low grade glioma, glioblastoma multiforme, astrocytoma, invasive meningioma, metastatic breast carcinoma, etc.) will be imaged to ascertain gross intrinsic optical spectroscopically differences that may distinguish these tumors from each other and normal white matter, gray matter, and blood vessels
There are no exclusion criteria except for individuals without a brain tumor and the location of the craniotomy; if the exposed area of brain is not compatible with peripheral stimuli or volitional activity the subject cannot be enrolled
HER2-positive as assessed by local laboratory on primary or metastatic tumor
Participants must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) prior to fiducials placement and subsequent SBRT; because fiducials will be placed exclusively by ENB, which can also be used for pathological diagnosis of malignancy, there will be two categories of eligibility:\r\n* Participants already carry a histological or cytological diagnosis of NSCLC and will undergo an ENB procedure solely for the placement of fiducial tumor markers; participants in this category need not be newly diagnosed; a participant who was previously histologically or cytologically diagnosed with NSCLC and now presents with a new tumor confirmed by imaging may be treated on this protocol without an additional biopsy; in this case, the prior pathological diagnosis will be used to establish a NCLC diagnosis for this protocol\r\n* Participants present with an indeterminate lung tumor and undergo ENB for both NSCLC diagnosis and fiducials placement; in this setting, the subject will sign informed consent prior to the ENB procedure and be enrolled only after intraoperative histological or cytological confirmation of NSCLC and placement of fiducial markers
The participant’s target lesion must be limited to a single biopsy-confirmed tumor; presence of other pulmonary nodules, which may represent synchronous early lung cancer, is allowed as long as no additional therapy is anticipated within 3 months following protocol therapy
For certain subjects, willing and able to provide pre- and post-treatment fresh tumor biopsies
Patients with stage IV renal cancer\r\n* Patients in the initial cohort receiving CT-011 alone are not required to have tumor resection as a part of protocol participation\r\n* Patients in the second cohort are eligible if they are undergo therapeutic debulking nephrectomy for independent clinical indications OR patients with other sites of accessible disease as defined by peripheral lung nodules approachable by thoracoscopy, malignant effusions, or cutaneous, subcutaneous or superficial lymph node involvement; patients should have an independent diagnostic or therapeutic indication for this purpose; tumor tissue should be at least 1.0 cm in longest dimension to provide an adequate source of tumor cells for vaccine generation
Biopsy proven ER/PR positive tumor
Tumor that lacks both estrogen and progesterone receptors
Patients with solid tumor other than CRC.
Pathologic proven diagnosis of solid tumor malignancy
Pathology specimens (example [e.g.], tumor blocks or unstained slides) for potential centralized pathology review and biomarker studies
Collection of the specimen: Pathology specimens (example (e.g.), tumor blocks or unstained slides) for potential centralized pathology review and biomarker studies is not applicable
Biopsy accessible tumor (may be waived under certain circumstances)
For NSCLC, an ALK translocation must be detected by FISH in ? 15% of tumor cells.
Participants who are clearly disease-free after transurethral resection of bladder tumor (TURBT)
Measurable disease demonstrating intratumoral arterial enhancement by contrast enhanced computerized tomography (CT), with use of multislice scanners, or contrast enhanced dynamic magnetic resonance imaging (MRI), with at least 1 tumor lesion that meets the following criteria: located in the liver; can be accurately measured in at least 1 dimension; well delineated area of viable, hypervascular (contrast enhancement in the arterial phase) tumor that is >2 centimeter (cm) in the axial plane; suitable for repeat measurement; OR not previously treated with locoregional or systemic treatment unless the lesion shows a well-delineated area of viable (contrast enhancement in the arterial phase) tumor that is >2 cm in the axial plane. (If the lesion is poorly demarcated or exhibits atypical enhancement as a result of the previous intervention, then it cannot be selected as a target lesion)
Subjects must have a pathologically documented, definitively diagnosed, advanced solid tumor
Presence of at least one measureable tumor lesion is required
for intratumoral cohorts, injection of tumor would require violation of ventricular system
Have at least one BCC tumor (greater than 4mm in diameter) at any skin location, which needs to be biopsied and surgically removed
BRAF mutation positive melanoma or colorectal cancer; other BRAF mutation positive tumor types may be considered.
Tumor size =< 5 cm in greatest dimension \r\n- For NSCLC lesions, staging studies must identify the lesion as T1 N0 M0, or T2 (=< 5 cm) N0 M0, or T3 (=< 5 cm) N0 M0
Tumor size > 5 cm
Histological or cytological documentation of non-hematologic, malignant solid tumor, excluding primary brain or spinal tumors, or history of central nervous system metastases
Patients must have adequate tumor bulk accessible to biopsy in order to generate the tumor lysate (at least 2 cm diameter); procedures employed to acquire biopsies for tumor lysates will be limited to percutaneous biopsies or open biopsies of readily accessible lesions; patients should not undergo biopsies, which will later compromise the ability to render function preserving local therapy (e.g. limb salvage therapy); to prevent this, all bone biopsies should be performed in consultation with the orthopedic consultant on the case; for patients with bone marrow involvement, bone marrow aspirates may be used as a source of tumor for tumor lysates; patients are not eligible if, in the opinion of the principal and associate investigators, tumor biopsy would entail extensive surgery such as thoracotomy or laparotomy, or if the tumor site places the patient a substantial risk from the biopsy procedure; National Cancer Institute (NCI) laboratory of pathology will review all tumor specimens for diagnosis
Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
Patients must have a histologically confirmed solid tumor that is considered incurable and is not amenable to conventional surgical, radiation therapy or chemotherapy treatment programs
large tumor mass (bulky disease)
Tumor thickness must be clinically indicated for hyperthermia therapy, as measured by clinical exam or imaging studies (CT or MRI). The target local tumor lesion(s) must be able to be covered within two hyperthermia fields of treatment.
Patients must have unequivocal evidence for tumor recurrence or progression by histology as determined by review of pathology by an attending neuro-pathologist at UCSF
Patients must have evidence for tumor recurrence or progression by MRI as determined by radiographic review of images by an attending neuro-oncologist or neuro-radiologist at UCSF
The participant must have a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, measurable by elevated tumor markers (eg, 24-hour urine 5-HIAA, chromogranin A, adrenocorticotropin hormone (ACTH), gastrin, or other tumor specific biochemical markers), or both
Disruption of the lung pleura by tumor.
Evidence of ascites, cirrhosis, portal hypertension, main portal or venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.
Pathologically confirmed giant cell tumor of bone within 1 year before study enrollment
Known or suspected current diagnosis of brown cell tumor of bone or Paget's disease
Paraffin-embedded tumor tissue from primary tumor or metastasis for determination of epidermal growth factor receptor expression and biomarker testing
Tumor must be accessible for injection and must not be located in the brainstem, midbrain, contained within the ventricular system, or located in an infratentorial location.
May not receive other investigational anti-tumor agents within 30 days prior to study entry or during active participation in the study (defined as from AdV-tk injection until tumor progression).
Other tumor histologies\r\n * Patients with tumor histologies not listed above will be considered on a case by case basis; to be eligible for this study, such patients must have an expected probability of survival =< 20% with other therapeutic modalities and must minimal disease criteria as defined in eligibility criteria
Kidney tumor has been removed
Greater than 50% tumor burden in the liver by imaging
Uncontrolled tumor-related pain
Presence of a muscle invasive bladder tumor(s) (T2), specific for transitional cell carcinoma on pre-operative histology (i.e. biopsy or transurethral resection of bladder tumor [TURBT]).
Presence of a single bladder tumor lesion
Primary tumor deemed unresectable by hepatobiliary surgeon
Patient is after surgical resection of the tumor where tumor was removed completely with surgical specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical specimen
Prior embolization, chemoembolization, or radiofrequency ablation permitted if >= 4 weeks from registration and evidence of new tumor growth is present
Tumor expression of NY-ESO-1 by immunohistochemistry (IHC) and/or real-time polymerase chain reaction (RTPCR)
All patients must consent to provide archival tumor samples; non-availability of evaluable tumor samples does not exclude patient from the study
Phase II: The initial 20 patients must have evaluable baseline tumor samples; evaluable samples are defined as those obtained by core biopsy or surgical resection and amendable to histological analysis; samples obtained by fine needle aspiration biopsy are not considered evaluable; patients who do not have evaluable archival tumor samples must consent to a tumor core biopsy prior to starting study treatment and, patients who consent to the baseline tumor biopsy will be eligible to receive study treatment irrespective of whether the samples obtained are evaluable
Tumors with a depth of not greater than 3.0 cm from a laparoscopically accessible surface-meaning no part of the tumor should be deeper than 3.0 cm from the surface
Subjects having had prior ablation therapy on the same tumor
Consent to allowing his/her archival tumor tissues to be requested and analyzed; however, the non-availability or inadequate amount samples for analysis will not exclude the patient
Maximum tumor dimension =< 5 cm
Tumor verified by a thoracic surgeon to be in a location that will permit a sublobar resection
Tumor thickness is 4 mm or less (in the judgment of the physician)
Tumor accessible for unrestricted illumination for photodynamic therapy (PDT) (accessibility as determined by the physician)
Histologic diagnosis of a well- to moderately differentiated PNET (low-intermediate grade); NOTE: pathology report should state one of the following: low-grade, intermediate grade, moderately- or well-differentiated NET, pancreatic NET (or neuroendocrine carcinoma of the pancreas); patients who have tumors with a Ki67 of 20 % - 30 % are eligible if the pathologist determines the tumor has the appearance of a well- to moderately differentiated neuroendocrine tumor
The contrast-enhancing intraparenchymal brain tumor must be well circumscribed and must have a maximum diameter of =< 4.0 cm in any direction on the enhanced scan; if multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter
Has histological diagnosis of a primary solid tumor malignancy that meets study criteria
Patients with stage IB1 with tumor size (maximum visible or palpable) > 2 cm
Patients scheduled for amputations as local control of their tumor
Radiographic evidence of cavitary or necrotic tumor and local invasion of major blood vessels
Adults with a primary diagnosis of any advanced solid tumor cancer within the last 3 years
Targeted bone/tumor interface (most painful lesion) size up to 55 cm2 in surface area
Targeted tumor is at an impending fracture site (>7 on fracture risk score, see Section 7.4). OR
Patients with surgical stabilization of tumor site with metallic hardware
Targeted (treated) tumor is in the skull
Target (treated) tumor is less then 1cm from nerve bundles, bowels or bladder.
Targeted (most painful) tumor Not accessible to ExAblate
The targeted tumor is less than 2 points more painful compared to other painful lesions on the site specific NRS.
Radiologic suspicion of lung involvement (primary or metastatic), lymphangitic carcinomatosis, or airway involvement secondary to tumor infiltration.
Pathologically proven solid tumor malignancy (except for small cell lung cancer [SCLC], germ cell tumor)
Solid tumor survivors with no evidence of disease
Solid tumor cancer diagnosis
Enrollment within 6 weeks of tumor board review
able to provide adequate tumor tissue from at least 1 accessible tumor site
Subject's tumor (either the most recent archival specimen or a fresh biopsy) shows positive NY-ESO-1 expression defined as ?30% of cells that are 2+ or 3+ by immunohistochemistry. All samples must have been pathologically reviewed by an Adaptimmune designated central laboratory.
Biopsy-proven tumor invasion of the tracheobronchial tree or presence of tracheoesophageal fistula; recurrent laryngeal or phrenic nerve paralysis
Uncontrolled tumor in the brain
Infra-tentorial tumor.
Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening
All subjects must have a fresh tumor biopsy
Histological or cytological documentation of an invasive malignancy that was diagnosed as locally advanced/metastatic or relapsed/refractory and is of one of the following tumor types:: bladder; cervical; colorectal (includes appendix); esophagus, squamous cell; head and neck; melanoma; malignant pleural mesothelioma (MPM); non-small-cell lung cancer (NSCLC), prostate; Microsatellite Instability-High/deficient mismatch repair (MSI-H/dMMR) tumor (Part 1B and Part 2B) and Human Papilloma Virus (HPV)-positive or Epstein-Barr (EBV)-positive tumor (Part 1B and Part 2B.
Documented HPV/ EBV-positive tumor as determined by a local laboratory for Part 1B and Part 2B pembrolizumab combination viral-positive expansion cohorts only
Any tumor grade
Pathologically-confirmed solid tumor or hematologic malignancy with symptomatic bone metastases
Any patient with a past medical history for a chronic disease (such as sickle cell disease), cancer (solid tumor, lymphoma, brain tumor) and have a current diagnosis which includes pain for which they are being treated, or currently undergoing bone marrow transplant – currently admitted to the hospital
Biopsy-proven neuroendocrine tumor with tumor burden dominant in the liver
Show no current evidence of disease (NED) for solid-tumor cancers.
>= 10 core prostate biopsy completed prior to randomization with at least 2 mm of tumor and Gleason sum =< 6 with no pattern 4 or Gleason 3+4 in < 34% of all cores; AND residual tumor tissue from such biopsy is obtainable and donated for the research
NON-RANDOMIZED OBSERVATIONAL COMPONENT ELIGIBILITY:\r\nBiopsy prior to study enrollment that is obtainable AND has sufficient residual tumor tissue from such biopsy is obtainable and donated for the research
All patients must have histologic proof of solid tumor malignancy and radiographic evidence of spine metastasis
Treatment for solid tumor cancers
Posterior fossa tumor/approach for tumor resection requiring the prone position
Extremity or central axis (including craniofacial) primary tumor; localized or metastatic
Incurable solid tumor malignancy
Patients must have limited disease SCLC after clinical staging evaluation: clinical tumor, lymph nodes, metastasis (TNM) stages I-IIIB (i.e., confined to one hemithorax, but excluding T4 tumor based on malignant pleural effusion and N3 disease based on contralateral hilar or contralateral supraclavicular involvement) according to American Joint Committee on Cancer (AJCC) 1997 staging manual to be consistent with Radiation Therapy Oncology Group (RTOG) 0212
Subjects with histological diagnosis of incurable cancer (solid tumor)
Diagnosis of a primary brain tumor treated with at least one of the following:\r\n* Neurosurgical resection of the brain tumor\r\n* Cranial irradiation\r\n* Any chemotherapy to treat the brain tumor
Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test
Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands
Newly (within 1 month) diagnosed with a primary malignant brain tumor (PMBT) (tumor verified via pathology report to be a glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, medulloblastoma, or anaplastic ependymoma)
Patients with stable metastatic disease which is defined as (metastatic tumor demonstrates no increase in volume, tumor size or diameter and no evidence of new lesions, have been identified during last assessment by medical oncologist/radiologist or surgeons)
Individuals with progressive metastatic disease in which the tumor has increased in size, volume and diameter or evidence of new lesions, as noted by medical oncologists, radiologists and surgeons
Subjects must have or have had at initial diagnosis, histologic proof of their malignancy; additionally they must have radiographic, nuclear image, or biopsy proof that they have had a recurrence of their disease within four weeks prior to study entry; subjects must have failed or relapsed from standard first-line chemotherapy for their tumor; young children with primary embryonal brain tumor treated according to Head Start protocol are eligible as well; subjects with bone marrow involvement are NOT eligible for study
A personal history of cancer, tumor, or a related illness
Diagnosis of a metastatic or incurable solid tumor
Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC): defined as localized PDAC with 1 or more of the following features: a) an interface between the primary tumor and superior mesenteric vein (SMV)-portal vein (PV) measuring 180 degrees or greater of the circumference of the vein wall, and/or b) short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction and/or c) short-segment interface of any degree between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction and/or d) an interface between the tumor and SMA or celiac trunk measuring less than 180 degrees of the circumference of the artery wall
In Arm 1, subjects must have residual visible tumor following TURBT. In Arm 2, subjects must be fully resected (i.e., no visible tumor or as little tumor as possible) after restaging TURBT 2-6 weeks prior to Study Day 0.
History of MPNST (malignant peripheral nerve sheath tumor) or any malignancy other than asymptomatic and stable optic nerve glioma
Availability at the site of tumor specimens in paraffin blocks (preferred) or 16 unstained slides, with an associated pathology report, prior to study entry
Absence of HER2 expression documented as ISH-negative on previously collected and assessed tumor tissue upon initial diagnosis of disease
Uncontrolled tumor-related pain
Tumor with known or expected RAS/RAF/MEK/ERK pathway involvement. Diagnosis must be one of the following tumor types: Central nervous system gliomas, including high- and low-grade gliomas, and diffuse intrinsic pontine glioma (DIPG) Embryonal rhabdomyosarcoma and other non-rhabdomyosarcoma soft tissue sarcomas Neuroblastoma Melanoma Malignant peripheral nerve sheath tumor Rhabdoid tumors, including atypical teratoid/rhabdoid tumor (ATRT) NF1-associated tumor (including plexiform neurofibroma), schwannoma, or RASopathy-associated tumor that in the judgment of the investigator is life threatening, results in severe symptoms (including severe pain), or is in close proximity to vital structures
Measurable disease as defined by mINRC, RANO, RECIST v1.1, or evaluable by nuclear medicine techniques, immunocytochemistry, tumor markers, or other reliable measures
Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening/baseline, and during therapy on the study.
Folate receptor alpha positive tumor expression as defined in the protocol
Willing to undergo tumor biopsy
Disease-related criteria for Part 1 and Part 2: 1) Histologically or cytologically documented non-small cell lung cancer (NSCLC) - adenocarcinoma; 2) Stage III b or IV disease; 3) Tested for presence of echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement; 4) Received at least 2 prior lines of Food and Drug Administration (FDA)-approved systemic therapy, of which one therapy has to be a platinum-containing regimen OR failed or completed a first-line platinum-containing regimen and refused a second-line regimen despite being informed about the different therapeutic options and their specific clinical benefit by the investigator; the content of this informed consent discussion including the therapeutic options reviewed by the investigator needs to be documented and the subject needs to sign a specific consent form; Disease-related criteria for Cohort 2B only: 1) Mesothelin protein overexpression, defined by immunohistochemistry (IHC) as detection of the protein by greater than or equal (>=) 50 percent (%) of tumor cells on archived tumor material; 2) Primary tumor or metastatic lesion(s) amenable to tumor core biopsies
Participants with non-evaluable or non-measurable cancer are eligible if they have a confirmed increase in tumor antigens >=2 x upper limit of normal (ULN).
Subjects must consent to allow for the acquisition of tumor sample prior to starting treatment on study (in most cases patients will require a tumor biopsy); this biopsy site may be the only site of measurable disease if the site is > 2 cm; the biopsy site must, in the opinion of the investigator, be likely to yield acceptable tumor sample for core biopsies; it is also acceptable if tumor sample is obtained by excision biopsy or during surgery (i.e. if procedure was previously planned), provided the tumor sample can be processed; in the case that a patient had a tumor sample acquired prior to consenting to the study and this tumor sample is acceptable for processing (i.e. frozen sample stored) and the tumor sample was acquired within 60 days of starting treatment, this is acceptable and a new biopsy will not be required
The greatest dimension of the tumor is less than 4 cm before surgery
Patients with proven multicentric carcinoma (tumors in different quadrants of the breast or tumor separated by at least 4 cm)
Tumor bed is less than 5 mm from the skin surface
Patients with skin involvement, regardless of tumor size
Histological confirmation of tumor of the oral cavity, oropharynx, supraglottic larynx, or nasopharynx
Incomplete tumor resection (R2 resection, grossly positive resection margin)
Known malignant primary brain tumor
Clinical or radiologic history of lung/pleural involvement (primary or metastatic), lymphangitic carcinomatosis or airway involvement secondary to tumor infiltration
Patients with =< 10 cc largest tumor volume, and =< 15 cc total tumor volume
The patient has a clinical negative node status at the time of study entry (i.e. T0-4, M0, tumor staging criteria)
Tumor resection candidates
Tumor extends beyond kidney into major veins, perinephric tissues, or adrenal gland
Has tumor(s) of the lips, sinuses, salivary glands, nasopharynx, glottic larynx, subglottic larynx or unknown primary tumor
?1 cm of tumor-free lung parenchyma between target tumor and pleura or fissure.
Tumor with pleural contact.
Patients undergo recanalization procedure of tumor during bronchoscopy
Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, salivary glands or unknown primary tumor
Macroscopic resection of the tumor via TORS must be planned with curative intent
Has undergone prior ablation treatment of the index tumor
Anticipated treatment of the index tumor that would require iceball formation within 1.0 cm of the spinal cord, brain, other critical nerve structure, large abdominal vessel such as the aorta or inferior vena cava, bowel, or bladder
Surgery at the tumor site or surgery involving the cryoablation-treated tumor (index tumor)
Index tumor involves the skull (treatment of other painful tumors in subjects with skull tumors is not excluded)
ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have a formalin fixed paraffin embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto pediatric MATCH for children with diffuse intrinsic pontine gliomas (DIPG, brainstem gliomas)
Newly diagnosed with a primary invasive colorectal adenocarcinoma (all stages) and have a resection at any hospital in Ohio between 1/1/2013 and 12/31/2015\r\n* For individuals who have neoadjuvant treatment and show a complete response at resection, the tumor screening will be attempted on their original biopsy (even if it occurred in 2012) as long as their resection occurred between 1/1/2013 and 12/31/2015\r\n* Many individuals with stage IV CRC will not have a resection; therefore, the tumor screening will be attempted on their original biopsy as long as their primary diagnosis occurred between 1/1/2013 and 12/31/2015; if only metastatic CRC is available on a biopsy, tumor screening will be attempted on the metastatic tissue
Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed:
Tumor imaging studies including
Tumor in a location where enlargement could cause airway obstruction
Malignancy or mass that is non-gynecologic in origin (mass/tumor of origin other than reproductive organ such as rectal, abdominal, breast)
The clinical or radiologic primary tumor size is at least 1.5 cm diameter
Primary tumor sample was collected before NACT began and was evaluated for genomic testing (integral biomarker)
Patients with hematomas or biopsy site changes that limit response assessment of the primary tumor by diagnostic imaging
Patients must be eligible for surgical resection according to the following criteria:\r\n* 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\r\n* 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
Provision of written informed consent for tumor resection, stereotactic surgery, tumor biopsy, samples collection and treatment with investigational products prior to undergoing any study procedures
Determined unresectable by a pancreatic cancer surgeon or a multi-disciplinary or gastrointestinal oncology Tumor Board
Patients with tumors of two different subtypes will be eligible provided that the triple negative tumor otherwise meets eligibility requirements, and the non-triple negative tumor is < 1.0 cm in size
In the event that a tumor is in contact with the capsule, the length of the contact should be ? 5 mm, on axial images.
Tumor distance, including tumor free margins, should not be more than 40mm from the rectal wall.
Subject's tumor(s) must be < 3.0 cm in greatest diameter by pre-operative assessment
Subject's tumor(s) must meet AJCC Tumor Classification: Tis, T1 or T2 (< 3 cm), N0, M0
Eligible patients in the dose escalation phases of the trial must agree to biopsies of normal skin, unless they undergo optional tumor biopsies; the mandatory biopsy requirement can be waived at the discretion of principal investigator in the event of any medical contraindication (e.g. lidocaine allergy); patients enrolled to the expanded cohorts must agree to tumor sampling; patients on anticoagulation must be able to hold warfarin or low molecular weight heparin for a sufficient amount of time to make skin and tumor biopsies safe to perform; PT/INR and PTT should be =< 1.5 times the institutional upper limit of normal prior to performance of skin or tumor biopsies, with values re-checked after the eligibility screen as medically indicated
Patients must have proven positive tumor sample for NY-ESO-1 as follows:
Patients with tumor-induced seizures must be well controlled on a stable anti-epileptic treatment
Not eligible for Stereotactic Radiosurgery (SRS) treatment of brain tumor.
Other completely resected stage 1 solid tumor with low risk for recurrence
HER2/neu-expressing tumor (IHC 1-3+ and or positive FISH >1.2)
Patients without breast biopsy marker documented by imaging at tumor bed site prior to initiation of neoadjuvant therapy
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
Histologic diagnosis of solid malignancy (excluding brain tumors and lymphoma) that meets at least one of the following criteria:\r\n* Refractory, defined as tumor progression after initiation of standard first line therapy without having achieved a prior partial or complete remission OR biopsy proven residual disease at the completion of planned standard initial front-line therapy\r\n* Recurrent, defined as tumor progression after achieving a prior partial or complete remission\r\n* Newly diagnosed high risk disease, defined as having an expected event free survival of < 50% at 2 years\r\n* Lacks definitive diagnosis or classical genomic findings after histologic review and standard molecular testing (rare tumor group)\r\n** Examples include (eligibility not limited to these examples): \r\n*** Histology typically associated with a fusion in which fusion is not detected \r\n*** Ewing-like sarcoma \r\n*** Undifferentiated sarcoma\r\n*** Inflammatory myofibroblastic tumor without ALK fusion\r\n*** Infantile fibrosarcoma without NTRK fusion
Sufficient tumor specimen thought to be available to meet the minimum requirements for profiling from diagnosis or progression/recurrence; OR
Willingness to undergo tumor biopsy prior to initiation of treatment
Inability to obtain a biopsy of the tumor as deemed by the study interventional radiologist
Subjects may be enrolled at one of three time points in the clinical course of disease:\r\n* Study 1 (New Diagnosis): \r\n** Pediatric patients with newly diagnosed primary central nervous system tumors undergoing surgical resection/biopsy within 21 days or who, within the prior 21 days, have undergone resection/biopsy with substantial residual (greater than half as assessed by the surgeon) tumor\r\n* Study 2 (Possible Tumor Recurrence): \r\n** Pediatric patients with a history of treated primary central nervous system tumor, in whom standard imaging has raised concern for tumor recurrence; tumor tissue for histological analysis must be available from a biopsy/resection planned within the next 21 days or from a prior resection/biopsy if no current biopsy material is available\r\n* Study 3 (Response to Therapy): \r\n** Pediatric patients with a primary central nervous system tumor who will be starting a new regimen (standard or experimental) of chemotherapy within 21 days, have not received radiation therapy during the past six months, and who will not be receiving radiation therapy during the first two cycles of chemotherapy
Tumor site amenable to MRI guided biopsy as determined by the radiologist
Pre-operative spirometry that suggests the patient cannot undergo resection of the primary tumor by segmentectomy, lobectomy, bilobectomy, or pneumonectomy
Children with a diagnosis of a brain tumor and who do not require sedation for MR imaging
Sufficient archived tumor material available (equivalent to 2 core biopsies or greater); if insufficient archived tumor material available new tumor biopsy is mandatory
For patients who undergo optional metastatic tumor biopsy following completion of gallium citrate PET:\r\n* Presence of one or more metastases by standard radiographic scans including cross-sectional imaging of the chest/abdomen/pelvis and whole body bone scan that is safely accessible to tumor biopsy in the judgment of treating clinician and/or interventional radiology\r\n* No history of radiation therapy to the target metastatic lesion selected for tumor biopsy\r\n* No contra-indication to biopsy including uncontrolled bleeding diathesis\r\n* Platelets > 75,000/ul\r\n* Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time (PTT) =< 1.5 times the institutional upper limit of normal (ULN) within 14 days prior to biopsy
Referral from an internist, oncologist, or surgeon for liver tumor ablation consultation
Liver tumor ablation judged to be appropriate based on clinical assessment in the Brigham and Women’s Hospital (BWH) Tumor Ablation Clinic by the tumor ablation interventional radiologist, per standard clinical practice
The tumor must be >= 1 cm and =< 6 cm
Primary tumor size > 6 cm
Resection: tumor must be judged suitable for resection on the basis of imaging studies
(Part 2, intracranial tumor patients ONLY): Radiographical or pathological evidence of an intracranial tumor
(Part 2, intracranial tumor patients ONLY): Other chemotherapy (besides what is being used to treat the intracranial tumor)
Subjects not deemed to be appropriate candidates for optimal resection of tumor based on location, involvement of eloquent brain, satellite lesions, or other factors not specifically listed here
Active metastatic cancer in addition to malignant primary brain tumor
Patient is a candidate for cerebral tumor resection with lesion suspected to be or previously biopsy proven to be a primary brain tumor.
Tumor(s) must be located near air cavities
Results of CXCR4 immunohistochemistry or slides from biopsy of primary tumor or metastatic lesions available for study analysis
Participation in the Iowa Neuroendocrine Tumor Registry
Inadequate tumor sites or volume to allow for biopsy per standard of care
Two adult patient groups will be eligible for inclusion in this study: \r\n* Group A: Patients where there is compelling evidence, based on the MRI and/or CT imaging, that a high-grade primary brain tumor is present; pathologic confirmation will occur with biopsy or surgery; patients whose tumor is felt to be inoperable and a biopsy is performed but no surgery; patients with a newly diagnosed primary malignant brain tumor (World Health Organization [WHO] grade III or IV) who will be receiving chemoradiation and who either did not undergo surgical resection or underwent incomplete resection with residual tumor >= 1.0 cm in greatest diameter by contrast MRI postoperatively\r\n* Group B: Patients with pathologically proven malignant brain tumor (WHO grade III or IV glial-based tumors) who have undergone chemoradiation and have MRI-documented possible recurrence/progression versus treatment effect (pseudoprogression) within 6 months from the time of completion of chemoradiation
Subjects with a presumed diagnosis of brain tumor (based on imaging) or a confirmed brain tumor (based on pathology) before or after any oncologic treatment (surgery/chemotherapy/radiation)
Patient is referred for 90Y SIRT radioembolization of liver tumor(s)
Patients with measurable colorectal liver metastases on prior imaging, with at least one tumor greater than 2.0 cm in axial maximal diameter
Biopsy or resection of the primary tumor within 14 days the first injection of [18F]F-AraG
Previous diagnosis of a brain tumor; patients who are either undergoing active treatment for a brain tumor or who have completed treatment will be eligible for study enrollment (Cohort 2)
Presence of at least one target lesion amenable to percutaneous tumor biopsy in the judgment of interventional radiology
Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy
For patients undergoing optional tumor biopsy:\r\n* No history of bleeding diathesis\r\n* Patients on anti-coagulation they must be able to safely stop treatment for purposes of tumor biopsy
Patients with an extracoelomic solid tumor requiring SLN biopsy
No known endobronchial tumor
Tumor located anywhere in parenchymal tissue >1 cm from pleura and accessible bronchoscopically through a POE.
Inoperable tumor/nodule
Metastatic or primary malignant tumor involving spinal column, with or without extension into the epidural space
Intradural extension of the tumor
Patients undergoing a tumor resection at the University of Texas M. D. Anderson Cancer Center for a newly diagnosed primary or metastatic brain tumor located in or adjacent to motor brain areas
Patients presenting with a CNS tumor presumed to be resectable and are at risk for local recurrence on pre-operative assessment
Histopathologic or imaging and clinical features of tumor(s) diagnostic for hepatocellular carcinoma with at least one tumor >= 1.5 cm; imaging features diagnostic for hepatocellular carcinoma will be defined as Liver Imaging Reporting and Data System (LI-RADS) 4 or greater
Tumor amenable to transcatheter arterial embolization
Kinetic Studies Arm only:\r\n* Participant with a suspected or confirmed cancer diagnosis who is scheduled for surgical resection, biopsy, or chemotherapy treatment\r\n* One or more tumor sites measuring >= 1 cm in the shortest transaxial diameter by CT
Histologically diagnosed or suspected (pediatric only) neuroendocrine tumor or other tumor with probable somatostatin receptors subtype 2
At least part of the tumor must be visible as observed in a diagnostic or planning CT
Subject has a tumor that will undergo upfront resection
Subject has undergone primary tumor resection prior to arrival at St. Jude
Willing to provide existing relapse-confirmatory DLBCL tumor sample
Tumor judged to be suitable for open cranial resection based on preoperative imaging studies
GROUPS 1, 2, AND 3: Must be consented for the Oregon Pancreatic Tumor Registry (OPTR)
Tumor must measure >= 2 cm on CT
New or increased enhancing brain lesion(s) OR nonenhancing brain lesion(s) if receiving anti-angiogenic therapy, which is considered indeterminate for tumor progression versus (vs) radiation injury by the neuroradiologist or clinician
Less than 5 mm distance of the tumor margin from a major vessel (> 7 mm in diameter)\r\n* This will not be considered exclusion when irreversible electroporation (IRE) is used
The patient must have a newly diagnosed primary malignant brain tumors (World Health Organization [WHO] grade III or IV glial-based tumors) and not have had a complete surgical resection and by contrast MRI (obtained for clinical purposes within 28 days prior to FMISO study) have residual tumor >= 1.0 cm in greatest diameter and will be receiving radiotherapy or newly diagnosed brain metastasis (>= 1.0 cm in greatest diameter or dimension) and will be receiving radiotherapy; an anatomic imaging study (clinical MRI of the brain) must be current and have been obtained within 28 days prior to the research PET imaging sessions; in patients with a primary brain tumor the patient may be studied after biopsy or after surgery if an incomplete surgical resection has occurred and >= 1.0 cm of enhancing tumor is present; only patients intended to receive radiation therapy will be eligible
Archived tumor blocks must be provided for all subjects for correlative analysis before or during treatment with pazopanib
Pre-operative radiation to primary tumor site
Subject has been diagnosed with melanoma, rhabdomyosarcoma, or other tumor where tumor resection or biopsy is planned and lymph node mapping is appropriate
Breast cancer from ER+ primary that is seen on other imaging tests; tumor ER expression must have been confirmed by immunohistocytochemistry of primary tumor or recurrent disease
Tumor is accessible for local injection of the sentinel node tracer (for example oral cavity disease)
Pathologically confirmed, locally advanced, malignancy of the rectum; based on multi-disciplinary tumor board discussion, patients are candidates for tri-modality treatment
Minimum tumor dimension >= 1 cm (preferably >= 2 cm)
Pathologically confirmed, locally advanced, malignancy of the esophagus; the cancer may involve the stomach up to 5 cm; based on multi-disciplinary tumor board discussion, patients are candidates for tri-modality treatment
Subjects with at least 1 lesion of tumor of the breast
History of mental retardation unrelated to brain tumor
Biopsy proven neuroendocrine tumor, neuroblastoma, medulloblastoma, or other somatostatin receptor positive tumor
Patients in whom the tumor might not be accessible for peritumoral injection of indocyanine green, e.g. small, central tumors
Either the primary tumor or at least one of the metastatic lesions must be >= 2 cm
Pathologically confirmed breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy
Primary tumor 2.0 cm or greater, and/or clinical evidence of axillary disease (palpable N1 or N2 or biopsy proven)
Known or suspected somatostatin receptor positive tumor such as carcinoid; neuroendocrine tumor; neuroblastoma; pheochromocytoma; supporting evidence may include MRI, CT, biochemical markers, and or pathology report
Subjects with a current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas) are not eligible
Patient must not have received craniospinal radiotherapy or involved field radiotherapy to the local tumor (and/or tumor designated as “measurable” for protocol purposes) =< 24 weeks prior to study entry; focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry
The tumor will be evaluated by both mammography and ultrasound
Human papilloma virus (HPV) negative tumor for patients with oropharyngeal cancers.
c-MET overexpression, ? 50% tumor cells with immunohistochemistry Grade 3+
Archival tumor specimen according to protocol-defined criteria.
MAGE-A3/A6 positive tumor
Subject's tumor has AFP expression of ?2+ in ?40% tumor cells by immunohistochemistry and their non-cancerous liver tissue has ?5% cells stained for AFP by immunohistochemistry.
Histologically proven: neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma/ primitive neuroectodermal tumor, Wilms tumor, desmoplastic small round cell tumor or malignant solid tumors of any other histology that test positive for B7-H3 .
Must have malignant solid tumors that demonstrate B7-H3 expression at 2+ or greater levels on the membranous surface of at least 10% of tumor cells or ? 25% of tumor vasculature by IHC.
The primary tumor must originate in the esophagus; tumors that involve the gastroesophageal (GE) junction must meet Sievert type 1 criteria: “adenocarcinoma of the distal oesophagus which usually arises from an area with specialized intestinal metaplasia of the oesophagus (i.e. Barrett’s oesophagus) and which may infiltrate the esophagogastric junction from above;” for the purposes of this protocol, this will be interpreted as: greater than 50% of the tumor must be above the GE junction or, alternatively, the tumor must involve the GE junction and arise in the setting of biopsy-documented Barrett’s esophagus (specialized intestinal metaplasia)
The first 15 patients with adenocarcinoma will be offered an optional tumor biopsy (typically EGD biopsy) at 8 weeks; starting with adenocarcinoma patient #16, patients must have an accessible tumor and must agree to tumor biopsy at 8 weeks; this will continue to be mandatory until a total of 20 patients have undergone biopsy at 8 weeks
Documentation of IDH1 or IDH2 mutation in any tumor specimen
Recurrent infratentorial tumor
Prior re-irradiation or stereotactic radiosurgery for recurrent disease at the same tumor location intended for HFRT in this study
Maximal tumor diameter > 4 cm
Somatostatin receptor 2 positive tumor as assessed at pre-screening or within 180 d of first drug administration using indium SPECT or gallium PET Patients in Phase 1 must have a histologically or cytologically-confirmed solid tumor in 1 of the following categories:
Histologically confirmed high grade endometrial cancer including grade 3 endometroid, serous, clear cell, malignant mixed Mullerian tumor (MMMT) or any mixed tumor containing one of these cell types
Tumors beyond Milan criteria; this trial does not enroll patients with tumors beyond Milan criteria even from region(s) where transplant listing might still be permissible due to a special regional arrangement; any of the following will exclude the patient from the trial:\r\n* Evidence of extrahepatic tumor\r\n* Unifocal HCC > 5 cm in diameter\r\n* Multifocal HCCs, 4 or more in number\r\n* Multiple (2 or more) HCCs with at least one tumor >= 3 cm
Post treatment subjects will have radiographic abnormalities that may or may not be recurrent tumor
Subjects not deemed to be appropriate candidates for optimal resection of tumor based on location, involvement of eloquent brain, satellite lesions, or other factors not specifically listed here
Have a diagnosis or suspected diagnoses of brain tumor (primary, recurrent, or metastatic) by standard clinical diagnosis such as pathology or imaging
At least 5 mm of tumor on biopsy (can have multiple cores to comprise 5 mm)
PART B: Advanced solid tumor malignancy and the presence of at least one liver metastasis measuring > 1.5 cm in longest diameter in axial dimension on standard anatomic imaging
OR a brain lesion that is concerning for malignancy for which histopathological confirmation is anticipated following enrollment (e.g., biopsy or surgical resection of the tumor is scheduled)
ERUS tumor state of T1
A biopsy-proven histological diagnosis of locally advanced, recurrent or metastatic melanoma of any stage that is surgically resectable and be scheduled for clinically indicated surgical removal of one or more melanoma tumors; additionally, patients must have a resectable tumor nodule >= 1 cm^3 (i.e., either a spherical tumor at least 1.0 cm in diameter or a tumor measuring at least 1 x 1 x 1 cm)
1. Patients with bladder cancer in follow-up for tumor recurrence (Note: Patients must be\n             included only at the first surveillance cystoscopy after a histologically confirmed\n             tumor. The histologically confirmed tumor could either be from a TURB or from a\n             surveillance cystoscopy where a biopsy was taken and a tumor was confirmed by\n             histology)\n\n          2. History of one or more of the following:\n\n               -  Multiple tumors\n\n               -  Recurrent tumors\n\n               -  High grade tumor(s)\n\n        Exclusion Criteria:\n\n          1. Gross haematuria. (Note: Gross haematuria is defined as a heavy bladder bleed\n             resulting in significant amounts of blood in the urine, which may visually limit\n             cystoscopy. Where the haematuria is light, the patient should not be excluded, if in\n             the investigator's opinion, rinsing and/or electro-cautery during cystoscopy will\n             alleviate the haematuria limitations to cystoscopy)\n\n          2. Patients who cannot undergo in-office or operating room cystoscopy (Note: Training\n             patients are eligible even if they cannot undergo operating room cystoscopy)\n\n          3. Patients who have received Bacillus Calmette-Guérin (BCG) immunotherapy or\n             intravesical chemotherapy within the past 6 weeks prior to the procedure\n\n          4. Porphyria\n\n          5. Known allergy to hexaminolevulinate hydrochloride or a similar compound\n\n          6. Pregnancy or breast-feeding (all women of child-bearing potential must document a\n             negative urine pregnancy test before study inclusion and use adequate contraception\n             during the study\n\n          7. Participation in other clinical studies with investigational drugs either concurrently\n             or within the last 30 days\n\n          8. Patient is the investigator or any sub investigator, research assistant, pharmacist,\n             study coordinator, other staff or relative thereof directly involved in the conduct of\n             the protocol\n\n          9. Patients that the investigator believes are unlikely to comply with the protocol, e.g.\n             mental condition rendering the patient unable to understand the nature, scope, and\n             possible consequences of participating in the clinical study, uncooperative attitude\n             or unlikelihood of completing the study
Have a primary tumor measuring >= 1.0 cm
Fresh frozen tumor, and/or paraffin block of biopsy or resected tumor is recommended, but not required to determine expression of somatostatin receptors in tumor by immunohistochemistry and/or quantitative polymerase chain reaction (qPCR)
Known diagnosis of neuroendocrine tumor (NET) or suspected somatostatin receptor (SSTR) positive tumors
There are any other past medical, physiological or demographic concerns; this includes any patients with skin blemishes that are present at the dermis over the tumor, as these are of particular interest for use of this technique
Lymphnode negative and a clinical tumor classification of T2 (?3.5cm)-T4 or with 1-3 positive lymph nodes and a clinical tumor classification of T2-T4 DCIS or LCIS are allowed in addition to invasive cancer at T2 or T3 level.
Tumor sample shipped to Agendia with ? 30% tumor cells or that fails Quality Assurance or Quality Control criteria.
Patients should have at least one tumor deposit that is > 1.0 cm in diameter, and that is amenable to imaging
The primary tumor is not visualized by mammogram or breast ultrasound at the time of diagnosis
Patients with a new or recurrent, presumed or documented, diagnosis of primary or secondary brain tumor in or adjacent to eloquent brain areas (motor, supplementary motor area [SMA] and language) who are scheduled to undergo tumor resection
Patients with no previous therapy other than biopsy or surgical resection of the primary tumor; patients can have received pre-operative radiation to the primary tumor site, but cannot have received radiation directly to, or in close approximation of, the lymph node basin
Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura) with the intent to treat or biopsy by surgery as standard of care. Tumor must be >= 2 cm
At least one suspected soft tissue sarcoma tumor that is considered by the investigator to be: (1) accessible for percutaneous injection and (2) at least 2.5 cm in shortest dimension for patients undergoing an incisional biopsy, or at least 3 cm in shortest dimension for patients undergoing an excisional biopsy/tumor resection. Tumors should not be selected if the Investigator believes them to be necrotic or exhibit signs of radiation-induced fibrosis.
Tumor judged to be suitable for open cranial resection based on preoperative imaging studies
Radiotherapy of brain tumor within 3 months before enrollment
A superficial tumor easily and safely accessible for a research biopsy or are being considered for resection or biopsy of their tumor as part of standard of care and have recent pathology
Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies
Tumor accessible to biopsy
BRAF V600E mutation detected in the primary tumor or the recurrent/persistent tumor
Are willing to provide available pre-existing diagnostic or resected tumor samples. Providing fresh tumor biopsies are optional for all subjects in Dose Escalation cohorts. In the Dose Expansion cohort, up to 6 subjects may be requested to provide pre- and post-treatment tumor biopsies based on eligibility for the procedure. For those subjects who do not have an MMR status, inclusion in the Dose Escalation and Dose Expansion can be achieved by providing a fresh tumor biopsy for MMR testing.
Willing to undergo 1 baseline and 1 posttreatment tumor biopsy procedure.
Have a confirmed diagnosis of advanced, refractory solid tumors and tumor progression or treatment intolerance to at least 1 prior therapy.
Patients must have a potential germline mutation, as determined by the NCI-MATCH tumor profiling assay
Patients must have malignant bowel obstruction due to an intra-abdominal primary cancer (i.e. gastrointestinal [GI], pancreas, ovarian, uterine, cervical, kidney, bladder, prostate, gastrointestinal stromal tumor [GIST] [all sites], and sarcoma); patients may still have primary tumor as long as it is not a primary large bowel obstruction from colorectal cancer
Newly diagnosed breast tumor, female genital system tumor, colorectal tumor, and/or lymphoma/myeloma
Gross tumor volume (GTV) or resection cavity must be visible on CT such that it can be delineated as a target for radiotherapy
Diagnosed with primary or metastatic tumor < 5 cm located in peripheral lung
Primary or metastatic lung tumor located in central lung or near vertebral body
Tumor invades a major blood vessel
Tumor treated with PDT within the last 3 months
For participants enrolled in the expansion cohorts in which tumor biopsies are obtained:
Criteria 5, Metastatic liver lesions for injection must be without necrosis (dead tissue )and must be be located where any tumor swelling will not lead to gall bladder tract obstruction or lead to bleeding risk
Gastrointestinal stromal tumor (GIST).
A tumor with direct extension to the chest wall and/or to the skin.
Solid Tumor analyzed by Caris Molecular Intelligence™ Service Profile(s) and/or Caris\n             Next-Generation Sequencing
Subject must be candidate for intralesional therapy administration defined as one or more of the following: i. at least 1 injectable cutaneous, subcutaneous, or nodal SCCHN tumor ? 10 mm in longest diameter ii. multiple injectable cutaneous, subcutaneous, or nodal SCCHN tumors that in aggregate have a longest diameter of ? 10 mm Note: Mucosal surfaces of tumor lesions and visceral metastases should not be injected.
Subject at risk of airway compromise in the event of postinjection tumor swelling/inflammation based on investigator judgment.
Subjects with tumor that directly contacts or encases a major blood vessel AND there is ulceration and/or fungation onto the skin surface
For TAK-580 + nivolumab and TAK-202 (plozalizumab) + nivolumab only: Had disease accessible for repeat nonsignificant risk biopsy (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures extending beyond the esophagus, stomach, or bowel) and willingness to undergo serial tumor biopsies.
Scheduled for a lumpectomy of a breast tumor.
The test to confirm ALK-positivity may be performed in archival tumor (obtained at or since the time of diagnosis), or in a newly obtained tumor sample taken prior to the first day of study drug. Results confirming ALK-positive status must be available before initiating treatment with ceritinib.
Confirmed advanced solid tumor or hematologic malignancy
anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and
Subject must consent to pretreatment and on treatment tumor biopsies
For Concomitant Treatment: Prior tumor resection or biopsy up to 8 weeks prior to first MRZ dose
Other chemotherapy or anti-tumor treatment for brain tumor (other than therapies required by the inclusion criteria of this protocol)
Subjects must have a tumor lesion that is amenable to an image-guided core biopsy and willingness to undergo two biopsies (baseline and 6 weeks after first dose of study treatment).
Total serum bilirubin ? 1.5 x ULN regardless of liver involvement secondary to tumor. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
Safely accessible tumor lesions (based on investigator's assessment) for serial pre treatment and post treatment biopsies are required for participants receiving TAK-659 monotherapy run-in treatment for 2 weeks followed by TAK-659 plus nivolumab combination treatment [ approximately 10/30 response-evaluable participants]; adequate, newly obtained, core or excisional biopsy of a metastatic tumor lesion not previously irradiated is required. Mandatory biopsies will be taken before TAK-659 monotherapy, after the 2 weeks of TAK-659 monotherapy, and after 6 weeks of TAK-659 plus nivolumab combination therapy. An optional biopsy may be taken at PD with additional consent from the participants.
Safely accessible tumor lesions (based on investigator's assessment) for serial pretreatment and posttreatment biopsies are required for participants receiving TAK-659 monotherapy run-in treatment for 2 weeks followed by TAK-659 plus nivolumab combination treatment (approximately10/30 response-evaluable participants); adequate, newly obtained, core or excisional biopsy of a metastatic tumor lesion not previously irradiated is required. Mandatory biopsies will be taken before TAK-659 monotherapy, after the 2 weeks of TAK-659 monotherapy, and after 6 weeks of TAK-659 plus nivolumab combination therapy. An optional biopsy may be taken at progression with additional consent from the participants.
Safely accessible tumor lesions (based on investigator's assessment) for serial pretreatment and posttreatment biopsies are required for participants receiving TAK-659 monotherapy run-in treatment for 2 weeks followed by TAK-659 plus nivolumab combination treatment (approximately 10/30 response-evaluable participants); adequate, newly obtained, core or excisional biopsy of a metastatic tumor lesion not previously irradiated is required. Mandatory biopsies will be taken before TAK-659 monotherapy, after the 2 weeks of TAK-659 monotherapy, and TAK-659 after 6 weeks of TAK-659 plus nivolumab combination therapy. An optional biopsy may be taken at progression with additional consent from the participants.
For dose expansion participants who will have tumor biopsies collected:
DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment. Positive is defined as staining in ?75% of tumor cells.
Has provided recently or newly obtained core or excisional biopsy from a locally recurrent inoperable or metastatic tumor lesion for central determination of TNBC status and PD-L1 expression, unless contraindicated due to site inaccessibility and/or participant safety concerns.
Tumor must harbor an IDH1-R132X mutation
Patients in the expansion cohort undergoing tumor biopsies may not be on anticoagulants
Confirmed HER2 overexpression or gene-amplified tumor
Histological or cytological documentation of an advanced solid tumor
The patient's tumor has been evaluated and prospectively identified as having FGFR 1, 2, 3, or 4 genetic alterations.