Have non-epithelial ovarian tumors (e.g., germ cell tumors, sex cord stromal tumors)
Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study.
Patients that do not qualify for one of the histologic cohorts may be considered for registration in the “Not Otherwise Categorized” Rare Tumors cohort with confirmation of at least one of the study chairs via email
Clinical T4 tumors
Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN protocol
Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C); tumors must be deemed to originate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve)
Patients with grade 1 NRSTS tumors of any size are not eligible
Patients with MYCN amplified tumors are not eligible
Patients must have had all grossly visible papillary tumors removed within 30 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 30 days prior to registration
Ewing's family of tumors (EFTs)
For Phase 1b, must have advanced refractory solid tumors in any line of therapy.
Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups:
Rare Tumors:
COHORT A: Patients with newly diagnosed, previously untreated primary tumors that present with brain metastases should not forego available therapy that has demonstrated a definitive overall survival benefit as first line therapy for metastatic disease; therefore, in cases of previously untreated systemic solid tumors only those patients for whom there is no available therapy with definitive overall survival benefit, those that have failed at least one line of prior therapy for their primary tumor, or those refusing standard therapy will be eligible for this study; specifically, for patients with previously untreated primary tumors, the following diagnoses will be excluded: HER2-positive breast cancer; small cell lung cancer; non-small cell lung carcinoma (NSCLC) with targetable genomic tumor aberrations (e.g. EGFR, ALK)
Carcinoid tumors of any site are eligible; patients with pancreatic neuroendocrine tumors are excluded
Patients with histologically or serologically confirmed relapsed/refractory nonseminoma germ cell tumor, (i.e., embryonal carcinoma, choriocarcinoma, or yolk sac tumors) including female germ cell tumors (GCT) and primary mediastinal NSGCT
Any solid tumors with masses that are accessible without imaging
Subjects with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, and subjects with tumors that carry a poor prognosis and have no known standard curative therapy are eligible;\r\n* Brain tumors of all World Health Organization (WHO) grades except diffuse intrinsic pontine glioma (DIPG); patients with DIPG are not eligible\r\n* Extracranial solid tumors including histiocytoses (e.g. Langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma)
Prior consent to have tumors used for unspecified future research
Subjects must have measurable disease by RECIST 1.1 criteria including one target tumor for injection. Superficial tumors must have one tumor greater than or equal to 1.0 cm, deep tumors greater than or equal to 1.0 cm (as measured by caliper (for non-injected tumors only) or image guidance);
Subjects must have a minimum of one injectable lesion as determined by the investigator (for superficial tumors) or radiologist (deep tumors).
Tumors whose proximal end are higher that the level of the carina
Cumulative volume of all tumors ? 15 cc
Neuronal tumors \r\n* Ganglioglioma (excluding tumors with anaplastic astrocytic components) \r\n* Infantile desmoplastic ganglioglioma
Patients with subependymal giant cell astrocytomas are excluded; patients with intrinsic brain stem tumors of the pons will be excluded from the study
Endometrial Carcinoma (sarcomas and mesenchymal tumors are excluded)
Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded)
Advanced solid tumors
At least one site of measurable disease in subjects with solid tumors and NHL.
High grade, rapidly proliferative solid tumors (eg, small cell lung cancer, germ cell tumors, neuroblastoma) with extensive tumor burden.
Patients with low grade gliomas and Rb1 negative tumors
Patients with sessile appearing tumors, which may be invasive or high-grade
In addition to having AR+ tumors, patients must fit into 1 of the 2 following categories:
Both peripheral and central tumors are accepted for this trial
IO therapy resistant or insensitive tumors
Necrotic tumors or tumors close to large blood vessels that may impose an increased bleeding risk when treated with anti-VEGF agents.
Infratentorial tumors
T1 to T2a tumors OR T3 tumors smaller than 7 cm invading the mediastinal or pericardial pleura are also eligible for this protocol as long as normal tissue dose constraints can be met
Regimen A only (monotherapy): Subjects with advanced metastatic solid tumors
Phase 2a: Patients with various solid tumors or NHL who have received prior therapy.
Advanced solid tumors
Have Karnofsky score ?40 at enrollment (not applicable for subjects with benign bone tumors)
Phase 1: Participants must be diagnosed with histologically confirmed solid tumors (excluding CNS tumors), which is relapsed or refractory, and for which there are no currently available therapies.
Patients with secreting tumors must be receiving pharmacologic catecholamine blockade
T4 tumors with involvement of any adjacent structure, including the trachea, aorta or pleura
Patients with tumors that cannot be measured or clinically followed
Patients with tumors > 7 cm or tumors involving the main bronchus or associated vessels or tumors that invade any critical structures (such as esophagus, brachial plexus, heart, mediastinal major vessels) are not suitable for SABR
Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord, tumors extending into or crossing the corpus callosum, intraventricular tumors, pineal tumors, pituitary tumors, radiological evidence of active (growing) multifocal disease, leptomeningeal disease, or other locations at the discretion of the treating neurosurgeon
Patients with progression of multifocal tumors or tumors involving the posterior fossa (brainstem and cerebellum) will be excluded, as will patients where the anticipated treatment margin will be within 5 mm of critical intracranial structures (e.g., primary branches of cerebral vessels, dural sinuses, hypophysis or cranial nerves).
For subjects enrolled for “major deformity” or a “significantly disfiguring” tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments; in order to enroll a plexiform neurofibroma for these indications, the Study Chair or Co-Chair must be contacted to review patient eligibility prior to enrollment
Accessible tumors for sequential biopsies
Tumors must be potentially surgically resectable via a transoral approach, at the discretion of the treating surgeon
non-hilar tumors
Primary tumors of radiosensitive histology (lymphoma, multiple myeloma, small cell carcinoma, germ cell tumors), as conventional radiation is likely to be effective in such cases
Patients may have single or multinodular tumors
Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors
Patients must have histologically confirmed advanced RCC (any histology); collecting duct tumors and tumors originating from the renal pelvis or upper urinary tract are considered of urothelial origin and are excluded from this protocol
Subjects must have measurable liver tumors that are suitable for injection.
Tumors involving the cerebellum
Only MUC16^ecto tumors with moderate to strong immunoreactive scores (3-5) will be considered positive
Patients whose tumors are positive for the sensitizing ROS-1 fusion
Patients must have untreated or relapsed SCCS that is considered to be aggressive and locally advanced by the following criteria: tumors 2 cm or more, tumors invading deep tissues such as muscle, cartilage or bone; tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes; patients may have had prior surgical interventions or been treated with investigational agents with residual or recurrent disease
Patients with primary tumors located at or above the carina
Surgery achieves either no gross residual disease or optimal cytoreductive status defined as no single lesion measuring more than 1 cm in its greatest diameter (this protocol calls for the intentional delay in resection of up to 3 tumors per patient until the HIPEC procedure is complete; the surgeon will identify these tumors as easily resectable from a technical and safety aspect)
Patients with tumors primarily of the tail of the pancreas requiring a distal pancreaticoduodenectomy would be excluded; tumors of the body that require a surgical approach similar to pancreatic head tumors are acceptable
Infratentorial and multi-focal tumors are eligible
Tumors infiltrate the cerebellum, bilateral corpus callosum (“butterfly glioma”), ventricular system, or brain stem
Patients must have a confirmed histopathologic diagnosis and be classified as high risk defined by having an expected survival of < 10%; examples include:\r\n* Neuroblastoma or ganglioneuroblastoma\r\n** Failure to achieve at least a partial response (PR) after induction therapy with Children’s Oncology Group (COG) ANBL0532 or standard chemotherapy\r\n** Refractory to induction chemotherapy with COG ANBL0532 or standard chemotherapy\r\n** Patients with high risk disease whose autologous peripheral blood stem cell product is contaminated with neuroblastoma or who do not have an autologous product available\r\n** Patients with high risk disease who do not meet eligibility requirements/organ function requirements for myeloablative conditioning\r\n** Patients with >= 5 identified lesions on the end of induction (COG ANBL0532 or standard chemotherapy) meta-iodobenzylguanidine (MIBG) scan \r\n* Stage 4 rhabdomyosarcoma\r\n* Metastatic Ewing sarcoma\r\n* Osteosarcoma with metastatic disease beyond the lungs and/or with lung metastases not amenable to resection\r\n* Hepatoblastoma not amenable to resection\r\n* Metastatic melanoma\r\n* Desmoplastic small round cell tumor\r\n* Brain tumors such as astrocytic tumors, oligodendroglial tumors, ependymal tumors, choroid plexus tumors, other neuroepithelial tumors, neuronal and mixed neuronal-glial tumors, tumors of the pineal region, embryonic tumors\r\n* Any other solid tumor and soft tissue sarcoma with an estimated < 10% chance of survival will be considered on a case by case basis at the departmental tumor board and/or sarcoma meeting
Biliary strictures caused by confirmed benign tumors
For tumors that are invasive, HER2 must be performed (positive or negative is acceptable).
Patients with advanced malignant hepatic tumors.
Patients with measurable inoperable, histologically confirmed primary lung and esophageal carcinomas, thymic neoplasms, germ cell tumors, malignant pleural mesotheliomas or chest wall sarcomas, as well as patients with gastric, colorectal or renal cancers and sarcomas metastatic to the thorax are eligible
All patients with histologic proof of advanced solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority
WHO grade I: tumor that are newly diagnosed and tumors that are incompletely excised; tumors that have recurred post resection
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)
For tumors other than DSRCT, 8H9 reactivity must be confirmed by immunohistochemistry
Pure sarcomas or borderline tumors or mucinous tumors
Group 2: NRAS or HRAS mutant solid tumors(Part B)
Patients whose tumors harbor a ROS1 rearrangement must have demonstrated progression on or intolerance to crizotinib
More than 3 metastatic tumors
Subjects must not have tumors adjacent to vital structures such as carotid arteries.
At least two BCC tumors, preferably more; these tumors must be located in different body regions or alternatively, located > 10 cm apart at sites that can be reproducibly separated into red and blue illumination fields
THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: Tumors do not engraft in the mice or do not respond to any of the selected agents.
Patients with tumors that score negative in the in vitro organoid bio-assay will be excluded
Patients with non-melanoma skin cancers (NMSC) must have advanced or refractory tumors\r\n* Advanced/unresectable is defined by at least 1 of the following criteria: tumors 2 cm or more, tumors considered unresectable, tumors invading deep tissues such as muscle, cartilage or bone, tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes and/or distant sites\r\n* Refractory is defined by persistent or recurrent tumor despite prior therapy consisting of at least 1 of the following: surgery, radiation therapy, intralesional therapy, topical therapy, or systemic therapy
Multiple (? 2) separate enhancing tumors
tumors encasing major vascular structures (i.e., carotid artery or tumors close to other vital organs), are not considered appropriate
Tumors in which the invasive component is present only as micro-invasion
Patients with grade 1 non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) tumors of any size are not eligible
Assessment of GD2 status is not required for NB or for other tumors known to express GD2 in 70% or more of cases: specifically osteosarcoma (GD2 expressed in 88%), spindle cell sarcoma (93%) and desmoplastic small round cell tumor (DSRCT) (70%); all other non-NB tumors will require confirmation of GD2 expression on cell surface by immunohistochemistry on fresh frozen tissue that will be performed at MSKCC; patients with suspected GD2-positive tumors (other than osteosarcoma, spindle cell sarcoma or DSRCT) will have their tumors assessed after obtaining a separate informed consent for this purpose
Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not eligible
Patients with histologically confirmed unresectable or metastatic pancreatic (p)NETs of low or intermediate grade; high-grade tumors or tumors with small cell histology will be excluded (Part 2)
Patients with histologically or cytologically proven lung or esophageal cancers, thymic or mediastinal germ cell tumors, malignant pleural mesotheliomas, or primary thoracic sarcomas, as well as patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura that have no clinical evidence of active disease (NED) or minimal residual disease (MRD) not readily accessible by non-invasive biopsy or resection/radiation following standard therapy
Histologically proven malignant solid tumors with measurable disease (except lymphomas)
Tumors must have a Ki-67 index greater than 20% and/or > 20 mitotic figures/10 high-power fields
Patients with advanced malignant solid tumors are excluded
Patients with carcinoid tumors
Selected tumors with rhabdoid features
Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
Cohort 2 - MRT/RTK/selected tumors with rhabdoid features
Cohort 3 - INI-negative tumors:
Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
For subjects with INI1-negative tumors only - have the following test results available:
Morphology and immunophenotypic panel consistent with INI1-negative tumors, and
Phase I (Cohort X): Participants with PIK3CA-mutant tumors and measurable disease per RECIST v1.1
Phase 1: Subjects with advanced or metastatic solid tumors.
Patients with bilateral renal tumors are eligible provided both tumors have undergone full surgical resection and at least one of the tumors meets all eligibility criteria; patients must plan to start study drug within 84 days after the date of the resection of the first tumor
Inaccessible tumors or for whom biopsy is contraindicated
Patients with non-adenocarcinomas, adenosquamous carcinomas, islet cell (neuroendocrine) tumors, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas; patients with tumors that are largely IPMN with a minimal or minor component of invasive carcinoma are not eligible; patients with acinar carcinomas are not eligible; patients with IPMN’s that contain some secondary (minor) foci of adenocarcinoma are also not eligible
Individuals with inaccessible tumors or for whom biopsy is contraindicated
Presence of advanced malignant hepatic tumors.
Prior nasopharyngeal cancer, salivary gland or sinus tumors.
Documented IDH1R132-mutant tumors
Metastatic or inoperable solid tumors* (except gastrointestinal tumors or tumors that originated or metastasized to the liver) for which no standard treatment exists, or have progressed or recurred following prior therapy.
Patients with metastatic malignant solid tumors who received treatment in the past 6 months are excluded
Patients who have uterine sarcomas, carcinosarcomas, serous tumors (any component) or pure clear cell carcinomas.
Any patients with infratentorial tumors
Periampullary tumors
Locally advanced tumors at diagnosis (T4), including tumors fixed to the chest wall, peau d’orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid)
Tumors involving the cerebellum
Have recurrent or metastatic solid tumors
Tumors with involvement of the mediastinum.
For subjects enrolled for a “major deformity” or “significantly disfiguring” tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments; in order to enroll a plexiform neurofibroma for these indications, the study chair or co-chair must be contacted to review subject eligibility prior to enrollment
Patients with advanced malignant solid tumors are excluded
Patients with advanced malignant hepatic tumors (metastasis)
other solid tumors (all comers) for which there is no standard systemic therapy and there is a rationale for use of pexidartinib at the Investigator's discretion
Recurrent or refractory solid tumors
Technically resectable, single tumors of any size, tumors with satellite nodules within 2 cm of the primary tumor that are resectable; limited and resectable multi- focal disease (less than 4 tumors technically resectable)
VS or meningioma surgery determined clinically necessary by the treating physician; similar cerebellopontine (CP) angle schwannomas, such as facial nerve schwannomas and “collision tumors”, i.e. tumors arising from multiple cranial nerves, are eligible
Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d’orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
Borderline resectable- Tumors considered borderline resectable are defined as follows:
T0 tumors
Patients with cystoscopically detected bladder tumors requiring TURBT
Patients with bladder tumors which are endoscopically resectable by surgeon’s judgment with only one trip into the operating room
Patients with advanced malignant hepatic tumors
Patients with centrally-located pulmonary or mediastinal primary tumors or metastases adjacent to or invading large blood vessels
Tumors poorly visualized by x-ray mammography or ultrasound imaging
Tumors measuring greater than 20mm in diameter
Cavitary tumors or tumors invading or abutting large blood vessels.
Tumors must be supratentorially located
Patients with advanced malignant hepatic tumors
Concurrent metastatic solid tumors
Patients with primary supraglottic tumors that involve the true larynx
Detectable AR-V7 from circulating tumors (CTCs)
Borderline resectable- Tumors considered borderline resectable are defined as follows:
Metastatic and/or locally advanced malignant solid tumors enriched in tumor types known to be mesothelin expressing
Based on the results of the mutation test, lymphoma subjects may be enrolled in one of four cohorts: GCB-DLBCL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. GCB-DLBCL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort. tFL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. tFL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort
Patients who have benign or malignant soft tissue tumors of the extremities, flanks, pelvis, or shoulders that require surgical intervention
Index tumor involves the skull (treatment of other painful tumors in subjects with skull tumors is not excluded)
Patients who do not have pure uterine sarcomas (i.e., no mixed malignant Mullerian tumors).
Patients with advanced malignant solid tumors
Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors
Tumors that are invading a major vessel; NSCLC tumors abutting to a major vessel
Tumors of the lips, sinuses, salivary glands or nasopharynx.
Cavitary tumors or tumors invading or abutting large blood vessels
Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy
Evidence of HER2 oncoprotein expression at the 2+ level by central laboratory. Patients whose tumors exhibit 2+ staining by IHC are eligible for the study.
Patients whose tumors score 1+ by conventional IHC, are non-amplified by FISH testing, and whose tumors score > or = 10.5 by HERmark® testing, are eligible for the study.
Patients with islet cell tumors or other non-epithelial cell malignancies of the pancreas.
Known advanced malignant hepatic tumors
Subjects with advanced or metastatic solid tumors for whom a chemotherapy regimen is considered appropriate
Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors, primary brain tumors, NF-1 associated PF and LCH. In subjects with brain stem gliomas the requirement for histological confirmation can be waived if a biopsy was not performed. For plexiform neurofibromas, histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiological findings, but should be considered if malignant degeneration of a PN is clinically suspected.
Phase 1: Subjects with advanced or metastatic solid tumors.
Measurable or evaluable disease according to RECIST for solid tumors or according to IWRC for NHL tumors
Patients who have mixed tumors with small-cell elements are ineligible
tumors must be measurable
Have any other functional tumors if they have familial Multiple Endocrine Neoplasia Syndrome 1 or 2 (MEN 1 or MEN 2).
Patients with central tumors within the proximal tree or touching the mediastinal pleura
Patients with infra-tentorial tumors are not eligible
Tumors that are Her2 positive are eligible
TanyN+M0 or T3-4N any M0 tumors
Tumors with significant involvement of the proximal stomach which, in the opinion of the treating thoracic surgeon, would require an esophagogastrectomy
For Part A, participants must have histologically confirmed solid tumors, CNS tumors, or lymphoma based upon biopsy or surgery at initial diagnosis and/or relapse/progression; the only exception to histologic confirmation is for pediatric tumors that are routinely diagnosed exclusively by standard clinical imaging criteria: diffuse intrinsic pontine glioma and optic pathway glioma
Metastatic solid tumors
Infratentorial tumors
Diagnostic categories\r\n* Sarcoma (soft tissue and bone)\r\n* Kidney tumors\r\n* Brain tumors\r\n* Other solid tumors (gonadal and germ cell tumors, retinoblastoma, neuroblastoma, and miscellaneous tumors)\r\n* Hodgkin lymphoma
Subjects must be at the recurrent/metastatic setting, with selected advanced solid tumors.
Benign tumors, neuroendocrine tumors, soft tissue tumors based on preoperative work-up or intraoperative findings
Tumors must be suitable for cryoablation
Index tumor involves the skull (treatment of other painful tumors in subjects with skull tumors is not excluded)
Patients with primary tumors located above the carina
Intracoelomic primary tumors or tumors expected to drain to an intracoelomic SLN
Patient with more than 3 tumors treated with any percutaneous ablation
Adults with intraocular tumors (melanoma, metastasis, retinal tumors) who are going to undergo enucleation diagnosed in the Emory Eye Center Ocular Oncology Service; patients will be assessed by a cardiologist or cardiology fellows
Patients in whom the tumor might not be accessible for peritumoral injection of indocyanine green, e.g. small, central tumors
Patients with known active advanced malignant solid tumors are excluded (except for basal or squamous skin cancers, or carcinomas in situ); patients with additional hematologic malignancies that require treatment are excluded
Tumors of or involving the midline, basal ganglia, or brain stem as assessed by MRI
Patients with T2b tumors or T3 tumors > 5 cm or patients with tumors involving the central chest/structures of the mediastinum
Prior craniotomy for resection of deep seated tumors in thalamus and brain stem
A known other currently active malignancy; (benign tumors and benign polyps, basal cell carcinomas of skin, superficial papillary bladder tumors, and pre-invasive carcinoma of the cervix are permitted)
Tumor tissue or blood collections from patients with benign tumors including but not limited to desmoid tumors, carcinoma in situ, or ongoing complete disease response (CR)
Germ cell tumors (GCTs).
Diffuse tumors or multiple malignant tumors in the breast.
synchronous tumors
Part 1: Subjects with advanced or metastatic solid tumors.
Part 1: Subjects with advanced or metastatic solid tumors
Tumors located in the central chest or other location where bleeding is associated with high morbidity