Patients who have gross residual disease or distant metastatic disease
Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue are eligible for this study; note:* For the purpose of this study, chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology or ipsilateral pleural based secondary tumor nodules will be considered localized disease* Patients with regional node involvement, based on clinical suspicion confirmed by pathologic documentation are considered to be non-metastatic* Patients with discontinuous osseous lesions within the same bone are considered to be non-metastatic* Tumors arising in the bony skull (extra-dural) are considered to be extracranial
Patients must have no evidence of metastatic disease; metastatic disease:* Are lesions which are discontinuous from the primary tumor, are not regional lymph nodes and do not share a body cavity with the primary tumor; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be taken* Skeletal lesions in adjacent bones (trans-articular)* Contralateral pleural effusion and contralateral pleural nodules* Distant lymph node involvement* Patients with pulmonary nodules are considered to have metastatic disease if the patient has:** Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied and negative for Ewing's** Biopsies of solitary nodule =< 0.5 cm or multiple nodules =< 0.3 cm are not required but if performed and positive indicate metastatic disease
Patients must not have inflammatory breast cancer and must not have metastatic disease
HCC patients only:* First line (i.e., no prior systemic therapy) or second-line (with prior first-line sorafenib therapy only) advanced HCC * Child Pugh class A or B7 liver disease * Prior chemoembolization, radioembolization, radiofrequency ablation (RFA), or other local ablative therapies are permissible if >= 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable (Phase I)
Cytological or histological confirmed diagnosis of hepatocellular carcinoma that is locally advanced or metastatic and is not amenable to treatment with surgery or to orthotopic liver transplant (Phase II)
Prior chemoembolization, radioembolization, radiofrequency ablation (RFA) or other local ablative therapies are permissible if >= 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable
Clinical or radiographic evidence of metastatic disease
Presence of residual or recurrent cancer (locally or metastatic)
For Part I (Arms A, B): Patients can have either locally advanced or metastatic pancreas adenocarcinoma for which no prior therapy has been administered for either locally advanced or metastatic disease; prior adjuvant therapy is permissible if gemcitabine or a fluoropyrimidine was administered with or without radiation and if disease recurrence has been documented at least 6 months after completion of adjuvant therapy
For Part II (Arm C): Patients can have either locally advanced or metastatic pancreas adenocarcinoma; up to two prior treatment regimens are permissible (excluding a prior PARP inhibitor) for either localized or metastatic pancreas adenocarcinoma; prior combined chemotherapy and radiotherapy is permissible provided the patient has measurable disease outside the radiation port; prior therapy must have been completed at least 3 weeks prior to starting study therapy
Patients with metastatic disease by cranial or spinal MRI evaluation or CSF cytology (unless medically contraindicated) are not eligible
Patients must have a diagnosis of metastatic melanoma which is measurable either clinically or radiologically
Patients with a history metastatic melanoma involving the brain will be excluded if they have active disease or have had active disease within the prior six months that was not controlled with surgery or radiotherapy
Definitive clinical or radiologic evidence of metastatic disease
Clinical or radiographic evidence of metastatic disease; metastatic workup is not required, but is recommended for patients with clinical stage III disease; Note: isolated ipsilateral supraclavicular node involvement is permitted
Patients with breast cancer must have had at least one prior chemotherapy regimen for metastatic disease; additionally, patients with breast cancer must have received prior tamoxifen and/or aromatase inhibitor therapy (if post-menopausal) with at least one hormonal regimen in the metastatic setting; patients with HER2+ breast cancer must have progressed after at least one prior HER2-directed regimen (trastuzumab, lapatinib) for metastatic disease* All other patients must have disease that has progressed following at least one line of standard therapy; prior therapy with tamoxifen is allowed
Patients with newly diagnosed, unresectable, metastatic, and measurable ASPS who show clinical evidence of disease progression (including history and increasing physical symptoms) will also be eligible; on-study documentation will include a physician�s rationale that supports evidence of clinical disease progression (i.e., increasing tumor pain)
Patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery
Patients must not have evidence of metastatic tumor or other cancer
Have stable metastatic pancreatic cancer after receiving 8-12 doses of FOLFIRINOX (measurable disease is not required)
Patients who have had prior chemotherapy for metastatic pancreatic cancer (other than FOLFIRINOX); prior radiation is allowed; chemotherapy for non-metastatic disease is allowed
Chest x-ray negative for metastatic disease
Patients must have metastatic disease or locally advanced unresectable disease
Metastatic breast cancer (MBC) OR metastatic non-small cell lung cancer (NSCLC) OR metastatic adenocarcinoma of the prostate; the sites of allowed metastases are: peripheral lung, central lung, mediastinal/cervical lymph node, liver, spinal/paraspinal, osseous, and abdominal-pelvic* NOTE: after the required number of evaluable patients have been accrued for a given dose level, the accrual for that metastatic location will be temporarily suspended while the safety of that dose level is assessed; a patient can only be entered onto the trial if all of their metastatic locations are open to accrual (e.g. if central lung is temporarily suspended for safety assessment and the patient has a central lung metastases, regardless of other metastases, they cannot enroll until the safety of dose to central lung is determined)
Extent of disease:* Patients with non-metastatic and metastatic disease are eligible* Initially unresectable patients, with or without metastatic disease, are eligible as long as there is a commitment at enrollment to resect the primary tumor
Baseline chest computed tomography (CT) with or without contrast must be performed within 6 months (180 days) prior to randomization to ensure no evidence of disease; if clinically indicated additional imaging studies must be performed to rule out metastatic disease
No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 years prior to registration
Patients must have melanoma that is metastatic and clearly progressive on prior therapy
Prior palliative radiation treatment for metastatic disease to be treated on the protocol (including radiopharmaceuticals)
Metastatic or unresectable locally advanced
No more than two prior therapies for metastatic disease
Patients in the phase I portion must have:* Histologically confirmed diagnosis of metastatic, genitourinary solid tumor* Metastatic disease defined as new or progressive lesions on cross-sectional imaging; patients must have at least:** One evaluable site of disease ** Or, appearance of one new bone lesion
Progressive cancer (must be considered no evidence of disease or stable)
Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 90 days prior to randomization
Locally advanced/unresectable or metastatic disease
Re-registration: locally advanced/unresectable or metastatic disease
Patient must NOT have human epidermal growth factor-2 positive (HER2+) metastatic disease
Patient must NOT have received prior endocrine therapy for metastatic disease (i.e., must be first-line endocrine therapy for metastatic disease)
Patients with M1 disease or a history of M1 disease
Cohort 2 patients must have had a complete resection of all sites of metastatic disease within 30 days prior to enrollment* Patients will only be eligible after they have undergone complete surgical resection of suspected metastatic disease that is histopathologically confirmed to be osteosarcoma prior to enrollment** Note: the definition of complete resections is: gross resection of all disease as per the operating surgeon; post-operative imaging is not required for confirmation of complete resection* Patients must undergo resection of any lung lesion meeting criteria for likely metastatic disease, defined as: ** 3 or more lesions > 5 mm in diameter OR a single lesion > 1 cm* Patients with lung as the only site of resected metastatic disease must have refused participation in protocol AOST1421** Note: this applies if AOST1421 is open to enrollment at the enrolling institution on the day the patient consents
Patients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma that is either known or suspected to be of gastrointestinal (GI) origin; primary tumors arising from the lung, gynecologic organs or prostate are not permitted
Dose expansion: patients must have histologically or cytologically confirmed invasive adenocarcinoma of the breast (human epidermal growth factor receptor 2 [HER2]-negative) that is locally advanced/metastatic and has progressed despite standard therapy; at least 1 prior chemotherapy regimen in the metastatic setting, and two lines of hormonal therapy (administered in the adjuvant or metastatic setting) for patients with hormone receptor-positive disease; NOTE: HER2-negativity will be defined per American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines; patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell are not eligible
Patients with current local, loco-regional relapse and/or distant metastatic breast cancer
No prior cytotoxic chemotherapy for metastatic disease; prior immunotherapy is permitted
Locally advanced/unresectable (as determined by local surgeon) OR metastatic disease
Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib); if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic renal cell carcinoma (RCC); if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients may have also received prior immunotherapy; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration
Non-small cell lung cancer (NSCLC)* Metastatic or locally advanced disease that progressed after at least one prior therapy * Note: patients who have actionable molecular targets (e.g., epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], c-ros oncogene 1[ROS1] mutations) must have received (when indicated) prior appropriate targeted therapy using Food and Drug Administration (FDA)-approved agents
Patients must have had =< 1 prior cytotoxic regimen for metastatic disease (unless enrolling in the Progressive Brain Metastases Cohort); note that endocrine and immunotherapies do not count as cytotoxic regimens
Baseline chest computed tomography (CT) must be performed within 1 month (30 days) of randomization to ensure no evidence of disease; if clinically indicated, additional imaging studies must be performed to rule out metastatic disease
Locally advanced or metastatic disease; locally advanced disease is defined as disease not amenable to local therapy such as surgery and/or radiation
Patients must have had one and only one prior regimen of systemic therapy for metastatic disease unless the patient meets the criteria below
Prior systemic therapy and chemoradiotherapy for treatment of resectable, borderline resectable or locally advanced unresectable disease is allowed and does not count toward prior therapy for metastatic disease
Patients who received systemic therapy with gemcitabine/nab-paclitaxel for resectable or borderline/locally advanced unresectable disease and progressed with metastatic disease within 3 months of the past dose of systemic therapy are eligible
Patients must have a current diagnosis of breast cancer, non-small cell lung cancer, or colorectal cancer; the current diagnosis may be an initial diagnosis or recurrence and/or progression of previously diagnosed disease; cancer may be metastatic or non-metastatic
Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis demonstrating no evidence of nodal involvement or metastatic disease (magnetic resonance imaging [MRI] or computed tomography [CT] scan) within 90 days prior to registration; patients with T1 disease must have re-resection confirming =< T1 disease within 90 days prior to registration
Definitive clinical or radiologic evidence of metastatic disease
Have recurrent or refractory/unresectable disease for which there is no known curative therapy* Wild type-GIST: patients with recurrent or progressive disease will be eligible; newly diagnosed patients with resectable localized disease will not be eligible; newly diagnosed patients with metastatic disease and newly diagnosed patients with residual tumor following surgical debulking will be eligible* PHEO/PGL: patients with recurrent or progressive disease will be eligible; newly diagnosed patients with PHEO/PGL that is metastatic at diagnosis and/or unresectable will be eligible; patients with PHEO/PGL with localized (non-metastatic), resectable disease will not be eligible* Renal cell cancer associated with HLRCC: patients with localized, resectable HLRCC-associated renal cell cancer will not be eligible; patients with metastatic and/or unresectable HLRCC-associated renal cell cancer will be eligible
Patients must have measurable disease at baseline and 3 or fewer discrete, extracranial metastatic disease sites that are technically amenable to stereotactic body radiation therapy (SBRT) or resection (at least one disease site must be amenable to radiation); some examples of what constitutes specific radiation treatment sites defining distinct metastatic disease sites are as follows: a) A lesion in each adrenal gland represents 2 of 3 sites of metastatic disease allowed to be treated on protocol; b) Similarly to NRG study RTOG 0631, disease in 2 contiguous vertebral bodies (with up to 6 cm of paraspinal extension) can represent one site of disease in the spine; non-contiguous lesions in vertebral bodies separated by one vertebral body free of disease should be viewed as 2 sites of treatment; and c) Two lesions in such close proximity to one another that treatment with one isocenter is more accurate and safer in the liver, lungs, or other similar anatomic locations should be viewed as one site of metastatic disease treatment.
For de novo stage IV NSCLC patients (patients with metastatic disease at first presentation), primary disease must be treatable with local therapy in the form of SBRT or hypofractionated radiation. If the primary disease is found in the peripheral or central lung parenchyma without nodal disease, for instance, SBRT may be employed at the discretion of the treating institution. If primary disease is more advanced with involvement of the mediastinum (T4 tumor, N1-N3 disease, etc.), these volumes should be technically treatable with hypofractionated radiation; surgery should only be used for metastatic tumors that can be completely resected by lobectomy, segmentectomy, or wide wedge resection.
At least one site of metastatic disease or primary disease must be determined by radiation oncologist to be treatable with radiation.
Metastatic disease invading the esophagus, stomach, intestines, or mesenteric lymph nodes if not a candidate for surgery for these lesions.
Patients with more than 3 discrete locations of extra-cranial metastatic disease after first-line systemic therapy requiring more than 3 radiation/surgery plans to cover these distinct metastatic disease entities.
Subjects must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two planes* This disease must be located primarily in the supratentorial region* Patients with significant disease that is metastatic outside of the supratentorial region are ineligible
Patients for who clinical suspicion is present of metastatic disease in the cerebrospinal fluid (CSF) or spine must have magnetic resonance imaging (MRI) of spine and CSF obtained (lumbar puncture or through Ommaya, external ventricular drain [EVD] or shunt) with negative cytology; patients with CSF that is positive for tumor cells or metastatic disease found on MRI are ineligible
Definitive clinical or radiologic evidence of metastatic disease
Patients with newly diagnosed, unresectable, metastatic and measurable ASPS will also be eligible if they show clinical evidence of disease progression (including history and increasing physical symptoms); on-study documentation will include a physician�s rationale that supports evidence of clinical disease progression (i.e., increasing tumor pain)
Patients must have a histologically or cytologically confirmed measurable GIST without platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) or KIT proto-oncogene receptor tyrosine kinase (KIT) mutations; GIST may be newly diagnosed or recurrent provided that it meets criteria for progressive or metastatic disease; metastatic disease refers to disease outside the gastrointestinal (GI) tract, not simply a multifocal primary tumor; testing performed by the Laboratory of Pathology, National Cancer Institute (NCI), unless previously conducted by a CLIA/College of American Pathologists (CAP) external laboratory; analysis will include evaluation of 4 exons of KIT (9, 11, 13, 17) and 3 exons of PDGFRA (12, 14, 18)
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
Known metastatic disease
No evidence of residual involved lymph node disease or metastatic disease at the time of registration based on clinician assessment of imaging; the treating physician will determine if incidental lesions on imaging require workup to exclude metastatic disease; if based on review of images, the treating physician determines the patient to be stage III, then the patient is eligible
Patients with metastatic disease
Patients must not have metastatic disease (i.e., must be M0); patients must not have locally recurrent disease
Definitive evidence of metastatic meningioma
Patients with metastatic disease
Definitive clinical or radiologic evidence of metastatic disease; if applicable
Definitive evidence of multifocal disease