Patients must have histologically confirmed bone or soft tissue sarcoma by central pathology review\r\n* Patients must have histologically confirmed liposarcoma (LPS) (only dedifferentiated and pleomorphic; well differentiated not eligible), undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma (MFH), or gastrointestinal stromal tumor (GIST)
Patients must have slides available for submission to central pathology review; this review is mandatory prior to registration to confirm eligibility and proper cohort assignment\r\n* HISTOLOGIC COHORT 1: Undifferentiated pleomorphic sarcoma (includes: malignant fibrous histiocytoma, myxofibrosarcoma, high grade sarcoma not otherwise specified [NOS])\r\n* HISTOLOGIC COHORT 2: Leiomyosarcoma (either uterine or extra-uterine)\r\n* HISTOLOGIC COHORT 3: Other (either malignant peripheral nerve sheath tumor or synovial sarcoma); during the phase II portion of the study, enrollment will be limited to maximum of 25 patients in this cohort\r\n** Note that the phase I is limited to the histologic subtypes listed above; since patients will be enrolling onto dose cohorts during the phase I, they will not enroll onto specific histologic cohorts, although the histologic subtype informed will be collected during patient enrollment
Histologic documentation: Eligible patients must have histopathologically confirmed sarcoma of one of the subtypes listed, by central review
One of the following chemosensitive histologies as defined in the World Health Organization (WHO) classification of soft tissue tumors (with some evidence of good response to chemoradiation and of sufficient high risk of metastases, or clear evidence of metastases):\r\n* Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called “undifferentiated soft tissue sarcoma” or “soft tissue sarcoma not otherwise specified [NOS]”)\r\n* Synovial sarcoma\r\n* Angiosarcoma of soft tissue\r\n* Adult fibrosarcoma\r\n* Mesenchymal (extraskeletal) chondrosarcoma\r\n* Leiomyosarcoma\r\n* Liposarcoma (excluding myxoid liposarcoma)\r\n* Undifferentiated pleomorphic sarcoma\r\n* Embryonal sarcoma of the liver
Patients with the following histologies are only eligible for the chemotherapy cohort and cannot enroll on the non-chemotherapy cohort:\r\n* Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called “undifferentiated soft tissue sarcoma” or “soft tissue sarcoma NOS”) in patients < 30 years of age\r\n* Synovial sarcoma\r\n* Embryonal sarcoma of the liver
Patients with any size of grade 2 or 3 of the following “intermediate (rarely metastasizing)” or “malignant” tumors, as defined in the WHO classification of soft tissue tumors for which we have consensus data of chemotherapy-resistance are eligible only for the non-chemotherapy cohort:\r\n* So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell tumor of soft tissues\r\n* Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignant solitary fibrous tumor, inflammatory myofibroblastic tumor, low grade myofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypical myxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma\r\n* Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft part sarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma, ossifying fibromyxoid tumor, myoepithelioma, myoepithelial carcinoma, extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioid cell differentiation (PEComa), intimal sarcoma, atypical fibroxanthoma, mixed tumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoid tumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor\r\n* Chondro-osseous tumors - extraskeletal osteosarcoma\r\n* Pericytic (perivascular) tumors - malignant glomus tumor\r\n* Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignant granular cell tumor, epithelioid malignant peripheral nerve sheath tumor, malignant Triton tumor\r\n* Undifferentiated sarcomas (with a specific pathologic category in the WHO classification) - undifferentiated round cell sarcoma, undifferentiated epithelioid sarcoma, undifferentiated spindle cell sarcoma
Patients with isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) but without evidence of APL by bone marrow or peripheral blood morphology are excluded
Patients must have recurrent or refractory disease, or newly diagnosed disease with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:\r\n* Ewing sarcoma \r\n* Rhabdomyosarcoma (RMS)\r\n* Non-rhabdomyosarcoma soft tissue sarcomas (STS) including microphthalmia transcription factor associated STS (alveolar soft part sarcoma [ASPS] and clear cell sarcoma [CCS])\r\n* Osteosarcoma\r\n* Wilms tumor \r\n* Rare tumors \r\n** Medullary thyroid carcinoma (MTC)\r\n** Renal cell carcinoma (RCC)\r\n** Hepatocellular carcinoma (HCC)\r\n** Hepatoblastoma \r\n** Adrenocortical carcinoma\r\n** Pediatric solid tumors (including central nervous system [CNS] tumors) with known molecular alterations in the targets of XL184 (i.e., MET amplification, overexpression, activating mutation, MET translocation, MET exon skipping mutations, activating RET mutations, RET rearrangement, overexpression or activation of AXL); documentation of the alteration from a Clinical Laboratory Improvement Act (CLIA) certified laboratory will be required
Subjects with soft tissue sarcoma must have radiographic evidence of progression within the previous 3-4 months and must have received, or been intolerant to, prior treatment with an anthracycline +/- olaratumab or ifosfamide;
Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at time of relapse\r\n* Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)\r\n* Osteosarcoma\r\n* Rhabdomyosarcoma\r\n* Non-rhabdomyosarcoma soft tissue sarcoma \r\n* Desmoplastic small round cell tumor\r\nNote: Patients with known involvement of the central nervous system (CNS) by malignancy will be included if there is no evidence of active bleeding or intratumoral hemorrhage on radiographic imaging
Have histologically or cytologically confirmed Kaposi's sarcoma or gastrointestinal stromal tumor (GIST).
Soft tissue sarcoma subtypes except GIST, desmoid tumors and pleomorphic rhabdomyosarcoma
Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
For Part B dose confirmation: All participants must have histological evidence of advanced or metastatic colon cancer or soft tissue sarcoma. Colon cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
Sarcoma
Diagnosis of Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Wilms tumor or other primary renal tumor (including clear cell and rhabdoid)
Patients with the following pure histologies of endometrial or ovarian cancer are not eligible for enrollment: germ cell, sex cord stroma, carcinosarcoma, or sarcoma.
Presence of measurable disease as defined by the RECIST version 1.1 Cohort 2: Patient Population: Relapsed/Refractory Soft Tissue Sarcoma or Non-Kit GIST
Histologically confirmed diagnosis of advanced, unresectable, or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy excluding: chondrosarcoma, neuroblastoma, osteosarcoma, embryonal rhabdomyosarcoma, or Kaposi sarcoma.
For patients with histiocytic sarcoma, interdigitating dendritic cell sarcoma, or follicular dendritic cell sarcoma only: disease that is not amenable to surgical resection and/or radiation therapy with curative intent
For histological specific cohorts, patients must have confirmed metastatic and/or locally advanced osteosarcoma, chondrosarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma/high grade myxofibrosarcoma, vascular sarcoma, alveolar soft part sarcoma (ASPS), small blue round cell, or leiomyosarcoma (LMS) by the enrolling institution.
Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse - a) Rhabdomyosarcoma, b) Non-rhabdomyosarcomatous Soft Tissue Sarcoma (including desmoplastic small round cell tumor), c) Ewing Sarcoma / Peripheral Primitive Neuroectodermal Tumor (PNET), d) Osteosarcoma, e) Neuroblastoma (Measurable), f) Neuroblastoma (Evaluable), g) Hepatoblastoma.
Stage 1: Histologically confirmed well-differentiated or de-differentiated liposarcoma; if stage 1 of the Simon II stage design fails to meet its endpoint for liposarcoma patients, an additional 16 patients will be enrolled, composed of 4 each of malignant peripheral nerve sheath tumor (MPNST), synovial sarcoma, alveolar rhabdomyosarcoma and alveolar soft part sarcoma (otherwise, an additional 16 patients with well-differentiated or de-differentiated liposarcoma would be enrolled); pathology review occurs at the center enrolling the patient on this trial
Only patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E or V600K mutated tumors will be enrolled
Soft-tissue sarcoma [excluding gastrointestinal stromal tumors (GIST)].
Sarcoma
INCLUSION - PROCUREMENT: Diagnosis of refractory or metastatic GD2-positive sarcoma not responsive to standard treatment; (patients with osteosarcoma do not require GD2 testing of their tumor)
INCLUSION - TREATMENT: Diagnosis of refractory or metastatic GD2-positive sarcoma not responsive to standard treatment; (patients with osteosarcoma do not require GD2 testing of their tumors)
V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) or neuroblastoma (N) RAS mutant tumors
Non-epithelial breast malignancies such as sarcoma or lymphoma.
Patients with gastrointestinal stromal tumor (GIST) tumors and Kaposi’s sarcoma are excluded
Patients who are known to be both V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor alpha (PDGRF?) wild type.
Histologically or cytologically confirmed grade 2 or 3 soft tissue sarcoma that is unresectable or metastatic that would be standardly treated with gemcitabine or gemcitabine and docetaxel; prior surgery for primary or metastatic disease after chemotherapy following a response is allowed
The participant is diagnosed with gastrointestinal stromal tumor (GIST) or Kaposi sarcoma.
Malignancy requiring systemic therapy; Note: Kaposi sarcoma limited to the skin is not exclusionary unless requiring systemic chemotherapy
Neuroendocrine carcinoma or sarcoma histology
Have an intermediate- or high-grade soft tissue sarcoma according to French Federation of Cancer Centers (FNCLCC) criteria
Has one of the following sarcoma subtypes where neoadjuvant chemotherapy is established as practice at our institution: extra-skeletal Ewing’s sarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma (pleomorphic rhabdomyosarcoma is allowed, bone sarcomas including osteosarcoma, Ewings sarcoma and chondrosarcoma are not allowed)
Adult subjects with treatment naie primary or locally recurrent dedifferentiated liposarcoma (DDLPS) of the retroperitoneum or undifferentiated pleomorphic sarcoma (UPS) of the trunk or extremity will be eligible for inclusion in this study only if all of the following criteria apply.
Other terms for undifferentiated pleomorphic sarcoma (UPS) may include, but are not limited to: pleomorphic undifferentiated sarcoma, unclassified spindle cell sarcoma, spindle cell sarcoma not otherwise specified, pleomorphic spindle cell sarcoma, pleomorphic fibroblastic sarcoma, undifferentiated high-grade pleomorphic sarcoma, pleomorphic sarcoma with prominent inflammation, pleomorphic sarcoma with giant cells, malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes), fibrosarcoma, and myxofibrosarcoma (at least intermediate grade; located deep to the fascia in muscle).
Prior radiation therapy for sarcoma in the same area.
Are diagnosed with gastrointestinal stromal tumor or Kaposi sarcoma.
Phase 2: Participants must be diagnosed with histologically confirmed rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) or ewing sarcoma (EWS) which is relapsed or refractory having received at least 1 prior therapy, including primary treatment.
Patients with a biopsy-proven adult-type high-risk soft tissue sarcoma (STS) in the trunk (non-retroperitoneal) or extremities. Histologies will include the most common adult-type STS such as undifferentiated pleomorphic sarcoma, liposarcoma, leiomyosarcoma, fibrosarcoma, synovial sarcoma, angiosarcoma, epithelioid sarcoma and malignant peripheral nerve sheath tumor. STS considered high-risk as defined below:\r\n* Tumors greater than or equal to 5 cm, intermediate or high grade according to French Federation of Comprehensive Cancer Centers (FNCLCC) criteria, and a location deep or superficial to fascia\r\n* Intermediate or high-grade tumors that are locally recurrent, metastatic or have had prior inadequate resections \r\n* Intermediate and high grade tumors shall be grade 2 or 3 based on FNCLCC parameters (Trojani et al, 1984; Coindre 2006)\r\n** Tumor differentiation\r\n*** Score 1 (sarcomas closely resembling normal adult mesenchymal tissue)\r\n*** Score 2 (sarcomas for which histological typing is certain)\r\n*** Score 3 (embryonal and undifferentiated sarcomas)\r\n** Mitotic count (HPF – high power field – 0.17 mm squared)\r\n*** Score 1 (0-9 mitoses per 10 HPF)\r\n*** Score 2 (10-19 mitoses per 10 HPF)\r\n*** Score 3 (greater than or equal to 20 mitoses per 10 HPF)\r\n** Tumor necrosis\r\n*** Score 0 (no necrosis)\r\n*** Score 1 (less than 50% tumor necrosis)\r\n*** Score 2 (greater than or equal to 50% tumor necrosis)\r\n** Histological grade\r\n*** Grade 1 – total score 2 or 3\r\n*** Grade 2 – total score 4 or 5\r\n*** Grade 3 – total score 6, 7 or 8
To limit the heterogeneity of the tumor population and reduce the risk of masking any clinical effect of the treatment regimen, multiple categories of STS subtypes will be excluded:\r\n* Patients with primarily bone-based sarcomas that can occur in the soft tissues, such as: \r\n** Extraskeletal Ewing sarcoma\r\n** Extraskeletal osteosarcoma\r\n** Peripheral chordoma\r\n** Extraskeletal myxoid chondrosarcoma\r\n** Mesenchymal chondrosarcoma\r\n* Patients with predominantly low-grade STS, such as:\r\n** Solitary fibrous tumor / hemangiopericytoma\r\n** Well-differentiated liposarcoma\r\n** Dermatofibrosarcoma protuberans\r\n** Kaposi’s sarcoma\r\n* Pediatric-type STS such as rhabdomyosarcoma\r\n* Gastrointestinal stromal tumors (GIST)
Have had a histologic diagnosis of osteosarcoma, Ewing sarcoma, or rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma either at diagnosis or relapse\r\n* Patients must have experienced relapse after front-line therapy, or have had documented disease progression during front-line therapy
Central nervous system (CNS) metastasis, endometrial leiomyosarcoma, or endometrial stromal sarcoma.
Pathologically confirmed diagnosis of intermediate or high-grade soft tissue sarcoma for which single-agent doxorubicin is appropriate therapy, including but not limited to:\r\n* Synovial sarcoma\r\n* Fibrosarcoma\r\n* Undifferentiated sarcoma\r\n* Liposarcoma\r\n* Leiomyosarcoma\r\n* Angiosarcoma\r\n* Malignant peripheral nerve sheath tumor\r\n* Pleomorphic rhabdomyosarcoma\r\n* Myxofibrosarcoma\r\n* Epithelioid sarcoma\r\n* Undifferentiated pleomorphic sarcoma
Histologic diagnosis for which single-agent doxorubicin is NOT appropriate therapy, including but not limited to:\r\n* Alveolar or embryonal rhabdomyosarcoma\r\n* Ewings sarcoma or primitive neuroectodermal tumor (PNET)\r\n* Osteosarcoma\r\n* Gastrointestinal stromal tumor (GIST)
Patients must have a diagnosis of a locally advanced or metastatic sarcoma that is progressing; the following subtypes (considered genomically complex) will be eligible: leiomyosarcoma (well differentiated or poorly differentiated), undifferentiated pleomorphic sarcoma, myxofibrosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, malignant peripheral nerve sheath tumor, angiosarcoma or extraskeletal osteosarcoma; other potentially genomically complex soft tissue sarcoma (STS) subtypes may be included on a case-by-case basis after discussion with the principal investigator
Non-epithelial breast malignancies such as sarcoma/lymphoma
Have metastatic or unresectable sarcoma
Has one of the following sarcoma subtypes where combining anthracyclines with other chemotherapies is established as the standard of care: osteosarcoma, Ewings sarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma
Non-epithelial breast malignancies such as sarcoma or lymphoma
Histologically or cytologically confirmed sarcoma that fall into one of the following categories;  patients with low-grade tumors are eligible if there is definite evidence of metastasis or progression (defined as at least a 10% increase in the cumulative sum of the longest diameters within a 3 month period)\r\n* Adipocytic tumors (well-differentiated/dedifferentiated liposarcoma, myxoid liposarcoma, pleomorphic liposarcoma)\r\n* Vascular tumors (leiomyosarcoma, angiosarcoma)\r\n* Undifferentiated pleomorphic sarcoma\r\n* Synovial sarcoma\r\n* Osteosarcoma\r\n* Other sarcoma histologies
Must have received and have progressed, are refractory or intolerant to standard therapy appropriate for the specific sarcoma subtype, if there is a standard therapy for the subtype (i.e. progressing well-differentiated liposarcoma, clear cell sarcoma etc do not require prior therapy)
Histologically confirmed soft tissue sarcoma of the extremity/trunk
Non epithelial breast malignancies such as sarcoma or lymphoma
Patients must have histologically confirmed Kaposi sarcoma (KS) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI)
Patients who have been previously treated for metastatic melanoma may be included (e.g. prior treatment with v-raf murine sarcoma viral oncogene homolog B [BRAF] inhibitors and/or ipilimumab will be allowed), provided that they have had a three week ‘washout’ prior to signing consent and have not been treated with a PD-1 blocking antibody
Histologically confirmed grade 2 or 3 soft tissue sarcoma that is unresectable or metastatic; surgery for primary or metastatic disease after chemotherapy following a response is allowed; patients with the following tumor types are eligible:\r\n* Undifferentiated pleomorphic sarcoma\r\n* Leiomyosarcoma\r\n* Malignant fibrous histiocytoma\r\n* Liposarcoma (myxoid/round cell, pleomorphic or dedifferentiated)\r\n* Synovial sarcoma\r\n* Myxofibrosarcoma\r\n* Angiosarcoma\r\n* Fibrosarcoma\r\n* Malignant peripheral nerve sheath tumor\r\n* Epithelioid sarcoma\r\n* Unclassified high-grade sarcoma (not otherwise specified)\r\n* Soft tissue sarcoma for which treatment with an anthracycline is appropriate at the approval of the principal investigator (PI)
Patients must have histologically confirmed diagnosis of osteosarcoma or Ewing sarcoma by central review, except if the diagnosis was already confirmed by the RRePS (Réseau de Référence en Pathologie des Sarcomes et des Tissus Mous et des Viscères) network
Age ? 10 year for Liposarcoma, Osteosarcoma, and Ewing sarcoma; Age ? 5 years for Rhabdomyosarcoma cohorts
Patients must have histologically or cytologically confirmed advanced/metastatic liposarcoma, osteogenic sarcoma, Ewing/Ewing-like sarcoma of soft tissue or bone, fusion-positive alveolar rhabdomyosarcoma or embryonal rhabdomyosarcoma/fusion-negative alveolar rhabdomyosarcoma
For Cohort 2 (subjects with relapsed/refractory synovial sarcoma only), the following tests must be available by local laboratory: Morphology consistent with synovial sarcomas, and cytogenetics or fluorescence in situ hybridization (FISH) and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11)
For Cohort 6 (subjects with epithelioid sarcoma undergoing mandatory tumor biopsy):
Morphology and immunophenotypic panel consistent with epithelioid sarcoma (e.g., CD34, EMA, Keratin, and INI1)
Histologically confirmed diagnosis of locally advanced STS that is unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate\r\n* Examples:\r\n** Resectable stage IIB, III, and IV disease that are not suitable for surgically resection alone due to inability to achieve clear margins\r\n** Including metastatic (stage IV) disease for which radiotherapy and surgical resection are indicated\r\n** Except certain histologic subtypes: gastrointestinal stromal tumor (GIST), Desmoid, Ewing sarcoma, Kaposi sarcoma, and bone sarcomas
Certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, and bone sarcomas
Subjects with retroperitoneal and visceral sarcoma
Documentation of Kirsten rat sarcoma viral oncogene homolog (K-Ras) mutational status
Non-epithelial breast malignancies such as sarcoma or lymphoma
COHORT A: Confirmation in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory that one of the patient’s thyroid tumors (primary tumor, recurrent tumor, or metastasis) has an neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) or Kirsten rat sarcoma viral oncogene homolog (KRAS) or Harvey rat sarcoma viral oncogene homolog (HRAS) mutation at G12, G13, or Q61; this group of patients will also be referred to as “RAS MUT”
COHORT B: Confirmation in a CLIA certified laboratory that one of the patient’s thyroid tumors (primary tumor, recurrent tumor, or metastasis) does not have any of the following mutations:\r\n* Mutation at V600 of the v-raf murine sarcoma viral oncogene homolog B (BRAF) gene\r\n* Mutation in NRAS or KRAS or HRAS at G12, G13, or Q61\r\n* These patients will be designated “BRAF/RAS wild type (WT)”
Only patients with mutated rat sarcoma (RAS) (KRAS and NRAS) mutations are eligible to participate (Phase II only)
Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
Has had prior systemic cancer therapy within the past four weeks or v-raf murine sarcoma viral oncogene homolog B (B-RAF) or mitogen-activated protein kinase (MEK) inhibitors within 7 days at the time of the start of the lymphodepletion regimen (Turnstile II)
Patients must have histologically confirmed soft tissue sarcoma with evidence of metastatic or unresectable disease
The following specific histologic subtypes of soft tissue sarcomas will be excluded: gastrointestinal stromal tumor (GIST), Kaposi’s sarcoma, mesothelioma, dermatofibrosarcoma, chordoma, alveolar soft-part sarcoma; also, all bone sarcomas are excluded including Ewing’s sarcoma, osteosarcoma, GIST, low grade chondrosarcoma, and chordoma
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
Non-epithelial malignancies such as sarcoma or lymphoma.
Patients must have undergone/undergo testing for v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status
Colorectal cancer patients with known v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (for the arm combining bevacizumab, temsirolimus and cetuximab)
Histologically confirmed diagnosis of metastatic or unresectable soft tissue sarcoma, excluding gastrointestinal stromal tumors, Kaposi‘s sarcoma, Ewing‘s family of tumors, and embryonal or alveolar rhabdomyosarcoma
Kaposi sarcoma pathologically confirmed by Department of Pathology, Clinical Center, National Institutes of Health
Patients with concurrent Kaposi sarcoma requiring immediate cytotoxic chemotherapy
Subjects with histology other than adenocarcinoma; examples include: neuroendocrine tumors, acinar cell cancer, sarcoma or lymphoma of the pancreas
Participants must have histologically proven primary (or locally recurrent after prior surgery) soft tissue sarcoma of the retroperitoneum; patients in the phase II portion of the trial will be primary soft tissue sarcomas only; extraskeletal chondrosarcoma is allowed; pathology must be reviewed at treating institution or Dana-Farber (DF)/Harvard Cancer Center (HCC) affiliate prior to study entry (for locally recurrent participants, biopsy and pathology review may be from time of original diagnosis); NOTE: for patients with retroperitoneal neoplasms that have ambiguous histological and/or immunohistochemical findings, the diagnoses of carcinoma, melanoma, and lymphoma should be excluded by immunohistochemical studies with antibodies to broad spectrum cytokeratin (AE1/AE3), S-100, cluster of differentiation (CD)45, or LCA (leucocyte common antigen), respectively; if these diagnoses are excluded by immunohistochemistry, then patients presenting with primary non-visceral retroperitoneal masses that are felt to be \consistent with sarcoma\ shall be considered eligible for this trial
No prior radiation therapy for retroperitoneal sarcoma is allowed
Participants with sarcoma of head and neck, lung, heart or extremity origin; or histopathology demonstrating rhabdomyosarcoma, extraosseous primitive neuroectodermal tumor (PNET) soft tissue Ewing's sarcoma, osteosarcoma, Kaposi's sarcoma, angiosarcoma, aggressive fibromatosis (desmoid tumor), or dermatofibrosarcoma protuberans or chondrosarcoma other than extraskeletal chondrosarcoma; or well differentiated liposarcoma where the target volume cannot be adequately distinguished from the normal retroperitoneal fat are excluded
Non-epithelial breast malignancies such as sarcoma or lymphoma
Patients with lobular carcinoma in-situ alone (no invasive component) and patients with non-epithelial breast malignancies such as sarcoma or lymphoma
Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive sarcoma, not treatable by surgical resection
Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive sarcoma, not treatable by surgical resection and with disease progression after receiving at least one prior systemic therapy
Patients must be receiving a v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) inhibitor and failed to achieve PR or CR or have progressive disease in response to B-RAF treatment (Cohort C)
Phase II: patients must have histologically verified tumor at initial diagnosis and radiologically or histologically confirmed status at inclusion as indicated in the following: neuroblastoma, osteosarcoma, rhabdomyosarcoma or Ewing sarcoma.
Diagnosis: Histologically confirmed rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) (Grade 2 or 3), or Ewing sarcoma (EWS) which is relapsed or refractory (failed front line therapy)
Histopathology other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
Part B dose expansion: Must have confirmed Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal cancer that is metastatic or recurrent and has failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant of irinotecan or oxaliplatin
Histologically or cytologically confirmed diagnosis of Ewing sarcoma and have progressed on or after standard therapies.
Histological diagnosis of synovial sarcoma
Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT).
In expansion cohort only: patient’s kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status must be known prior to enrollment
Histopathologic documentation of synovial sarcoma or myxoid liposarcoma with the diagnosis of advanced or recurrent disease.
All sites of disease must be resectable or borderline resectable as assessed by a surgical oncologist with experience in retroperitoneal sarcoma resection after discussion in our institutional multidisciplinary sarcoma tumor board conference
Histologically proven RMS (with fusion status) or undifferentiated sarcoma of the pelvis or abdomen, group 3 (as defined by the IRS, intergroup rhabdomyosarcoma study group staging system seen in addendum 1)
Have mCRC that has been treated with currently approved standard therapies, including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy, and, if Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type, an anti-epidermal growth factor receptor (EGFR) therapy
Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study)
Excluded tumor types\r\n* Melanoma\r\n* Bone sarcomas\r\n* Soft tissue sarcomas, including angiosarcoma, primary cutaneous leiomyosarcoma, dermatofibrosarcoma protuberans\r\n* Leukemias\r\n* Myeloid sarcoma, leukemia cutis, and chloroma\r\n* Hodgkin’s lymphoma\r\n* B cell lymphoma
Unresectable or metastatic melanoma with known v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation status
Patients must have known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status of tumor; wild-type (WT) or mutated, prior to randomization
Newly diagnosed and histopathologically confirmed (by central pathology review) potentially resectable soft tissue sarcomas of the extremity and trunk of the following subtypes: liposarcoma (excluding myxoid liposarcoma), leiomyosarcoma and undifferentiated pleomorphic sarcoma\r\n* An incisional or core biopsy is the preferred method for diagnosis; fine needle aspiration is not acceptable\r\n* Sites permissible for biopsy include\r\n** Extremities: upper (including shoulder) and lower (including hip)\r\n** Trunk: body wall
Patients must have histologically confirmed grade 2 or 3 tumors by the French Federation of Cancer Centers Sarcoma Group (FNCLCC) sarcoma grading system
Patients must have a sarcoma in the extremity or trunk in location, which is accessible to direct or ultrasound guided injections
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
TREATMENT: Patients with melanoma and known v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations must have received and progressed on specific BRAF inhibitor therapy
Patients with history of rat sarcoma (RAS) mutation-positive tumors are not eligible regardless of interval from the current study; Note: RAS testing and absence of RAS mutation are required for eligibility
Prior chemotherapy, including targeted therapy such as v-raf murine sarcoma viral oncogene homolog B1 (BRAF) or mitogen-activated protein kinase kinase (MEK) inhibition
Patient eligibility will be based on a diagnosis of Ewing sarcoma or PNET by institutional pathologist
Patients with pathologic diagnoses other than Ewing sarcoma will be excluded
Patients diagnosed with Ewing Sarcoma as a second malignant neoplasm are not eligible if they have received chemotherapy or radiation for the treatment of their primary malignancy
COHORT EXPANSION PHASE: Histological or cytopathological diagnosis of advanced/metastatic unresectable colorectal cancer with known rat sarcoma viral oncogene homolog (RAS) mutational status; patients with known B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations will not be eligible for the expansion cohort; all patients must have received and progressed or be intolerant of an oxaliplatin-containing regimen and an irinotecan-containing regimen
Diagnosis: \r\n* Phase 1 (Part A)\r\n** Solid tumors (Part A1): patients with relapsed or refractory solid tumors including central nervous system (CNS) tumors without bone marrow involvement are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)\r\n** Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) (Part A2): patients with relapsed or refractory Ewing sarcoma or peripheral PNET without bone marrow involvement will be eligible for Part A2 if there are no available slots on Part A1; these patients will be enrolled at one dose level below the dose level at which patients on Part A1 are actively enrolling, or at the starting dose level (dose level 1) if dose escalation has not yet occurred; patients must have had histologic verification of malignancy at original diagnosis or relapse\r\n* Phase 2 (Part B)\r\n** Ewing sarcoma or peripheral PNET: patients with relapsed or refractory Ewing sarcoma or peripheral PNET are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse\r\n* Phase 2 (Part C)\r\n** Acute lymphoblastic leukemias (ALL): patients must have 2nd or greater relapse of pre-B ALL or T-cell ALL; patients may not have refractory disease\r\n** Patients with ALL must have had histologic verification of the malignancy at the most recent relapse, including immunophenotyping to confirm diagnosis
Patients with history of rat sarcoma (RAS) mutation-positive tumors are not eligible regardless of interval from the current study; Note: prospective RAS testing is not required; however, if the results of previous RAS testing are known, they must be used in assessing eligibility
Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
Tumor may have a v-raf murine sarcoma viral oncogene homolog B (B-RAF) V600 mutation or be BRAF wild type, and patients must not have been previously treated with ipilimumab
Patients with histology consisting of endometrial stromal sarcoma, leiomyosarcoma or malignant mixed Mullerian tumor (MMMT or carcinosarcoma)
Tumor must have a v-raf murine sarcoma viral oncogene homolog B (B-RAF) V600E, D or K mutation by Cobas pyrosequencing assay or equivalent
** Note: Evidence for MET mutation or amplification is defined as:\r\n*** Positive for c-Met amplification by FISH; or\r\n*** Positive for known c-Met kinase domain activating mutations including V1110L, H1112L, H1112Y, H1124D, M1149T, T1191I, V1206L, L1213V, V1238I, M1268T, P1009S, T1010I, R988C, V941L, but excluding Y1248C, Y1248H, Y1248D, and Y1253D; or\r\n*** Chromosomal translocations that lead to altered transcriptional regulation of c-Met and/or hepatocyte growth factor (HGF) including metastatic alveolar soft part sarcoma, clear cell sarcoma, rhabdomyosarcoma, or translocation associated renal cell carcinoma)
Epithelioid sarcoma
Synovial sarcoma with SS18-SSX rearrangement
For subjects with synovial sarcoma only, the following test results must be available: Morphology consistent with synovial sarcoma, and cytogenetics or FISH and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11) For Dose Expansion Only:
Epithelioid sarcoma
Cohort 4 - Tumor types eligible for Cohorts 1 through 3 or synovial sarcoma with SS18-SSX rearrangement
For subjects with synovial sarcoma with SS18-SSX rearrangement (in Cohort 4 only) - have the following test results available:
Morphology consistent with synovial sarcoma, and
Locally advanced, relapsed, or metastatic sarcoma with measurable tumor burden following therapy, as defined by RECIST v1.1; the total of all lesions must be ?12 cm (for synovial sarcoma) or ?15 cm (for myxoid/round cell liposarcoma [MRCL]).
Tumor histology consistent with synovial sarcoma or MRCL.
Tumor histology consistent with one of the following: In Part 1, Dose Escalation - melanoma, NSCLC, ovarian cancer (including fallopian tube carcinoma), or sarcoma (any subtype). In Part 2, Patient Expansion - NSCLC, ovarian cancer (including fallopian tube carcinoma), or the sarcoma subtypes, synovial sarcoma or myxoid/round cell liposarcoma
Histologically confirmed diagnosis of nonresectable or metastatic soft tissue sarcoma; the following histologies are excluded: embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumors, primitive neuroectodermal tumors, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma, and mixed mesodermal tumors of the uterus
Patients may not have received prior MEK, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor therapy
Histologically confirmed Ewing sarcoma
Evidence of Ewing sarcoma translocation by FISH or RT-PCR.
Histologically confirmed unresectable soft tissue sarcoma (i.e., non-GIST, non-adipocytic) that has progressed following treatment with chemotherapy. Prior pazopanib is allowed if the drug was not discontinued for toxicity ( Phase 1 only)
Histologically confirmed metastatic soft tissue sarcoma (i.e., non-GIST, non-adipocytic) that has progressed by RECIST following treatment with anthracycline chemotherapy. Patients may have received up to four lines of systemic therapy for metastatic disease and no more than two lines of combination treatment ( Phase 2 only)
Prior progression following a fluoropyrimidine-based therapy and progression following or intolerance to irinotecan and oxaliplatin, as well as anti-epidermal growth factor receptor (EGFR) therapy (e.g., panitumumab or cetuximab) for rat sarcoma viral oncogene homolog (RAS) wild-type patients
For Part C: All participants must have histological evidence of advanced or metastatic specific subtypes of soft tissue sarcoma.
Have a histologically confirmed diagnosis of STS for which olaratumab and doxorubicin would be appropriate therapy. Participants with a diagnosis of Grade 1 liposarcoma are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. Participants with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Participants must have potentially resectable disease (as assessed by the study investigator) and have a primary tumor lesion deemed amenable to serial biopsy.
Colon cancer other than adenocarcinoma (e.g., sarcoma, lymphoma, carcinoid).
Patients with wild-type or mutant Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC)
have prior or concurrent malignancies, inclusive of hematologic, primary brain tumor, sarcoma, and other solid tumors, unless in complete remission with no therapy for a minimum of 5 years
Diagnosis of melanoma or other non-epithelial based malignancy such as sarcoma, neuroendocrine tumor, small cell lung cancer
A diagnosis of metastatic or unresectable sarcoma
Determined to have detectable mutations in codons 12 or 13 of the kirsten rat sarcoma (KRAS) oncogene by an investigational assay at the study JPBK central laboratory. A KRAS positive mutation result in codons 12 or 13 of the KRAS oncogene from tumor tissue per local laboratory will be permitted in no more than 10% of randomized participants.
In situ lobular carcinoma or non-epithelial breast malignancies such as sarcoma or lymphoma
Patients with documented c-v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutations
Non-epithelial breast malignancies such as sarcoma or lymphoma
Patients must have their tumor sent for v-Raf murine sarcoma viral oncogene homolog B1(BRAF) mutational analysis
Patients with biopsy proven NRSTS or bone sarcoma
Histologically confirmed diagnosis of advanced unresectable or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy. Participants with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Note: Evidence of disease progression is required for participants that are not newly diagnosed.
Diagnosis of GIST or Kaposi sarcoma.
Participants must have pathologically confirmed soft-tissue sarcoma, which is metastatic or unresectable, sarcoma with no curative multimodality options (pathology review required for patients with pathology not previously reviewed at Dana-Farber Cancer Institute [DFCI], Brigham and Women's Hospital [BWH] or Massachusetts General Hospital [MGH])
Previously untreated Ewing sarcoma and rhabdomyosarcoma
Patients must have a histologically confirmed solid tumor malignancy at either original diagnosis or relapse for which no curative therapy exists, and which has either recurred or progressed after at least one prior systemic therapy; patients with primary brain tumors, or those with brain metastases at time of potential enrollment, are excluded; additionally, patients with gastrointestinal stomal tumors (GIST), alveolar soft part sarcoma, or dermatofibrosarcoma protuberans are excluded
Current evidence of GIST, alveolar soft part sarcoma, or dermatofibrosarcoma
Patients with synovial sarcoma confirmed by Memorial Sloan-Kettering Cancer Center (MSKCC) pathological review
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutated colorectal cancer
Histologically confirmed, soft-tissue sarcoma: excluding rhabdomyosarcoma (pleomorphic rhabdomyosarcoma patients are eligible), Ewing’s, primitive neuroectodermal tumor (PNET), osteosarcoma, or gastrointestinal stromal tumor
Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on body wall
Evaluation of v-raf murine sarcoma viral oncogene homolog B (BRAF)V600 mutation status
Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
Patients with any of the following sarcoma histologic subtypes will not be eligible for participation:\r\n* Alveolar soft-part sarcoma\r\n* Chondrosarcoma\r\n* Dermatofibrosarcoma\r\n* Ewing sarcoma\r\n* Gastrointestinal stromal tumor (GIST)\r\n* Kaposi sarcoma (non-human immunodeficiency virus [HIV] and HIV related disease)\r\n* Mixed mesodermal tumor/carcinosarcoma\r\n* Low grade (grade 1) sarcomas\r\n* Rhabdomyosarcoma (embryonal, alveolar)\r\n* Interdigitating dendritic sarcoma\r\n* Giant cell tumor of the bone
Histologically confirmed diagnosis of unresectable, recurrent, and/or metastatic high grade soft-tissue or bone sarcoma of one of the following subtypes: soft tissue sarcomas (leiomyosarcoma, poorly differentiated/de-differentiated liposarcoma, high grade pleomorphic undifferentiated sarcoma/MFH and synovial sarcoma), and bone sarcomas (Ewing sarcoma, osteosarcoma, and chondrosarcoma [de-differentiated or mesenchymal]).
Histologically confirmed diagnosis of metastatic or recurrent uterine cancer (endometrial carcinoma, carcinosarcoma, clear cell carcinoma, leiomyosarcoma, undifferentiated sarcoma, high grade endometrial stromal sarcoma) by Memorial Sloan Kettering Cancer Center; carcinosarcomas, endometrioid and clear cell carcinomas that appears to have arisen in the ovary/fallopian tube are also eligible; recurrence should not be amenable to curative approaches such as surgical resection or chemoradiotherapy
Group A: newly diagnosed patient less than 14 years of age at the time of diagnosis with histologically proven non-pelvic localized Ewing sarcoma family of tumor involving the bone or soft tissue
Participants must have a primary soft tissue sarcoma or isolated local recurrent sarcoma without prior radiation; open incisional biopsy or core biopsy should be performed to establish the diagnosis of soft tissue sarcoma; slides must be reviewed and assigned a histologic diagnosis and grade by an expert sarcoma pathologist
Participants must have histologically intermediate- or high-grade soft tissue sarcoma
Participants must be determined by an expert sarcoma surgeon to have resectable disease located on the upper extremity (including shoulder), lower extremity (including hip), trunk, retroperitoneum, or pelvis
Histologically confirmed solid tumor or lymphoma at original diagnosis:\r\n* Ewing sarcoma family of tumors (ESFT)\r\n* Gastrointestinal tumors\r\n* Germ cell tumors\r\n* Hepatic tumors (including hepatocellular carcinoma and hepatoblastoma)\r\n* Lymphoma (including Hodgkin and non-Hodgkin lymphoma)\r\n* Kidney tumors (including Wilms tumor, rhabdoid tumors, clear cell carcinoma, and renal cell carcinoma)\r\n* Melanoma\r\n* Neuroblastoma\r\n* Soft tissue sarcoma (including rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma)
Histologically or cytologically confirmed diagnosis of sarcoma of soft tissue; (patients with liposarcoma, bone sarcoma or gastrointestinal stromal tumor [GIST] will be excluded)
Patients with sarcoma, renal cell carcinoma, or melanoma or with known disease outside the lungs and/or thorax
Patients without sarcoma, renal cell carcinoma, or melanoma
Patients must have histologically confirmed relapsed/refractory Ewing's sarcoma or neuroblastoma
Subjects with lobular neoplasm, metastatic carcinoma to breast, sarcoma, Phylloides tumor, or Paget's disease
Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on the body wall
Patients with invasive or extensive in-situ lobular carcinoma or non-epithelial breast malignancies such as sarcoma or lymphoma
Well-differentiated liposarcoma or other low grade STS; Kaposi sarcoma, bone sarcomas, cartilage sarcomas and gastrointestinal stromal tumor (GIST)
Planned to receive neoadjuvant or adjuvant chemotherapy for current diagnosis of localized soft tissue sarcoma
For the purpose of the Pediatric study patients with histologic diagnosis of ESFT including: Ewing's sarcoma or primitive neuroectodermal tumor (malignant neuroepithelioma) of the bone or soft tissues, Askin's tumor of the chest and with central nervous system tumors are eligible.
Kaposi's Sarcoma.
Patients must have histologically confirmed alveolar soft part sarcoma; pathology should be confirmed at the Laboratory of Pathology, National Institutes of Health
Patients must have metastatic alveolar soft part sarcoma that is not curable by surgery; patients who have surgically resectable tumors with metastasis will be considered on a case-by-case basis
Kaposi’s sarcoma pathologically confirmed by Center for Cancer Research (CCR) pathology
Group B: Primary sarcoma of bone or soft tissue of the lower extremity.
CRC (Colorectal cancer): Patients with metastatic CRC and known KRAS (Kirsten rat sarcoma viral oncogene homolog) status who are eligible for treatment with regorafenib in accordance with the approved labeling.
Confirmed RAS mutation (neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS] or Kirsten rat sarcoma viral oncogene homolog [KRAS]) or confirmed PTPN11 mutation, measured on peripheral blood or bone marrow aspirate as part of screening prior to study enrollment; mutation status must be confirmed within 45 days of initiation of therapy
Patients with histologically confirmed viral related hepatocellular, SCLC, non-cutaneous/ non-uveal melanoma, ovarian, TNBC, Sarcoma, Bladder and RCC.
SELUMETINIB ARM: Patients must have one of the following as determined by analysis of the primary tumor or a metastatic site in a CLIA certified laboratory:\r\n* Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation or\r\n* Neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutation or\r\n* Harvey rat sarcoma viral oncogene homolog (HRAS) mutation or\r\n* V-raf murine sarcoma viral oncogene homolog B (BRAF) mutation
SELUMETINIB ARM: Any prior exposure to mitogen-activated protein kinase kinase (MEK), rat sarcoma (Ras), or v-raf-1 murine leukemia viral oncogene homolog 1 (Raf) inhibitors
Histopathological documentation of sarcoma
A diagnosis of a metastatic or unresectable sarcoma
Patients must have progressed on or been intolerant of prior oxaliplatin and irinotecan-containing chemotherapeutic regimen and have disease that is not amenable to potentially curative resection; patients who have a known Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type tumor must have progressed or been intolerant to cetuximab or panitumumab-based chemotherapy
Histological documentation of soft tissue sarcoma (biopsy may be historical and may have been obtained from primary tumor or a metastatic site).
Advanced and/or metastatic malignant soft tissue sarcoma of intermediate or high histologic grade. Excluded are the following sarcoma subtypes:
Ewing sarcoma of soft tissue or bone
Alveolar soft part sarcoma
Clear cell sarcoma
Kaposi sarcoma
No prior chemotherapy for current sarcoma, or
Subjects with histologically or cytologically confirmed mCRC, Kirsten rat sarcoma wild-type (KRAS WT) at initial diagnosis
Histological confirmation of intermediate or high grade soft-tissue sarcoma. Tissue must be sent to a central pathology lab for review but will not preclude entry onto the study. Final assignment of tumor grade and histology will be based on the designation provided by the central pathology review.
Current evidence/diagnosis of alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor (GIST), dermatofibrosarcoma (unless transformed to fibrosarcoma), Ewing's sarcoma, Kaposi's sarcoma, mixed mesodermal tumor, clear cell sarcomas.
Patients with pathologically confirmed colon or rectal cancer who have received and progressed or failed following a fluoropyrimidine, irinotecan, and oxaliplatin based chemotherapy regimens will be eligible for this study; patients who have a known Kirsten rat sarcoma viral oncogene homolog (KRAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild type tumor should have progressed or failed following cetuximab or panitumumab based chemotherapy; prior bevacizumab or regorafenib exposure is not mandated on this study as some patients are deemed poor candidates for anti-angiogenesis therapy and never receive these agents
Only patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutated tumors will be enrolled
Patients must have histologically confirmed soft tissue or bone/cartilage sarcoma. Patients with sarcoma of small round blue cell tumor types are allowed. Gastrointestinal stromal tumors (GIST) are excluded.
Tumor must be wild type for the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF oncogenes, and must have known PIK3CA, AKT mutation status and PTEN expression status
Refractory disease defined as: \r\n* Prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-epidermal growth factor receptor (EGFR) therapy if v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wildtype for colorectal adenocarcinoma and\r\n* Prior treatment with fluoropyrimidine and oxaliplatin for small bowel adenocarcinoma
Patient must be refractory to or intolerant of prior therapy with a fluoropyrimidine, oxaliplatin, irinotecan, and/or anti-angiogenic therapy; patients with v-Ki-ras2 Kirsten rat sarcoma (K-RAS) wild type tumors must have received an epidermal growth factor receptor (EGFR) inhibitor such as cetuximab or panitumumab
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.
Patients must have histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable and for which standard treatment that prolongs survival does not exist or is no longer effective
Patients must have histologically confirmed metastatic alveolar soft part sarcoma that is not curable by surgery; diagnosis of malignancy must be confirmed by the department of pathology at the institution where the patient is enrolled prior to patient enrollment
Histologically confirmed all-rat sarcoma viral oncogene homolog (RAS) wild type; paraffin-embedded tumor tissue obtained from the primary tumor or metastasis
Melanoma must be documented to contain a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation by a Clinical Laboratory Improvement Amendments (CLIA) approved assay
Patients with colorectal carcinoma with tumors that demonstrate a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation
Histologically confirmed diagnosis of soft tissue sarcoma of high or intermediate grade with one of the following histological subtypes:
Adipocytic sarcoma, including:
Subjects should have received at least two standard systematic regimens for advanced soft tissue sarcoma one of which must have included an anthracycline (unless contraindicated).
Due to availability of effective first- and second-line therapies (as well as disease-specific clinical trials), patients with diagnosis of active Kaposi sarcoma will be excluded from study participation; however, persons with other active malignancy with prior history of Kaposi sarcoma can be considered for participation at the discretion of the Study Chair
Diagnosis:\r\n* Rhabdomyosarcoma: embryonal or alveolar\r\n* Ewing’s sarcoma family of tumors (ESFT), which include: classical, atypical, and extraosseous ESFT, peripheral primitive neuroectodermal tumors, peripheral neuroepithelioma, primitive sarcoma of bone, and ectomesenchymoma\r\n* Neuroblastoma: may be diagnosed via histology or the standard clinical evidence for increased catecholamines in the urine plus tumor cells in the bone marrow\r\n* Undifferentiated or embryonal sarcoma\r\n* Desmoplastic small round cell tumor\r\n* Synovial cell sarcoma
Diagnosis of Ewing sarcoma (ES), which includes: classical, atypical, and extraosseous ES, peripheral primitive neuroectodermal tumors, peripheral neuroepithelioma
Diagnosis: \r\n* Part A: Recurrent or refractory neuroblastoma or melanoma\r\n* Part B: Recurrent or refractory neuroblastoma or melanoma\r\n* Part C: Recurrent or refractory osteosarcoma and Ewing sarcoma
Known or suspected current diagnosis of underlying malignancy including high grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma
Ewing’s sarcoma\r\n * Ewing's sarcoma, or other primitive neuroectodermal tumor (PNET) patients will be eligible if relapse occurs following an autologous transplant or if the patient relapses following initial treatment, but is not eligible for an autologous transplant; patients who do not achieve a complete response (CR) with initial therapy will also be eligible, provided they can be rendered free of bulky disease as defined above\r\n * Patients with Ewing’s sarcoma who present with bone or bone marrow metastasis will be eligible in first CR or partial response (PR)
Wilm's tumor and clear cell sarcoma\r\n * Patients with Wilm’s tumor or clear cell sarcoma will be eligible if relapse occurs following an autologous transplant or if the patient relapses following initial treatment, but is not eligible for an autologous transplant; patients who do not achieve a CR with initial therapy will also be eligible provided they can be rendered free of bulky disease as defined above
Osteogenic sarcoma\r\n * Patients with osteogenic sarcoma will be eligible if they do not achieve a CR following initial therapy \r\n * Patients who relapse with pulmonary or bone metastases and do not achieve a CR with surgery and/or chemotherapy will also be eligible
Histologically undifferentiated carcinomas or collecting duct carcinoma, lymphoma, sarcoma or subjects with metastatic renal sites.
RAS wild-type status (by a Clinical Laboratory Improvement Amendments [CLIA] certified assay that includes all known mutations in Kirsten rat sarcoma viral oncogene homolog [KRAS], Harvey rat sarcoma viral oncogene homolog [HRAS], and neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS])
Medical history including histopathological documentation of sarcoma
A diagnosis of synovial sarcoma or myxoid/round cell liposarcoma
If there is a patient with an NY-ESO-1 expressing soft tissue sarcoma who would be otherwise eligible for the trial, which is either not synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCL) or there is controversy about the diagnosis, eligibility will be decided by the PI
Lower extremity or pelvic soft tissue sarcoma necessitating radiation prior to surgical resection
Recurrent soft tissue sarcoma
(Part 1 only) Have a histologically/cytologically confirmed diagnosis of advanced solid tumor, including sarcoma that is refractory to standard therapy. (Part 2 only) Have a histologically confirmed diagnosis of advanced, unresectable, or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy.
(Part 2 only) Current evidence/diagnosis of alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor, dermatofibrosarcoma (unless transformed to fibrosarcoma), Ewing's sarcoma, Kaposi's sarcoma, mixed mesodermal tumor, or clear cell sarcomas.
Sarcoma clinic patient
Diagnosis of soft tissue sarcoma that has been histologically confirmed by an approved reference pathologist
Sarcoma of lower extremity location
Sarcoma location other than lower extremity
Patients must have a new diagnosis of osteosarcoma or Ewing’s sarcoma of bone
Biopsy proven sarcoma located in the extremities
Patient to be treated with radiation therapy for a primary extremity soft tissue sarcoma or recurrent tumor after surgery, followed by surgical resection
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
Parent- or self-reported (for participants 18+ years old) physician diagnosis of sarcoma
PROVIDERS: At least 5 years' experience treating adolescents with sarcoma
Patient in the Sarcoma, Solid Tumor Gastrointestinal (ST GI), or Thoracic Medicine service at Memorial Sloan Kettering Cancer Center (MSK)
Diagnosed with invasive malignancy including: breast, gastrointestinal track, female or male genitourinary system, sarcoma of bone or soft-tissue, leukemia and lymphoma
Patient is newly diagnosed with LE malignancy as shown by biopsy.; diagnoses include: osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath sarcoma, malignant fibrous histiocytoma of the bone and chondrosarcoma of the bone, or any other LE malignancy that requires surgical intervention
Prior AML therapy, with the exception of intrathecal chemotherapy or emergent radiation for myeloid sarcoma.
Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (any G12, G13, Q61) confirmed by Clinical Laboratory Improvement Act (CLIA)-certified testing
Participant must have histologically confirmed Ewing’s sarcoma
The Ewing’s sarcoma must have progressed following at least one standard prior chemotherapy regimen
Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
Suspected malignancy scheduled to be treated with surgical resection at the sarcoma or cancer center of participating sites
Suspected or confirmed diagnosis of a bone sarcoma or osteomyelitis
This study will include only patients with sarcoma, prostate, breast, brain or metastatic cancer; in the future other patient groups may be included through amendment of this protocol
All St Jude patients with a known or suspected, newly diagnosed bone or soft-tissue sarcoma who will be treated on or as per disease specific protocols
Patients with tumors other than neuroblastoma must meet both the following criteria:\r\n* Have one of the following diagnoses (these tumors are known to express GD2 on cell surface):\r\n** Melanoma\r\n** Osteogenic sarcoma\r\n** Leiomyosarcoma\r\n** Ewing sarcoma\r\n** Liposarcoma\r\n** Fibrosarcoma\r\n** Malignant fibrous histiocytoma\r\n** Spindle cell sarcoma\r\n** Small cell lung cancer\r\n** Medulloblastoma metastatic to extracranial sites\r\n** Paraganglioma\r\n* Have refractory or relapsed or metastatic disease
Must have a biopsy-proven high-grade retroperitoneal or soft tissue extremity sarcoma confirmed by independent evaluation of a University of North Carolina (UNC) sarcoma specialized pathologist
Biopsy proven Kaposi’s sarcoma involving the skin or mucosa
Patients must have a current diagnosis of sarcoma, lymphoma, or HER2(-) breast cancer
Patients with biopsy and/or conventional imaging (CT/MRI) proven STS or bone sarcoma with a measurable soft tissue component; these include patients with extremity, retroperitoneal, chest wall, or head and neck primary sarcomas
Low-grade sarcomas as well as alveolar soft parts sarcoma, clear cell sarcoma, extraskeletal myxoid chondrosarcoma, well-differentiated liposarcoma, gastrointestinal stromal tumor, chordoma
-  15 years of age or older\n\n          -  Patients with metastatic sarcoma who have had no more than one prior systemic\n             treatment for metastatic disease\n\n          -  Patients with recurrent sarcoma at relapse\n\n          -  Patients with confirmed histological diagnosis of sarcoma or suspected diagnosis of\n             sarcoma. Some specific subtypes of sarcoma are NOT eligible (Gastrointestinal Stromal\n             Tumor (GIST), carcinosarcoma, sarcomatoid mesothelioma, and metastatic phyllodes\n             tumor)\n\n          -  If initial suspected diagnosis of sarcoma, must have sarcoma diagnosis confirmed prior\n             to proceeding with PDX drug sensitivity testing\n\n          -  Must have measureable disease for computed tomography (CT) scan or magnetic resonance\n             imaging (MRI) evaluation following biopsy or surgery to obtain tissue for PDX\n             development.\n\n          -  No plan for concurrent chemoradiation, for target lesions that will be used for drug\n             treatment correlation with PDX\n\n          -  Fresh tumor tissue available for PDX development\n\n          -  Eastern Cooperative Oncology Group performance status of 0-1\n\n          -  Life expectancy exceeds 6 months\n\n          -  Plan to receive systemic therapy\n\n          -  Informed consent
Subjects must have histologically proven osteogenic sarcoma, malignant fibrous histiocytoma (MFH), or Ewing sarcoma
A tumor that is known to have a v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutation
A diagnosis of synovial sarcoma and myxoid/round cell liposarcoma
Diagnosed with advanced (metastatic or unresectable) sarcoma
Prior treatment with MEK or v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors
Have a Stage IV diagnosis of 1 of the following: Part A: NSCLC (Kirsten rat sarcoma mutant [KRAS mt], PD-L1+); Part B: NSCLC (squamous histology); or Part C: metastatic breast cancer (HR+, HER2-).
Histologically or cytologically confirmed diagnosis of Ewing sarcoma (including ESFT) in subjects with relapsed or refractory disease who have failed standard therapy