Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

Inclusion Criteria:

• Note: eligible patients must have a body surface area >= 0.5 m^2 AND be able toswallow whole tablets

• Newly diagnosed and histopathologically confirmed, potentially resectable NRSTS ofthe extremity and trunk will be eligible for the chemotherapy or non-chemotherapycohort based on:

• Evidence of chemotherapy sensitivity of the histologic sarcoma subtype based onexisting evidence from prior clinical trials

• Sufficient risk of metastatic disease to warrant chemotherapy based on size andgrade and

• Medically deemed able or unable to undergo chemotherapy

• Notes: an incisional biopsy or core biopsy is preferred; fine needle aspirationbiopsy is not acceptable to establish the diagnosis

• ELIGIBLE SITES:

• Extremities: upper (including shoulder) and lower (including hip)

• Trunk: body wall

• INELIGIBLE SITES: Head and neck, visceral organs (with the exception of embryonalsarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines ofthe bony pelvis

• ELIGIBILITY FOR CHEMOTHERAPY COHORT:

• Stage T2a/b (> 5 cm) and grade 2 or 3 AND

• One of the following chemosensitive histologies as defined in the World HealthOrganization (WHO) classification of soft tissue tumors (with some evidence of goodresponse to chemoradiation and of sufficient high risk of metastases, or clearevidence of metastases):

• Unclassified soft tissue sarcomas that are too undifferentiated to be placed ina specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma not otherwisespecified [NOS]")

• Synovial sarcoma

• Angiosarcoma of soft tissue

• Adult fibrosarcoma

• Mesenchymal (extraskeletal) chondrosarcoma

• Leiomyosarcoma

• Liposarcoma (excluding myxoid liposarcoma)

• Undifferentiated pleomorphic sarcoma

• Embryonal sarcoma of the liver

• Patients meeting the above criteria (histology, size, and grade) with the EXCEPTIONof histologies noted above may enroll on the chemotherapy cohort or thenon-chemotherapy cohort at the discretion of the enrolling investigator; patientsmeeting these criteria with the EXCEPTION of histologies noted above but medicallydeemed unable to receive chemotherapy or who elect not to receive chemotherapy areeligible for the non-chemotherapy cohort

• Patients with the following histologies are only eligible for the chemotherapycohort and cannot enroll on the non-chemotherapy cohort:

• Unclassified soft tissue sarcomas that are too undifferentiated to be placed ina specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma NOS") inpatients < 30 years of age

• Synovial sarcoma

• Embryonal sarcoma of the liver

• ELIGIBILITY FOR NON-CHEMOTHERAPY COHORT:

• Patients with any size of grade 2 or 3 of the following "intermediate (rarelymetastasizing)" or "malignant" tumors, as defined in the WHO classification of softtissue tumors for which we have consensus data of chemotherapy-resistance areeligible only for the non-chemotherapy cohort:

• So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giantcell tumor of soft tissues

• Fibroblastic/myofibroblastic tumors - solitary fibrous tumor, malignantsolitary fibrous tumor, inflammatory myofibroblastic tumor, low grademyofibroblastic sarcoma, myxoinflammatory fibroblastic sarcoma, atypicalmyxoinflammatory fibroblastic tumor, myxofibrosarcoma, low grade fibromyxoidsarcoma, sclerosing epithelioid fibrosarcoma

• Tumors of uncertain differentiation - epithelioid sarcoma, alveolar soft partsarcoma, clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma,ossifying fibromyxoid tumor, myoepithelioma, myoepithelial carcinoma,extraskeletal myxoid chondrosarcoma, neoplasms with perivascular epithelioidcell differentiation (PEComa), intimal sarcoma, atypical fibroxanthoma, mixedtumor NOS, phosphaturic mesenchymal tumor, malignant ossifying fibromyxoidtumor, malignant mixed tumor, malignant phosphaturic mesenchymal tumor

• Chondro-osseous tumors - extraskeletal osteosarcoma

• Pericytic (perivascular) tumors - malignant glomus tumor

• Nerve sheath tumors - malignant peripheral nerve sheath tumor, malignantgranular cell tumor, epithelioid malignant peripheral nerve sheath tumor,malignant Triton tumor

• Undifferentiated sarcomas (with a specific pathologic category in the WHOclassification) - undifferentiated round cell sarcoma, undifferentiatedepithelioid sarcoma, undifferentiated spindle cell sarcoma

• Patients meeting the criteria (histology, size, and grade) with the EXCEPTION ofhistologies noted above may enroll on the non-chemotherapy cohort at the discretionof the enrolling investigator; patients meeting these criteria with the EXCEPTION ofhistologies noted above but medically deemed unable to receive chemotherapy or whoelect not to receive chemotherapy are eligible for the non-chemotherapy cohort; notethat tumors arising in bone are NOT eligible for this study

• Extent of disease:

• Patients with non-metastatic and metastatic disease are eligible

• Initially unresectable patients, with or without metastatic disease, areeligible as long as there is a commitment at enrollment to resect the primarytumor

• Sufficient tissue and blood must be available to submit for required biology studies

• Lansky performance status score >= 70 for patients =< 16 years of age

• Karnofsky performance status score >= 70 for patients > 16 years of age

• Absolute neutrophil count >= 1500/uL; Note: no transfusions are permitted 7 daysprior to laboratory studies to determine eligibility

• Platelet count >= 100,000/uL; Note: no transfusions are permitted 7 days prior tolaboratory studies to determine eligibility

• Hemoglobin >= 8 g/dL for patients =< 16 years of age; >= 9 g/dL for patients > 16years of age; Note: no transfusions are permitted 7 days prior to laboratory studiesto determine eligibility

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or normal serum creatinine based on age/gender as follows:

• 2 to < 6 years; 0.8 mg/dL male; 0.8 mg/dL female

• 6 to < 10 years; 1 mg/dL male; 1 mg/dL female

• 10 to < 13 years; 1.2 mg/dL male; 1.2 mg/dL female

• 13 to < 16 years; 1.5 mg/dL male; 1.4 mg/dL female

• >= 16 years; 1.5 mg/dL male; 1.4 mg/dL female

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) orserum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5x upper limit of normal (ULN) for age

• Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% byradionuclide angiogram

• Corrected QT interval (QTc) < 480 msec

• No evidence of dyspnea at rest, no exercise intolerance, and a resting pulseoximetry reading > 94% on room air if there is clinical indication for determination

• Patients on low molecular weight heparin or Coumadin (with a stable internationalnormalized ratio [INR]) are eligible

• Patient must have a life expectancy of at least 3 months with appropriate therapy

• All patients and/or their parents or legal guardians must sign a written informedconsent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with grade 1 NRSTS tumors of any size are not eligible

• Patients with known central nervous system (CNS) metastases are not eligible; Note:brain imaging is not an eligibility requirement

• Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: patients aged > 17 years with excess of 2.5 mL of hemoptysis are noteligible)

• Patients with gross total resection of the primary tumor prior to enrollment onARST1321 are NOT eligible; patients who have experienced tumor recurrence after agross total tumor resection are NOT eligible

• Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension isdefined as follows:

• Patients aged =< 17 years: greater than 95th percentile systolic and diastolicblood pressure based on age and height which is not controlled by oneanti-hypertensive medication

• Patients aged > 17 years: systolic blood pressure >= 140 mmHg and/or diastolicblood pressure >= 90 mmHg that is not controlled by one anti-hypertensivemedication

• Prior Therapy:

• Patients must have had no prior anthracycline (e.g., doxorubicin, daunorubicin)or ifosfamide chemotherapy

• Patients must have had no prior use of pazopanib or similar multi-targetedtyrosine kinase inhibitors (TKI)

• Patients must have had no prior radiotherapy to tumor-involved sites

• Note: patients previously treated for a non-NRSTS cancer are eligible providedthey meet the prior therapy requirements; patients who have had chemotherapy orradiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior toentering the study or those who have not recovered from adverse events due toagents administered more than 4 weeks earlier are excluded

• Other types of invasive malignancy that are not disease free within 3 years exceptfor non-melanoma skin cancer, lentigo maligna, any carcinoma-in-situ or prostatecancer with low risk factors

• CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patientschronically receiving medications known to be metabolized by CYP3A4 and with narrowtherapeutic indices within 7 days prior to study enrollment, including but notlimited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are noteligible; Note: the use of fentanyl is permitted

• CYP3A4 Inhibitors: patients chronically receiving drugs that are known potent CYP3A4inhibitors within 7 days prior to study enrollment, including but not limited toitraconazole, clarithromycin, erythromycin many non-nucleoside reverse-transcriptaseinhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible

• CYP3A4 Inducers: patients chronically receiving drugs that are known potent CYP3A4inducers within 14 days prior to study enrollment, including but not limited tocarbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are noteligible (with the exception of glucocorticoids)

• Certain medications that are associated with a risk for QTc prolongation and/orTorsades de Pointes, although not prohibited, should be avoided or replaced withmedications that do not carry these risks, if possible

• Subjects with any condition that may impair the ability to swallow or absorb oralmedications/investigational product including:

• Any lesion, whether induced by tumor, radiation or other conditions, whichmakes it difficult to swallow capsules or pills

• Prior surgical procedures affecting absorption including, but not limited tomajor resection of stomach or small bowel

• Active peptic ulcer disease

• Malabsorption syndrome

• Subjects with any condition that may increase the risk of gastrointestinal bleedingor gastrointestinal perforation, including:

• Active peptic ulcer disease

• Known intraluminal metastatic lesions

• Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or othergastrointestinal conditions which increase the risk of perforation

• History of abdominal fistula, gastrointestinal perforation or intra-abdominalabscess within 28 days prior to beginning study treatment

• Subjects with any of the following cardiovascular conditions within the past 6months

• Cerebrovascular accident (CVA) or transient ischemic attack (TIA)

• Cardiac arrhythmia

• Admission for unstable angina

• Cardiac angioplasty or stenting

• Coronary artery bypass graft surgery

• Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which hasbeen treated with therapeutic anticoagulation for less than 6 weeks

• Arterial thrombosis

• Symptomatic peripheral vascular disease

• Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of classII heart failure and is asymptomatic on treatment may be considered eligible

• History of serious or non-healing wound, ulcer, or bone fracture

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements

• Patients who are unable to swallow whole tablets are not eligible

• Patients with a body surface area < 0.5 m^2 are not eligible

• Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviraltherapy are ineligible because of the potential for pharmacokinetic interactionswith pazopanib; in addition, these subjects are at increased risk of lethalinfections when treated with marrow-suppressive therapy

• Patients who are receiving any other investigational agent(s)

• Pregnancy and breast feeding:

• Female patients who are pregnant are ineligible due to risks of fetal andteratogenic adverse events as seen in animal/human studies

• Lactating females are not eligible unless they have agreed not to breastfeedtheir infants during treatment and for a period of 1 month following completionof treatment

• Female patients of childbearing potential are not eligible unless a negativepregnancy test result has been obtained

• Unwillingness to use an effective contraceptive method for the duration of theirstudy participation and for at least 1 month after treatment is completed ifsexually active with reproductive potential