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 to
   swallow whole tablets

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

      - Evidence of chemotherapy sensitivity of the histologic sarcoma subtype based on
      existing evidence from prior clinical trials

      - Sufficient risk of metastatic disease to warrant chemotherapy based on size and
      grade and

      - Medically deemed able or unable to undergo chemotherapy

      - Notes: an incisional biopsy or core biopsy is preferred; fine needle aspiration
      biopsy 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 embryonal
   sarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines of the
   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 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):

      - 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]")

      - 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 EXCEPTION of
   histologies noted above may enroll on the chemotherapy cohort or the non-chemotherapy
   cohort at the discretion of the enrolling investigator; patients meeting these
   criteria with the EXCEPTION of histologies noted above but medically deemed unable to
   receive chemotherapy or who elect not to receive chemotherapy are eligible for the
   non-chemotherapy cohort

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

      - 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

      - 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 (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:

      - So-called fibrohistiocytic tumors - plexiform fibrohistiocytic tumor, giant cell
      tumor of soft tissues

      - 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

      - 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

      - Chondro-osseous tumors - extraskeletal osteosarcoma

      - Pericytic (perivascular) tumors - malignant glomus tumor

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

      - Undifferentiated sarcomas (with a specific pathologic category in the WHO
      classification) - undifferentiated round cell sarcoma, undifferentiated
      epithelioid sarcoma, undifferentiated spindle cell sarcoma

   - Patients meeting the criteria (histology, size, and grade) with the EXCEPTION of
   histologies noted above may enroll on the non-chemotherapy cohort at the discretion of
   the enrolling investigator; patients meeting these criteria with the EXCEPTION of
   histologies noted above but medically deemed unable to receive chemotherapy or who
   elect not to receive chemotherapy are eligible for the non-chemotherapy cohort; note
   that 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, are eligible
      as long as there is a commitment at enrollment to resect the primary tumor

   - 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 days prior
   to laboratory studies to determine eligibility

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

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

   - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
   mL/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]) or
   serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
   upper limit of normal (ULN) for age

   - Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by
   radionuclide angiogram

   - Corrected QT interval (QTc) < 480 msec

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

   - Patients on low molecular weight heparin or Coumadin (with a stable international
   normalized 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 informed
   consent

   - 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 not eligible)

   - Patients with gross total resection of the primary tumor prior to enrollment on
   ARST1321 are NOT eligible; patients who have experienced tumor recurrence after a
   gross total tumor resection are NOT eligible

   - Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is
   defined as follows:

      - Patients aged =< 17 years: greater than 95th percentile systolic and diastolic
      blood pressure based on age and height which is not controlled by one
      anti-hypertensive medication

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

   - 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-targeted
      tyrosine 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 provided
      they meet the prior therapy requirements; patients who have had chemotherapy or
      radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to
      entering the study or those who have not recovered from adverse events due to
      agents administered more than 4 weeks earlier are excluded

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

   - CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients
   chronically receiving medications known to be metabolized by CYP3A4 and with narrow
   therapeutic indices within 7 days prior to study enrollment, including but not limited
   to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible;
   Note: the use of fentanyl is permitted

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

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

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

   - Subjects with any condition that may impair the ability to swallow or absorb oral
   medications/investigational product including:

      - Any lesion, whether induced by tumor, radiation or other conditions, which makes
      it difficult to swallow capsules or pills

      - Prior surgical procedures affecting absorption including, but not limited to
      major resection of stomach or small bowel

      - Active peptic ulcer disease

      - Malabsorption syndrome

   - Subjects with any condition that may increase the risk of gastrointestinal bleeding or
   gastrointestinal perforation, including:

      - Active peptic ulcer disease

      - Known intraluminal metastatic lesions

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

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

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

      - 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 has been
      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 class II 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 active
   infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
   arrhythmia, or psychiatric illness/social situations that would limit compliance with
   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 antiretroviral
   therapy are ineligible because of the potential for pharmacokinetic interactions with
   pazopanib; in addition, these subjects are at increased risk of lethal infections 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 and
      teratogenic adverse events as seen in animal/human studies

      - Lactating females are not eligible unless they have agreed not to breastfeed
      their infants during treatment and for a period of 1 month following completion
      of treatment

      - Female patients of childbearing potential are not eligible unless a negative
      pregnancy test result has been obtained

   - Unwillingness to use an effective contraceptive method for the duration of their study
   participation and for at least 1 month after treatment is completed if sexually active
   with reproductive potential