Sunitinib in Treating Patients With Metastatic, Locally Advanced, or Locally Recurrent Sarcomas

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed connective tissue neoplasm, including any of the following neoplastic subtypes:

  • Vascular connective tissue neoplasms
  • Leiomyosarcoma
  • Dermatofibrosarcoma protuberans
  • Chordoma
  • Desmoid tumors
  • High-grade undifferentiated pleomorphic sarcoma (e.g., malignant fibrous histiocytoma [including myxofibrosarcoma])
  • Carcinosarcomas (e.g., malignant mixed Müllerian tumors)
  • Giant hemangiomata
  • Kaposi sarcoma
• Metastatic, locally advanced, or locally recurrent disease

• Measurable disease

  • Tumor lesions in a previously irradiated area may be considered measurable provided there is evidence of growth that cannot be attributed to necrosis or bleeding
• No gastrointestinal stromal tumor sarcomas

• Prior standard neoadjuvant or adjuvant systemic therapy required for patients with the following diagnoses:

  • Rhabdomyosarcoma
  • Osteosarcoma
  • Ewing sarcoma
• No untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as documented on screening CT scan or MRI

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• PT and INR ≤ 1.5
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 1.5 mg/dL
• Calcium ≤ 12 mg/dL
• Blood glucose < 150 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study therapy
• Other malignancies allowed provided sarcoma is the primary disease requiring systemic therapy
• Able to swallow oral medications

• No other disease or illness within the past 6 months, including any of the following:

  • Myocardial infarction
  • Severe or unstable angina
  • Coronary or peripheral artery bypass graft
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Pulmonary embolism
• No evidence of a bleeding diathesis
• No ongoing cardiac dysrhythmias > grade 2
• No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy
• Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan
• No psychiatric illness or social situation that would preclude study compliance
• No pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication
• No prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline EKG
• No hemorrhage ≥ grade 3 in the past 4 weeks

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• No prior sunitinib malate

• No more than 3 prior cytotoxic chemotherapy regimens for metastatic disease

  • Adjuvant chemotherapy for sarcoma completed > 1 year prior to study entry is not considered a line of prior treatment
• At least 2 weeks since prior cytotoxic chemotherapy
• At least 6 weeks since prior carmustine or mitomycin C
• At least 1 week since prior biological therapy or small molecule kinase inhibitors

• At least 3 weeks since prior radiotherapy (except for palliative radiotherapy to specific sites)

  • Prior palliative radiotherapy allowed provided it is considered medically necessary and there are other target lesions to assess
• More than 4 weeks since prior major surgery
• Concurrent major surgery allowed provided study drug is stopped 2 weeks before surgery and resumed 2 weeks after surgery
• Concurrent palliative radiotherapy (e.g., focal radiotherapy to a bony metastasis for relieving bone pain) allowed
• No other concurrent investigational drugs
• No concurrent participation in another clinical trial

• No concurrent therapeutic anticoagulation (e.g., warfarin)

  • Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided requirements for PT and INR are met

• No other concurrent approved or investigational anticancer agents or treatment, including chemotherapy, biological response modifier therapy, hormonal therapy, or immunotherapy

  • Concurrent hormone replacement therapy for adrenal insufficiency allowed
• No concurrent antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent rifampin, theophylline, ketoconazole, or Hypericum perforatum (St. John's wort)