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

Inclusion Criteria

• •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)