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

OBJECTIVES:

Primary

• Determine the response rate (complete response and partial response) in patients with metastatic, locally advanced, or locally recurrent non-gastrointestinal stromal tumor sarcomas treated with sunitinib malate.

Secondary

• Determine the 16- and 24-week progression-free survival rate (complete response, partial response, and stable disease) in patients treated with this drug.
• Determine the overall survival in patients treated with this drug.
• Correlate clinical response with changes in soluble angiogenesis mediator levels in patients treated with this drug.
• Determine the tumor maximum standardized uptake values by fludeoxyglucose F 18-PET scan in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified by neoplastic subtype (vascular connective tissue neoplasms, leiomyosarcoma, dermatofibrosarcoma protuberans, chordoma, or desmoid tumors vs high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma (including myxofibrosarcoma)], or other nongastrointestinal connective tissue tumors [including carcinosarcomas]).

Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

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)