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

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib works 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.

Eligibility 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)