Sunitinib in Treating Patients With Metastatic, Locally Advanced, or Locally Recurrent Sarcomas
Condition: Adult Malignant Fibrous Histiocytoma of Bone; Desmoid Tumor; Endometrial Cancer; Ovarian Cancer; Sarcoma; Small Intestine Cancer
MeSH terms: Sarcoma; Endometrial Neoplasms; Fibromatosis, Aggressive; Intestinal Neoplasms; Histiocytoma; Histiocytoma, Benign Fibrous; Histiocytoma, Malignant Fibrous
Intervention: sunitinib malate
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: chondrosarcoma; recurrent osteosarcoma; localized adult malignant fibrous histiocytoma of bone; metastatic adult malignant fibrous histiocytoma of bone; recurrent adult malignant fibrous histiocytoma of bone; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent Kaposi sarcoma; recurrent uterine sarcoma; adult leiomyosarcoma; adult malignant fibrous histiocytoma; adult rhabdomyosarcoma; dermatofibrosarcoma protuberans; stage III adult soft tissue sarcoma; stage IV adult soft tissue sarcoma; ovarian sarcoma; uterine leiomyosarcoma; stage III uterine sarcoma; stage IV uterine sarcoma; desmoid tumor; adult angiosarcoma; recurrent adult soft tissue sarcoma; uterine carcinosarcoma; endometrial stromal sarcoma; fibrosarcomatous osteosarcoma; chondrosarcomatous osteosarcoma; adult alveolar soft-part sarcoma; adult epithelioid sarcoma; adult extraskeletal chondrosarcoma; adult extraskeletal osteosarcoma; adult fibrosarcoma; adult malignant hemangiopericytoma; adult malignant mesenchymoma; adult neurofibrosarcoma; adult synovial sarcoma; adult desmoplastic small round cell tumor; adult liposarcoma; anaplastic osteosarcoma; mixed osteosarcoma; small intestine leiomyosarcoma; osteoblastic osteosarcoma; telangiectatic osteosarcoma; classic Kaposi sarcoma; immunosuppressive treatment related Kaposi sarcoma; AIDS-related Kaposi sarcoma

Summary:

      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.
    

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)