Sunitinib Malate in Treating Patients With Persistent or Recurrent Clear Cell Ovarian Cancer

Inclusion Criteria:

• Diagnosis of recurrent or persistent clear cell ovarian cancer, meeting 1 of the following criteria:

  • Primary tumor with ≥ 50% clear cell histomorphology
  • Histologically confirmed recurrence with ≥ 50% clear cell histomorphology

• Tumors must be negative for expression of WT-1 antigen and estrogen receptor antigen by IHC

  • If the primary tumor had ≥ 50% clear cell histomorphology, a biopsy of the recurrent or persistent tumor is not required
  • If the primary tumor had < 50% clear cell histomorphology (or if slides of the primary tumor are not available), a biopsy of the recurrent or persistent tumor is required

• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded)

  • Each lesion must be ≥ 10 mm when measured by CT scan, MRI, or calipers by clinical exam OR ≥ 20 mm when measured by chest x-ray
  • Lymph nodes must be ≥ 15 mm in short axis when measured by CT scan or MRI

• Must have ≥ 1 "target lesion" to be used to assess response as defined by RECIST criteria

  • Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days after completion of radiotherapy

• Must have received one prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for management of primary disease

  • Initial treatment may have included intraperitoneal therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment
  • Must have a platinum-free interval of < 12 months, have progressed during platinum-based therapy, or have persistent disease after platinum-based therapy
  • One additional cytotoxic regimen for management of recurrent or persistent disease allowed
• No primary peritoneal or fallopian tube cancer
• No history or evidence of CNS disease, including primary brain tumor or brain metastases, by physical exam
• Not eligible for a higher priority (e.g., Phase III) GOG clinical trial for the same population, if one exists
• GOG performance status (PS) 0-2 (for patients who received one prior regimen) OR GOG PS 0-1 (for patients who received 2 prior regimens)
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2.5 times ULN (or ≤ 5 times ULN for patients with liver metastases)
• Urine protein < 1+ by urine dipstick OR < 1,000 mg by 24-hour urine collection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy
• No active infection requiring antibiotics except uncomplicated urinary tract infection
• No serious non-healing wound, ulcer, or bone fracture
• No significant traumatic injury within the past 28 days
• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
• No seizures not controlled with standard medical therapy
• No cerebrovascular accident (stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6months

• No clinically significant cardiovascular disease, including any of the following:

  • Poorly controlled hypertension (e.g., systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg)
  • Myocardial infarction or unstable angina within the past 6 months
  • NYHA class II-IV congestive heart failure
  • Cardiac arrhythmia requiring medication
  • Peripheral vascular disease ≥ grade II (e.g., ischemic rest pain, minor tissue loss, ulceration, or gangrene) according to NCI CTC criteria
• No QTc prolongation (> 500 msec)
• No clinically significant peripheral artery disease (e.g., claudication within the past 6 months)

• No pre-existing thyroid abnormality for which thyroid function is unable to be maintained in the normal range with medication

  • History of hypothyroidism allowed provided patient is currently euthyroid
• No other invasive malignancies within the past 5 years except nonmelanoma skin cancer
• No circumstance that does not permit completion of study therapy or required follow-up
• No concurrent amifostine
• Prior biologics allowed, with the exception of anti-angiogenic agents that target VEGF or PDGF
• No prior non-cytotoxic therapy (e.g., VEGF inhibitors, including bevacizumab) for management of recurrent or persistent disease
• No prior sunitinib malate
• No prior cancer treatment that would contraindicate study therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
• At least 3 weeks since any other prior therapy directed at the malignant tumor, including immunologic agents or tamoxifen
• At least 28 days since prior surgery and recovered
• More than 7 days since prior placement of vascular access device or core biopsy
• At least 7 days since prior and no concurrent potent CYP3A4 inhibitors
• At least 12 days since prior and no concurrent potent CYP3A4 inducers

• No concurrent therapeutic doses of Coumadin-derivative anticoagulants (e.g., warfarin)

  • Warfarin administered at doses of ≤ 2 mg daily allowed for prophylaxis of thrombosis
  • Low molecular weight heparin allowed provided PT/INR ≤ 1.5
• No concurrent major surgical procedure