A Phase II Evaluation of SU11248 (Sunitinib Malate) (IND #74019, NSC #736511) in the Treatment of Persistent or Recurrent Clear Cell Ovarian Carcinoma

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