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

• Patients must have recurrent or persistent clear cell ovarian cancer; primary tumors must be at least 50% clear cell histomorphology in order to be eligible or have a histologically documented recurrence with at least 50% clear cell histomorphology; in addition, the tumors should be negative for expression of Wilms tumor (WT)-1 antigen and estrogen receptor (ER) antigen by immunohistochemistry; appropriate tissue sections must be available for histologic evaluation for central pathology review by Gynecologic Oncology Group (GOG); immunohistochemical stained slides for ER and WT-1 antigen must be available for review by GOG

‣ If the primary tumor had at least 50% clear cell histomorphology, a biopsy of the recurrent or persistent tumor is not required; however, immunohistochemical studies of the primary tumor for ER and WT-1 antigens should be performed and the slides submitted to the GOG for review; the percentage of clear cell histomorphology must be documented in the pathology report or in an addendum to the original report; if slides of the primary tumor are not available for review due to disposal of slides by the histology laboratory (typically 10 years after diagnosis), biopsy of recurrent or persistent disease is required

⁃ If the primary tumor had less than 50% clear cell histomorphology (or if slides of the primary tumor are not available for review), a biopsy of the recurrent or persistent tumor is required to confirm at least 50% clear cell histomorphology and lack of immunoreactivity for ER and WT-1 antigens by immunohistochemistry; the percentage of involvement must be documented in the pathology report or in an addendum to the original report

• All patients must have measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \>= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement 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 or MRI

• Patients must have at least one target lesion to be used to assess response on this protocol as defined by RECIST 1.1; 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 at least 90 days following completion of radiation therapy; thus, a confirmed biopsy in an irradiated area at a date longer than 90 days post-completion of radiation can be considered a target lesion to assess progression and response

• Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment

• Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition:

‣ Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa

• Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease) must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy

• Patients may have received prior biologic therapy, but must not have had any prior therapy with agents which inhibit VEGF, vascular endothelial growth factor receptor (VEGFR) or PDGF such as, bevacizumab, sorafenib, sunitinib, pazopanib, brivanib, aflibercept cediranib, BIBF 1120, imatinib, dasatinib

• Any other prior therapy directed at the malignant tumor, including immunologic agents (e.g. tamoxifen) must be discontinued at least three weeks prior to registration

• Patients must not be eligible for a higher priority (e.g.; Phase III), GOG protocol for the same population if one exists

• Patients must be recovered from effects of recent surgery (28 days must elapse between surgery and the start of treatment with sunitinib malate)

• Patents must have \>= 4 weeks since prior chemotherapy or radiation (\>= 6 weeks for nitrosoureas or mitomycin C)

• Sunitinib metabolizes via liver enzyme, specifically the cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) enzyme; therefore, potential drug interaction with the CYP3A4 enzyme can occur; eligible patients who are on the CYP3A4 inducer or inhibitor enzyme should stop 2 weeks prior to study entry if all other eligibility has been confirmed; the principal investigator will review the case and make all effort to switch such agent to other medication

• Patients should be free of active infection (with the exception of uncomplicated urinary tract infections \[UTI\]) requiring antibiotics

• Patients who have received one prior regimen must have a GOG performance status of 0, 1 or 2; patients who have received two prior regimens must have GOG performance status of 0 or 1

• Absolute neutrophil count (ANC) \>= 1,500/mcl

• Platelets greater than or equal 100,000/mcl

• Creatinine less than or equal to 1.5 times the upper limit of normal (ULN)

• Bilirubin less than or equal to 1.5 ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times the ULN, unless subjects have liver metastasis, in which case both AST and ALT must be less than or equal to 5 times the ULN

• Patients who have met the pre-entry requirements

• Patients must have signed an approved informed consent and authorization permitting release of personal health information