The Efficacy and Safety of Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer

• • Patients must have recurrent or persistent, platinum resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma; platinum-resistant disease is defined as a recurrence within 6 months of completing adjuvant, platinum-based chemotherapy

‣ Patients must have measurable disease or non-measurable (detectable) disease:

• 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 greater than or equal to 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray; lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI

∙ Non-measurable (detectable) disease in a patient is defined in this protocol as one who does not have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria but does have a cancer antigen 125 (CA-125) greater than or equal to two times the upper normal limit within the last 60 days (confirmatory at baseline) and at least one of the following conditions:

‣ Ascites and/or pleural effusion attributed to tumor

⁃ Hypermetabolic lesions on positron emission tomography (PET) scan

⁃ Patients with measurable disease must have at least one target lesion to be used to assess response on this protocol as defined by RECIST

⁃ Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

⁃ Recovery from effects of recent surgery, radiotherapy, or chemotherapy:

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

∙ Any other prior therapy directed at the malignant tumor, including chemotherapy, biological/targeted (non-cytotoxic) agents and immunologic agents, must be discontinued at least three weeks prior to registration

∙ At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy, thoracotomy, video assisted thorascopic surgery (VATS); there is no restriction on minor procedures (e.g., minor: central venous access catheter placement, ureteral stent placement or exchange, paracentesis, thoracentesis)

⁃ Patients must have had one prior taxane and platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organo platinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic (biologic/targeted agents, such as bevacizumab) or extended therapy administered after surgical or non-surgical assessment; there is no maximum number of prior regimens;

⁃ patients may not have had any prior systemic therapy (including interleukin-2, interferon-alpha, chemotherapy, bevacizumab, investigational or licensed drug that targets vascular endothelial growth factor \[VEGF\] or VEGF receptors/pathway or are mammalian target of rapamycin \[mTOR\] inhibitors) for treatment of recurrent ovarian cancer

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

⁃ Patients must meet pre-entry requirements

⁃ A female is eligible to participate if she is of non-childbearing potential or as documentation of a negative pregnancy test prior to the start of the study treatment; sexually active pre-menopausal female subjects must agree to use adequate, highly effective contraceptive measures, while on study and for 45 days after the last dose of last study drug; effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) oral, implantable or injectable contraceptives plus one barrier method; or (c) 2 barrier methods; effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm)