Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Inclusion Criteria:

* • 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)

Exclusion Criteria:

* • Age \< 18 years

  * Patients who have had previous treatment with tivozanib
  * Hemoglobin \< 9.0 g/dL
  * Absolute neutrophil count (ANC) \< 1500 per mm\^3
  * Platelet count \< 100,000 per mm\^3
  * Total bilirubin \> 1.5 × upper limit of normal (ULN) (or \> 2.5 x ULN for subjects with asymptomatic Gilbert's syndrome)
  * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × ULN (or \> 5 × ULN for subjects with liver metastasis)
  * BOTH total bilirubin \> ULN AND AST/ALT \> ULN
  * Alkaline phosphatase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver or bone metastasis)
  * Creatinine \> 2.0 × ULN
  * Prothrombin time (PT) such that international normalized ratio (INR) \> 1.5 x ULN (unless a patient is on therapeutic warfarin) or a partial thromboplastin time (PTT) \> 1.5 x ULN
  * Proteinuria \> 3+ by urinalysis or urine dipstick
  * Significant cardiovascular disease, including:

    * Symptomatic left ventricular dysfunction or baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of =\< lower limit of institutional normal (LLN)
    * Uncontrolled hypertension: systolic blood pressure of \> 140 mmHg or diastolic blood pressure of \> 90 mmHg documented on 2 consecutive measurements taken at least 24 hours apart
    * Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug
    * History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
    * Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
    * Coronary or peripheral artery bypass graft within 6 months of screening
    * History of class III or IV congestive heart failure, as defined by the New York Heart Association
  * Central nervous system metastases; Note: subjects with previously treated (radiotherapy or surgery) brain metastasis that have been stable without steroid treatment for at least 3 months following prior treatment may be enrolled
  * Non-healing wound, bone fracture, or skin ulcer
  * Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
  * Serious/active infection or infection requiring parenteral antibiotics
  * Corrected QT interval (QTc) of \> 480 msec using Bazett's formula
  * Radiotherapy or minor surgical procedure within 2 weeks, or major surgical procedure within 4 weeks prior to administration of first dose of study drug; inadequate recovery from prior surgical procedure
  * Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug, including but not limited to:

    * Deep vein thrombosis
    * Pulmonary embolism
    * Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
    * Peripheral arterial ischemia \> grade 2 (per National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 4.0)
  * Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:

    * Hematemesis, hematochezia, melena or other gastrointestinal bleeding \>= grade 2 (per CTCAE version 4.0)
    * Hemoptysis or other pulmonary bleeding \>= grade 2 (per CTCAE Version 4.0)
    * Hematuria or other genitourinary bleeding \>= grade 2 (per CTCAE Version 4.0)
  * Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; subjects are considered to have a currently active malignancy if they have completed anti-cancer therapy and have not been disease free for \> 2 years
  * Pregnant or lactating females
  * History of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV); subjects on immune suppressive therapy for organ transplant
  * Life-threatening illness or organ system dysfunction compromising safety evaluation
  * Requirement for hemodialysis or peritoneal dialysis
  * Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
  * Known hypersensitivity to drugs chemically related to tivozanib hydrochloride or sunitinib or their excipients
  * Psychiatric disorder or altered mental status precluding informed consent or protocol-related testing