Tivozanib in Recurrent, Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Condition: Recurrent Epithelial Ovarian Cancer; Recurrent Fallopian Tube Cancer; Recurrent Primary Peritoneal Cancer
MeSH terms: Fallopian Tube Neoplasms; Peritoneal Neoplasms; Carcinoma, Ovarian Epithelial; Recurrence
Intervention: Tivozanib
Intervention description: 1.5 mg Given PO (orally)days 1-21 or every 28 day cycle
Intervention MeSH terms: Tyrosine Protein Kinase Inhibitors; Tivozanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: Female
Minimum age: 18 Years
Maximum age: 110 Years
Healthy volunteers: No
Keywords: Cancer; Recurrent; Ovary; Fallopian Tube; Primary Peritioneal; Phase II; Platinum Resistant

Summary:

      This phase II trial studies how well tivozanib works in treating patients with recurrent
      ovarian, fallopian tube, or primary peritoneal cancer. Tivozanib may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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