Tivozanib As Maintenance Therapy In GYN
Condition: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma
MeSH terms: Ovarian Neoplasms; Fallopian Tube Neoplasms
Intervention: Tivozanib
Intervention MeSH terms: Tivozanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Platinum-Sensitive; Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; High-grade Serous

Summary:

      This research study is evaluating a drug called tivozanib as a possible treatment for
      ovarian, fallopian tube or primary peritoneal cancer.

      Angiogenesis is the formation of new blood vessels. Tumors need blood vessels to grow and
      spread. Tivozanib is an anti-angiogenesis medicine that fights cancer by cutting off a
      tumor's blood supply so that it does not get the blood and nutrients it needs to grow.

      In this research study, the Investigators are looking to see whether tivozanib works as a
      maintenance therapy for ovarian, fallopian tube or primary peritoneal carcinoma in
      participants who have achieved a complete response following chemotherapy. Maintenance
      therapy is given after a disease has responded to previous treatment. It is given to help
      prevent the spread or recurrence of the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  No evidence of disease on CT/MRI following treatment for recurrent ovarian, fallopian
             tube, or peritoneal cancer.

          -  High-grade papillary serous carcinoma of the ovary, fallopian tube or peritoneum.
             Histological confirmation of the original primary tumor is required.

          -  CA-125 within normal range.

          -  Age greater than or equal to 18 years.

          -  1 prior line of therapy (cytotoxic therapy only) in the recurrent setting is allowed.
             Bevacizumab in the upfront setting allowed, however Bevacizumab or other VEGF pathway
             targeted therapy in the recurrent setting is not allowed. Hormonal therapy does not
             count as a prior line.

          -  Recovered from effects of recent surgery, radiotherapy, and chemotherapy.

          -  ECOG performance status ≤ 2

        Organ and marrow function as defined below:

          -  Absolute neutrophil count ≥1,250/mcL

          -  Platelets ≥100,000/mcL

          -  Bilirubin ≤ 1.5 x ULN

          -  AST (SGOT) / ALT (SGPT) ≤ 2.5 x institutional upper limit of normal Alkaline
             phosphatase ≤ to 2.5 x ULN

          -  Creatinine ≤ 1.5 x institutional upper limit

          -  Less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than 1
             week apart, or < 1 gm protein on 24-hour urine collection or a urine
             protein:creatinine ratio of < 1.

          -  INR < 1.5; if on anticoagulation: INR is required to be between 2 and 3.

        Patient must receive one of these three regimens for their platinum sensitive disease
        (number of cycles should not have exceeded 8 cycles of 1 regimen in the recurrent setting):

          -  Platinum (Carboplatin or Cisplatin) and Taxane (Paclitaxel or Docetaxel) Carboplatin
             and Gemcitabine

          -  Carboplatin and Liposomal Doxorubicin

          -  Females not of childbearing potential or has documentation of a negative pregnancy
             test prior to the start of the study treatment are eligible. 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).

          -  Able and willing to sign a written informed consent document.

        Exclusion Criteria:

          -  Prior therapy with bevacizumab or other VEGF pathway targeted therapy in the recurrent
             setting. Bevacizumab in the upfront setting is allowed.

          -  Receiving any other study agents.

          -  Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin
             or carcinoma in situ of the breast or cervix are eligible. Subjects with prior cancer
             treated with a curative intent with no evidence of recurrent disease 5 years following
             diagnosis and judged by the investigator to be at low risk of recurrence are eligible.
             Subjects with any other concomitant or prior malignancies are ineligible.

          -  Serious non-healing wounds or ulcers at the time of registration.

          -  History of abdominal fistula or gastrointestinal perforation.

          -  Active bleeding.

          -  Clinically significant cardiovascular disease.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Tivozanib.

          -  Symptomatic left ventricular dysfunction or baseline left ventricular ejection
             fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) ≤ 50 %
             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.