Tivozanib As Maintenance Therapy In GYN
Phase: Phase 2
Diagnosis: GYN: Ovarian, Fallopian, Peritoneal Cancer
NCT ID: NCT01972516
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-375
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.
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital
Susana Campos, MD,
Dana-Farber Cancer Institute
Dana-Farber Cancer Institute:
Christin Whalen, 617-582-7738,
- Patients must have no evidence of disease on CT/MRI following treatment for recurrent
ovarian, fallopian tube, or peritoneal cancer. Histological confirmation of the
original primary tumor is required.
- Patient must have high grade papillary serous carcinoma of the ovary, fallopian tube
- Patients must have a CA-125 within normal range.
- Age must be greater than or equal to 18 years of age. Because no dosing or adverse
event data are currently available on the use of Tivozanib in participants <18 years
of age, children are excluded from this study but will be eligible for future
- Patients may have had up to 1 prior line of therapy (cytotoxic therapy only) in the
recurrent setting. Bevacizumab in the upfront setting is 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 (see Appendix A).
- Participants must have normal 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 the 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
- Carboplatin and Liposomal Doxorubicin
- A female is eligible to participate if she is of non-childbearing potential or has
documentation of a negative pregnancy test prior to the start of the study treatment.
Sexually active pre-menopausal female subjects (and male subjects whose sexual
partners are of childbearing potential) 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
- Ability to understand and the willingness to sign a written informed consent
- Participants who exhibit any of the following conditions at screening will not be
eligible for admission into the study.
- Prior therapy with bevacizumab or other VEGF pathway targeted therapy in the
recurrent setting. Bevacizumab in the upfront setting is allowed.
- Participants may not be 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
- 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
- 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
- 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
- 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.