Clinical trial NCT01972516: Tivozanib As Maintenance Therapy In GYN
Official title: A Phase II Study of Tivozanib as Maintenance Therapy, Post-Chemotherapy, in Patients With Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Keywords: Platinum-Sensitive
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
High-grade Serous
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: AVEO Pharmaceuticals, Inc.
First posted: 2013-10-30
Enrollment: 4
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Once the participant has signed the consent form, they will be asked to undergo some screening tests or procedures to find out if the participant can be in the research study. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the participant do not take part in the research study. If the participant has had some of these tests or procedures recently, they may or may not have to be repeated.

* A medical history, which includes questions about the participant's health, current medications, and any allergies.
* Performance status, which evaluates how the participant is able to carry on with their usual activities.
* A tumor assessment by CT (Computerized Tomography) scan or MRI (Magnetic Resonance Imaging.
* Blood tests.
* Urine test.
* Electrocardiogram (ECG)

If these tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.

Additional research procedures to be performed during this study:

- Archival tumor testing: During this study, additional tests will be performed on a sample of the participant's original tumor that has been stored in the institution's tissue banks. These tests will be performed on tumor tissue samples from previous biopsies or surgeries for the participant's cancer.

The research done on these samples will involve looking at DNA and proteins in the participant's cancer to see if researchers can learn more about the participant's type of cancer and understand how tivozanib might work on their tumor. Testing of this sample will not require the participant to undergo any additional research procedures.

This research sample collection is a required part of this research study.

Tissue collection / Ownership: Participation in this protocol involves providing specimen(s) of participant's tissue. Please know that if the investigator leaves the institution, the research and the tissue might remain at the DF/HCC or might be transferred to another institution.

After the screening procedures confirm that the participant are eligible to participate in the research study:

If the participant takes part in this research study, the participant will be randomized to receive tivozanib by mouth or no therapy. The participant will be given a study drug diary for each treatment if the participant is randomized to the tivozanib group.

Each treatment cycle lasts 28 days (4 weeks). For participants who are randomized to receive tivozanib, the participant will be taking the study drug once per day for 3 weeks followed by a week of rest. The diary will also include special instructions for taking the study drug. The study drug will be taken once a day with plenty of water.

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.

Primary outcomes:
measure: Progression-Free Survival (PFS) Comparison
timeFrame: 2 Years
Secondary outcomes:
measure: Progression-Free Survival (PFS) Evaluation
timeFrame: 2 Years
measure: Overall Survival (OS) Evaluation
timeFrame: 2 Years
measure: Toxicity Rate Comparison
timeFrame: 2 Years
measure: Quality of Life (QOL) Evaluation
timeFrame: 2 Years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Susana Campos, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: