Tivozanib As Maintenance Therapy In GYN

NCT01972516 | Terminated Phase 2 Results DMC

• 1 other identifier: 13-375
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Keywords

Platinum-Sensitive; Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; High-grade Serous

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) Comparison

  To compare progression-free survival of maintenance therapy with Tivozanib against standard of care in patients with ovarian, fallopian tube or primary peritoneal carcinoma who have achieved a complete response following therapy for platinum sensitive disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)

  2 Years

Secondary Outcomes (4)

• Progression-Free Survival (PFS) Evaluation

  2 Years

• Overall Survival (OS) Evaluation

  2 Years

• Toxicity Rate Comparison

  2 Years

• Quality of Life (QOL) Evaluation

  2 Years

Study Arms (2)

Tivozanib

EXPERIMENTAL

Tivozanib hydrochloride will be administered orally, at a dose of 1.5 mg/day, beginning on Day 1 of Cycle 1. Subjects will receive tivozanib hydrochloride once daily for 3 weeks followed by 1 week off treatment. One cycle is defined as 4 weeks. Cycles will be repeated every 4 weeks in the absence of disease progression or unacceptable toxicities.

Drug: Tivozanib

Standard Care

NO INTERVENTION

Participants in the non-interventional arm will not receive study treatment, and will receive standard clinical observation and study assessments. Patients will continue to be observed in the absence of disease progression or unacceptable toxicities.

Interventions

Tivozanib DRUG

Also known as: Tivozanib hydrochloride, AV-951

Tivozanib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Comprehensive Cancer Network: collaborator
• AVEO Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

tivozanib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Limitations and Caveats

Terminated early due to low accrual.

Results Point of Contact

• Title: Susana Campos, MD
• Organization: Dana-Farber Cancer Institute

susana_campos@dfci.harvard.edu

617-632-5269

Study Officials

• Susana Campos, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: October 30, 2013
• Study Start: November 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: January 1, 2016
• Last Updated: June 5, 2017
• Results First Posted: August 24, 2016

Record last verified: 2017-05

Locations

US (1)