Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

NCT ID: NCT00327444

Last Updated: 2013-01-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2009-10-31

Brief Summary

This study was designed to characterize the effect of aflibercept in participants with advanced chemoresistant ovarian cancer.

Primary objective: Compare the effect of aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) to placebo treatment on repeat paracentesis in symptomatic malignant ascites in participants with advanced ovarian cancer

Secondary objectives: Safety, tolerability, paracentesis-related parameters, participant-reported outcome.

Detailed Description

The study included:

• A Thirty (30)-day screening phase
• The double blind treatment period for a minimum of 60 days. Day 1 of the double-blind treatment period was defined as the date of the qualifying paracentesis (ie, withdrawal of >= 1 Liter of ascitic fluid). Participants were randomized after adequate recovery from the qualifying paracentesis (The first dose was administered on Day 1 or Day 2).
• The optional open-label extension (until treatment discontinuation criteria were met)
• A posttreatment follow-up phase lasting 60 days.

Criteria for discontinuation included:

1. Participant or his legally authorized representative request discontinuation

2. In the Investigator's opinion, continuation of treatment would be detrimental to the participant's well being, such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations

3. Sponsor request

4. Intercurrent illness that prevented further administration of investigational product(IP)

5. More than 2 IP dose reductions

6. Unacceptable adverse events (AE) not manageable by symptomatic therapy, dose delay, or dose modification

7. Arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of preexisting angina

8. Radiographic evidence of intestinal obstruction (for example, dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (for example, presence of extraluminal gas) requiring surgical intervention

Conditions

Ovarian Neoplasms; Ascites

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Participants with advanced ovarian cancer administered placebo in the double-blind (DB) period.

In the open-label (OL) period, participants had the option to receive aflibercept or be withdrawn from the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.

aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

Intervention Type: DRUG

4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the OL period.

Aflibercept

Participants with advanced ovarian cancer administered aflibercept in the double-blind (DB) period.

In the open-label (OL) period, participants had the option to continue to receive aflibercept or be withdrawn from the study.

Group Type: EXPERIMENTAL

aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

Intervention Type: DRUG

4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.

aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

Intervention Type: DRUG

4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the OL period.

Interventions

aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.

Intervention Type: DRUG

Placebo

Placebo was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.

Intervention Type: DRUG

aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the OL period.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Advanced ovarian epithelial cancer, treated with paracentesis
• Platinum-resistant, and topotecan-resistant and/or liposomal doxorubicin-resistant disease;
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2.

Exclusion Criteria

• Pseudomyxoma peritonei or peritoneal mesothelioma;
• Transudative ascites;
• Peritoneovenous or other shunt placed for malignant ascites management;
• Recent (<6 months) cardiovascular event (pulmonary embolus, myocardial infarction, stroke) or gastrointestinal disease (ulcer, hepatic cirrhosis);
• Known brain metastases;
• Uncontrolled hypertension;
• Recent treatment with chemotherapy, surgery or radiotherapy;
• Prior treatment with VEGF or VEGFR inhibitor.

The above information is not intended to contain all considerations relevant to participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter GOTLIEB

Role: PRINCIPAL_INVESTIGATOR

Director of Gynecologic Oncology and Colposcopy Associate Professor of Oncology, McGill University - Montreal - Quebec Canada

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Sanofi-Aventis Administrative Office

Vienna, , Austria

Sanofi-Aventis Administrative Office

Diegem, , Belgium

Sanofi-Aventis Administrative Office

Laval, , Canada

Sanofi-Aventis Administrative Office

Budapest, , Hungary

Sanofi-Aventis Administrative Office

Mumbai, , India

Sanofi-Aventis Administrative Office

Netanya, , Israel

Sanofi-Aventis Administrative Office

Barcelona, , Spain

Sanofi-Aventis Administrative Office

Guildford Surrey, , United Kingdom

Countries

United States; Austria; Belgium; Canada; Hungary; India; Israel; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37185961 (View on PubMed)

Gotlieb WH, Amant F, Advani S, Goswami C, Hirte H, Provencher D, Somani N, Yamada SD, Tamby JF, Vergote I. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol. 2012 Feb;13(2):154-62. doi: 10.1016/S1470-2045(11)70338-2. Epub 2011 Dec 20.

Reference Type: DERIVED

PMID: 22192729 (View on PubMed)

Other Identifiers

EudraCT : 2005-005026-31

Identifier Type: -

Identifier Source: secondary_id

AVE0005A /3001

Identifier Type: -

Identifier Source: secondary_id

EFC6125

Identifier Type: -

Identifier Source: org_study_id