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

November 30, 2012 updated by: Sanofi

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-arm Study of the Effect of Intravenous Aflibercept Administered Every 2 Weeks in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria
        • Sanofi-Aventis Administrative Office
  • Belgium
      • Diegem, Belgium
        • Sanofi-Aventis Administrative Office
  • Canada
      • Laval, Canada
        • Sanofi-Aventis Administrative Office
  • Hungary
      • Budapest, Hungary
        • Sanofi-Aventis Administrative Office
  • India
      • Mumbai, India
        • Sanofi-Aventis Administrative Office
  • Israel
      • Natanya, Israel
        • Sanofi-Aventis Administrative Office
  • Spain
      • Barcelona, Spain
        • Sanofi-Aventis Administrative Office
  • United Kingdom
      • Guildford Surrey, United Kingdom
        • Sanofi-Aventis Administrative Office
  • United States
    • New Jersey
      • Bridgewater, New Jersey, United States, 08807
        • Sanofi-Aventis Administrative Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Participants who met the following criteria were eligible to participate in this study.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: 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.
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 DB period.
Drug: Placebo
Placebo was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.
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.
EXPERIMENTAL: 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.
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 DB period.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Repeat Paracentesis (TRP)
Time Frame: From Day 1 up to 6 months from randomization

TRP was defined as the number of days between the date of randomization and the date of the first post-randomization paracentesis.

For participants who did not undergo a postrandomization paracentesis on study, TRP was calculated from randomization to the end of the double-blind treatment period.
From Day 1 up to 6 months from randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM)
Time Frame: From Day 1 up to 60 days from randomization to the first postrandomization paracentesis

AIM 4 symptoms (abdominal discomfort, abdominal bloating, abdominal pain, and ability to move normally) are scored from 0 to 5, where higher scores represent worst outcomes. An AIM total score ranges from 0-20.

A plot for (The AIM questionnaire total score - Baseline score) versus time were generated. AIM AUC represents the overall improvement (scored positive) if the area is below the baseline value or worsening (scored negative) if the area is above the baseline. AIM AUC for a participant is the sum of individual areas representing improvement (+) or worsening (-).
From Day 1 up to 60 days from randomization to the first postrandomization paracentesis
60-Day Frequency of Paracentesis (FOP)
Time Frame: From Day 1 up to 60 days from randomization
60-Day FOP was defined as the total number of paracenteses performed within the first 60 days after randomization during the double blind treatment period.
From Day 1 up to 60 days from randomization
Plasma Levels of Free and VEGF-bound Aflibercept
Time Frame: Following every biweekly treatment administration up to 60 days after treatment discontinuation

Free aflibercept and VEGF-bound aflibercept plasma concentrations were measured by separate enzyme-linked immunosorbent assay (ELISA). The limit of quantitation of free aflibercept was 15.6 ng/mL, and of VEGF-bound aflibercept was 43.9 ng/mL.

Peak free aflibercept was estimated at the end of Cycle 1 (C1) administration. The median free and VEGF-bound trough concentrations were determined for each participant beyond Cycle 3 (C3), then mean values were estimated from these median values.
Following every biweekly treatment administration up to 60 days after treatment discontinuation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

Investigators

  • Principal Investigator: Walter GOTLIEB, Director of Gynecologic Oncology and Colposcopy Associate Professor of Oncology, McGill University - Montreal - Quebec Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (ACTUAL)

October 1, 2009

Study Completion (ACTUAL)

October 1, 2009

Study Registration Dates

First Submitted

May 16, 2006

First Submitted That Met QC Criteria

May 16, 2006

First Posted (ESTIMATE)

May 18, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

January 1, 2013

Last Update Submitted That Met QC Criteria

November 30, 2012

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EFC6125
  • EudraCT : 2005-005026-31
  • AVE0005A /3001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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