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

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00327444
First received: May 16, 2006
Last updated: November 30, 2012
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Ovarian Neoplasms
Ascites
Drug: aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Time to Repeat Paracentesis (TRP) [ Time Frame: From Day 1 up to 6 months from randomization ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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 (-).


  • 60-Day Frequency of Paracentesis (FOP) [ Time Frame: From Day 1 up to 60 days from randomization ] [ Designated as safety issue: No ]
    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.

  • Plasma Levels of Free and VEGF-bound Aflibercept [ Time Frame: Following every biweekly treatment administration up to 60 days after treatment discontinuation ] [ Designated as safety issue: No ]

    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.



Enrollment: 58
Study Start Date: July 2006
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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.

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00327444

Locations
United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Austria
Sanofi-Aventis Administrative Office
Vienna, Austria
Belgium
Sanofi-Aventis Administrative Office
Diegem, Belgium
Canada
Sanofi-Aventis Administrative Office
Laval, Canada
Hungary
Sanofi-Aventis Administrative Office
Budapest, Hungary
India
Sanofi-Aventis Administrative Office
Mumbai, India
Israel
Sanofi-Aventis Administrative Office
Natanya, Israel
Spain
Sanofi-Aventis Administrative Office
Barcelona, Spain
United Kingdom
Sanofi-Aventis Administrative Office
Guildford Surrey, United Kingdom
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Principal Investigator: Walter GOTLIEB Director of Gynecologic Oncology and Colposcopy Associate Professor of Oncology, McGill University - Montreal - Quebec Canada
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00327444     History of Changes
Other Study ID Numbers: EFC6125, EudraCT : 2005-005026-31, AVE0005A /3001
Study First Received: May 16, 2006
Results First Received: August 17, 2012
Last Updated: November 30, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Sanofi:
Ovarian neoplasm
Ascites
Angiogenesis inhibitor
Vascular Endothelial Growth Factor A
Recombinant fusion protein

Additional relevant MeSH terms:
Ascites
Neoplasms
Ovarian Neoplasms
Pathologic Processes
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 22, 2014