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

Ovarian Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00327444
• Other study ID #: EFC6125
• Secondary ID: EudraCT : 2005-0
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 16, 2006
• Last updated: November 30, 2012
• Start date: July 2006
• Est. completion date: October 2009

Study information

• Verified date: July 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Ascites
• Ovarian Neoplasms

Intervention

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

Locations

Country	Name	City	State
Austria	Sanofi-Aventis Administrative Office	Vienna
Belgium	Sanofi-Aventis Administrative Office	Diegem
Canada	Sanofi-Aventis Administrative Office	Laval
Hungary	Sanofi-Aventis Administrative Office	Budapest
India	Sanofi-Aventis Administrative Office	Mumbai
Israel	Sanofi-Aventis Administrative Office	Natanya
Spain	Sanofi-Aventis Administrative Office	Barcelona
United Kingdom	Sanofi-Aventis Administrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Repeat Paracentesis (TRP)	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	No
Secondary	Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM)	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	No
Secondary	60-Day Frequency of Paracentesis (FOP)	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	No
Secondary	Plasma Levels of Free and VEGF-bound Aflibercept	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	No