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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.
Placebo was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.
4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the OL period.
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
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.
Time frame: From Day 1 up to 6 months from randomization
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 (-).
Time frame: From Day 1 up to 60 days from randomization to the first postrandomization paracentesis
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.
Time frame: From Day 1 up to 60 days from randomization
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.
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Enrollment
58
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
Time frame: Following every biweekly treatment administration up to 60 days after treatment discontinuation