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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Time to Repeat Paracentesis (TRP)
Study Overview
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:
- Participant or his legally authorized representative request discontinuation
- 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
- Sponsor request
- Intercurrent illness that prevented further administration of investigational product(IP)
- More than 2 IP dose reductions
- Unacceptable adverse events (AE) not manageable by symptomatic therapy, dose delay, or dose modification
- Arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of preexisting angina
- 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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Placebo (Drug)
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.
Intervention: aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
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.
Intervention: aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM)(From Day 1 up to 60 days from randomization to the first postrandomization paracentesis)
- 60-Day Frequency of Paracentesis (FOP)(From Day 1 up to 60 days from randomization)
- Plasma Levels of Free and VEGF-bound Aflibercept(Following every biweekly treatment administration up to 60 days after treatment discontinuation)