Clinical trial NCT00327444: Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Ovarian Neoplasms
Ascites
Keywords: Ovarian neoplasm
Ascites
Angiogenesis inhibitor
Vascular Endothelial Growth Factor A
Recombinant fusion protein
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2006-05-18
Enrollment: 58
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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 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.

Primary outcomes:
measure: Time to Repeat Paracentesis (TRP)
timeFrame: From Day 1 up to 6 months from randomization
Secondary outcomes:
measure: Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM)
timeFrame: From Day 1 up to 60 days from randomization to the first postrandomization paracentesis
measure: 60-Day Frequency of Paracentesis (FOP)
timeFrame: From Day 1 up to 60 days from randomization
measure: Plasma Levels of Free and VEGF-bound Aflibercept
timeFrame: Following every biweekly treatment administration up to 60 days after treatment discontinuation
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Vienna
country: Austria
facility: Sanofi-Aventis Administrative Office
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Mumbai
country: India
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Director of Gynecologic Oncology and Colposcopy Associate Professor of Oncology, McGill University - Montreal - Quebec Canada
name: Walter GOTLIEB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gotlieb WH, Amant F, Advani S, Goswami C, Hirte H, Provencher D, Somani N, Yamada SD, Tamby JF, Vergote I. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol. 2012 Feb;13(2):154-62. doi: 10.1016/S1470-2045(11)70338-2. Epub 2011 Dec 20.