Clinical trial NCT00396591: AVE0005 (VEGF Trap) in Patients With Recurrent Symptomatic Malignant Ascites
Official title: A Multicenter, Open-label, Single-arm Study of the Efficacy and Safety of Intravenous AVE0005 (VEGF Trap) Administered Every 2 Weeks in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Keywords: Ovarian cancer
malignant ascites
angiogenesis
angiogenesis inhibition
VEGF-Trap fusion recombinant protein
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2006-11-07
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to compare the time between paracenteses before and after administration of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) in ovarian cancer participants with symptomatic malignant ascites.

The secondary objectives were to further assess efficacy and safety of Aflibercept treatment, and the exploratory objectives were to assess pharmacokinetics, immunogenicity and health-related quality of life.

Detailed description: The study consisted of:

* A 30-day screening phase prior to Day 1
* Day 1 registration and pre-treatment paracentesis
* Aflibercept administration within 1-day of registration
* Two-week study treatment cycles (for efficacy data, the cut-off date was 6 months post-registration
* A 60-day post-treatment follow-up phase

During the study, participants were treated with Aflibercept study treatment through the duration of the study unless they met one the following criteria for discontinuation:

* Participant (or legal representative) chose to withdraw from treatment
* The investigator or sponsor thought that continuation of the study would be detrimental to the participants well-being
* Participant had intercurrent illness that prevented further administration of investigational product (IP)
* Participant had more than 2 IP dose reductions
* Participant had unacceptable adverse events (AEs)
* Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset angina, or worsening of preexisting angina
* Participant required surgical intervention for intestinal obstruction or gastrointestinal perforation

Eligibility criteria: Participants that met the following criteria were eligible.

Inclusion Criteria:

* Symptomatic malignant ascites resulting from advanced ovarian epithelial cancer (including fallopian tube and primary peritoneal adenocarcinoma) that required at least 3 previous therapeutic paracenteses at a frequency of 1 to 4 paracenteses per month for management.
* Platinum resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance.
* Topotecan- and/or liposomal doxorubicin-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance.

Exclusion Criteria:

* Peritoneovenous or other type of shunt that was placed for the management of ascites
* Prior treatment with a VEGF or VEGF receptor inhibitor
* Uncontrolled hypertension

The above information is not intended to contain all considerations relevant to participation in a clinical trial.

Primary outcomes:
measure: Percentage of Participants With a Repeat Paracentesis Response (RPR)
timeFrame: up to 2 years post-registration
Secondary outcomes:
measure: Time to Repeat Paracentesis (TRP)
timeFrame: up to 6 months from registration
measure: 60-day Frequency of Paracentesis (FOP)
timeFrame: up to 60 days post-registration
measure: Progression-free Survival (PFS) Time
timeFrame: up to 6 months post-registration
measure: Overall Survival (OS) Time
timeFrame: up to 6 months post-registration
measure: Number of Participants With a Positive Anti-drug Antibody Response
timeFrame: up to 60 days after the last dose of treatment
measure: Safety - Number of Participants With Adverse Events (AE)
timeFrame: up to 60 days after last dose of treatment (approximately 2 years), or until TEAE was resolved or stabilized
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Milano
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: ICD
role: STUDY_DIRECTOR
References:
citation: Colombo N, Mangili G, Mammoliti S, Kalling M, Tholander B, Sternas L, Buzenet G, Chamberlain D. A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites. Gynecol Oncol. 2012 Apr;125(1):42-7. doi: 10.1016/j.ygyno.2011.11.021. Epub 2011 Nov 21.