Clinical trial NCT00327171
Conditions: Neoplasms Cancer of the Ovary
Keywords: ovarian cancer angiogenesis angiogenesis inhibition VEGF-Trap fusion recombinant protein Cancer and other neoplasms
Sponsor: Sanofi
Start date: 2006-05-01; Completion date: 2010-03-01
Enrollment: 218 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma receiving aflibercept.

The primary objective was to compare the objective response rate of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered intravenously (IV) every 2 weeks with historical control in participants with advanced ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant to platinum and topotecan and/or liposomal doxorubicin.

The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential biological and pharmacogenomic markers of study drug activity, and health-related quality of life.

This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the IRC reviewed data is reported for this study.

Detailed description:
The study included:

* A screening period for 21 days
* Randomization at baseline (Treatment was initiated with 5 days of randomization)
* A treatment period with 14-day study treatment cycles until a study withdrawal criterion was met
* A follow-up period up to 60 days after the end of treatment

Withdrawal criteria that led to treatment discontinuation were:

* The participant or their legally authorized representative requested to withdraw
* In the investigator's opinion, continuation of the study would be detrimental to the participant's well being, due to reasons such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations.
* A specific request by the Sponsor
* Participant had intercurrent illness that prevented further administration of study treatment
* Participant had more than 2 aflibercept dose reductions
* Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of pre-existing angina
* Participant had radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention
* Participant was lost to follow-up

After discontinuing treatment, participants remained on the study until the last post-treatment visit or until recovery of drug related toxicities, whichever was later.

Arms: arm 1: Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept. arm 2: Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept.
Interventions: intervention 1: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) intervention 2: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Intervention descriptions: intervention 1: Aflibercept 4.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level ( to 2.0 mg/kg) or 2 dose levels (to 1.0 mg/kg) in case of uncontrolled hypertension or urinary protein \>3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment. intervention 2: Aflibercept 2.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level (to 1.0 mg/kg) or 2 dose levels (to 0.5 mg/kg) in case of uncontrolled hypertension or urinary protein \>3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Protocol documents: