Conditions: Pancreatic Neoplasm
Keywords: metastatic pancreatic cancer angiogenesis inhibitor gemcitabine
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 546
Healthy volunteers: no

Brief summary:
The main objective of the study was to evaluate the effectiveness of aflibercept treatment by comparison to placebo in increasing the overall survival (OS) in participants with metastatic pancreatic cancer, treated with gemcitabine.

The secondary objectives were to evaluate progression free survival, clinical benefit, overall response, safety and immunogenicity of aflibercept, in the two treatment arms (Arm 1: Aflibercept and Gemcitabine; Arm 2: Placebo and Gemcitabine).

The study included an interim analysis of OS. In accordance with the study protocol, an interim analysis was performed for the purpose of futility and overwhelming efficacy. On the basis of the interim analysis, the Data Monitoring Committee (DMC) recommended that this study be terminated for futility based on predefined boundary rules.

Detailed description:
The study included:

* A screening visit of up to 21 days prior to randomization
* Randomization at baseline
* A Treatment period (initiated within 3 days of randomization), which included 28-day treatment cycles in both arms until predefined treatment discontinuation criteria were met
* A follow-up visit 30 days after discontinuation of treatment,
* A post study treatment follow-up period until death or the study cutoff date.

The criteria for treatment discontinuation were:

* Participant (or legal representative) chose to withdraw from treatment
* The investigator thought that continuation of the study would be detrimental to the participants well-being, such as:

  * Disease progression
  * Unacceptable AEs not manageable by symptomatic therapy, dose delay, or dose modification
  * Intercurrent illness that prevented further administration of study treatment
  * Noncompliance with the study protocol
* Participant was lost to follow-up
* Unblinding of the participant's investigational treatment

Arms:
arm 1: Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m\^2 Gemcitabine. arm 2: Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m\^2 Gemcitabine.

Interventions: intervention 1: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) intervention 2: Placebo intervention 3: Gemcitabine
Intervention descriptions: intervention 1: 4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle. intervention 2: 4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle intervention 3: 1000 mg/m\^2 administered IV over 30 minutes on Days 1, 8, 15, and 22 of Cycle 1 (28 days), and then Days 1, 8, and 15 of subsequent 28-day cycles.

Protocol document: