Clinical trial NCT00574275: Aflibercept Compared to Placebo in Term of Efficacy in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer
Official title: A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pancreatic Neoplasm
Keywords: metastatic pancreatic cancer
angiogenesis inhibitor
gemcitabine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2007-12-17
Enrollment: 546
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

* Cytologically or histologically confirmed evidence of epithelial cancer (adenocarcinoma) of the exocrine pancreas
* Metastatic disease
* No prior chemotherapy for pancreatic disease
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
* Adequate renal, liver and bone marrow functions

Exclusion Criteria:

* Less than 42 days elapsed from prior major surgery (28 days from other prior surgery) to the time of randomization
* Prior treatment with anti-VEGF or VEGF-Receptor-inhibitors
* Uncontrolled hypertension
* Pregnancy or breastfeeding
* Participant with reproductive potential (M/F) without effective method of contraception

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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From the first randomization until the end of study data cutoff date (approximately 2 years)
Secondary outcomes:
measure: Progression Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors [RECIST] Criteria
timeFrame: From the first randomization until the end of study data cutoff date (approximately 2 years)
measure: Objective Response Rate (ORR) Assessed by the Investigators According to RECIST Criteria
timeFrame: From the first randomization until the end of the study data cutoff date (approximately 2 years)
measure: Clinical Benefit
timeFrame: From the first randomization until the end of the study data cutoff date (approximately 2 years)
measure: Safety-Number of Participants With Adverse Events (AE)
timeFrame: up to 30 days after treatment discontinuation. SAEs and related AEs were followed till resolved or stabilized.
measure: Number of Participants With Anti-drug Antibodies
timeFrame: Up to 90 days post last dose of study drug
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Administrative Office
city: Wien
country: Austria
facility: Sanofi-Aventis Administrative Office
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Sofia
country: Bulgaria
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: Santafe de Bogota
country: Colombia
facility: Sanofi-Aventis Administrative Office
city: Nikosia
country: Cyprus
facility: Sanofi-Aventis Administrative Office
city: Praha
country: Czech Republic
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Athens
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Mumbai
country: India
facility: Sanofi-Aventis Administrative Office
city: Milano
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Mexico
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Puerto Rico
country: Puerto Rico
facility: Sanofi-Aventis Administrative Office
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Administrative Office
city: Brastislava
country: Slovakia
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013 Aug;49(12):2633-42. doi: 10.1016/j.ejca.2013.04.002. Epub 2013 Apr 30.