Aflibercept Compared to Placebo in Term of Efficacy in Patients Treated With Gemcitabine for Metastatic Pancreatic Cancer

NCT ID: NCT00574275

Last Updated: 2016-06-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 546 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2010-11-30

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

Conditions

Pancreatic Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo and Gemcitabine

Participants with metastatic pancreatic cancer administered Placebo and 1000 mg/m\^2 Gemcitabine.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle

Gemcitabine

Intervention Type: DRUG

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.

Aflibercept and Gemcitabine

Participants with metastatic pancreatic cancer administered 4 mg/kg Aflibercept and 1000 mg/m\^2 Gemcitabine.

Group Type: EXPERIMENTAL

Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

Intervention Type: DRUG

4 mg/kg was administered intravenously (IV) over 1 hour once every 2 weeks, on Days 1 and 15 of each 28-day cycle.

Gemcitabine

Intervention Type: DRUG

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.

Interventions

Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

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 Type: DRUG

Placebo

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 Type: DRUG

Gemcitabine

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.

Intervention Type: DRUG

Other Intervention Names

Gemzar

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Sanofi-Aventis Administrative Office

Buenos Aires, , Argentina

Sanofi-Aventis Administrative Office

Vienna, , Austria

Sanofi-Aventis Administrative Office

Diegem, , Belgium

Sanofi-Aventis Administrative Office

Sofia, , Bulgaria

Sanofi-Aventis Administrative Office

Laval, , Canada

Sanofi-Aventis Administrative Office

Santiago, , Chile

Sanofi-Aventis Administrative Office

Bogotá, , Colombia

Sanofi-Aventis Administrative Office

Nicosia, , Cyprus

Sanofi-Aventis Administrative Office

Prague, , Czechia

Sanofi-Aventis Administrative Office

Paris, , France

Sanofi-Aventis Administrative Office

Berlin, , Germany

Sanofi-Aventis Administrative Office

Athens, , Greece

Sanofi-Aventis Administrative Office

Budapest, , Hungary

Sanofi-Aventis Administrative Office

Mumbai, , India

Sanofi-Aventis Administrative Office

Milan, , Italy

Sanofi-Aventis Administrative Office

México, , Mexico

Sanofi-Aventis Administrative Office

Warsaw, , Poland

Sanofi-Aventis Administrative Office

San Juan, , Puerto Rico

Sanofi-Aventis Administrative Office

Bucharest, , Romania

Sanofi-Aventis Administrative Office

Moscow, , Russia

Sanofi-Aventis Administrative Office

Brastislava, , Slovakia

Sanofi-Aventis Administrative Office

Barcelona, , Spain

Sanofi-Aventis Administrative Office

Geneva, , Switzerland

Countries

United States; Argentina; Austria; Belgium; Bulgaria; Canada; Chile; Colombia; Cyprus; Czechia; France; Germany; Greece; Hungary; India; Italy; Mexico; Poland; Puerto Rico; Romania; Russia; Slovakia; Spain; Switzerland

References

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.

Reference Type: RESULT

PMID: 23642329 (View on PubMed)

Other Identifiers

EudraCT 2007-003476-19

Identifier Type: -

Identifier Source: secondary_id

EFC10547

Identifier Type: -

Identifier Source: org_study_id