NCT00561470|CompletedPhase 3ResultsDMC

Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen

VELOUR

A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients With Metastatic Colorectal Cancer (MCRC) Treated With Irinotecan / 5-FU Combination (FOLFIRI) After Failure of an Oxaliplatin Based Regimen

Sanofi ClinicalTrials.gov

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2 other identifiers

EFC10262EudraCT 2007-000820-42

Study Type

interventional

Target

1,226

Locations

26 countries

Sites

218

Timeline

RegisteredNov 2007

StartedNov 2007

CompletionJun 2012

Brief Summary

The main objective of the study was to evaluate the effectiveness of aflibercept (versus placebo) in increasing the overall survival in participants with metastatic colorectal cancer treated with FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) and that have previously failed an oxaliplatin based treatment for metastatic disease. The secondary objectives were to compare progression-free survival, to evaluate overall response rate, to evaluate the safety profile, to assess immunogenicity of intravenous (IV) aflibercept, and to assess pharmacokinetics of IV aflibercept in both treatment arms.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

1,226

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Nov 2007

Longer than P75 for phase_3

Geographic Reach

26 countries

218 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.6 years study duration

Study Start

First participant enrolled

November 1, 2007

Completed

19 days until next milestone

First Submitted

Initial submission to the registry

November 20, 2007

Completed

1 day until next milestone

First Posted

Study publicly available on registry

November 21, 2007

Completed

3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2011

Completed

1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed

4 months until next milestone

Results Posted

Study results publicly available

September 28, 2012

Completed

Last Updated

September 28, 2012

Status Verified

March 1, 2012

Enrollment Period

3.3 years

First QC Date

November 20, 2007

Results QC Date

August 17, 2012

Last Update Submit

September 27, 2012

Conditions

Colorectal Neoplasms Neoplasm Metastasis

Keywords

colorectal cancermetastaticanti-angiogenicirinotecan5-FUFOLFIRI

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS)
Overall Survival was the time interval from the date of randomization to the date of death due to any cause. Once disease progression was documented, participants were followed every 2 months for survival status, until death or until the study cutoff date, whichever came first. The final data cutoff date for the analysis of OS was the date when 863 deaths had occurred (07 February 2011). OS was estimated using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model.
From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years)

Secondary Outcomes (4)

Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)
From the date of the first randomization until the occurrence of 561 OS events, 06 May 2010 (approximately 30 months)
Overall Objective Response Rate (ORR) Based on the Tumor Assessment by the Independent Review Committee (IRC) as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria
From the date of the first randomization until the study data cut-off date, 06 May 2010 (approximately 30 months)
Number of Participants With Adverse Events (AE)
From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized
Immunogenicity Assessment: Number of Participants With Positive Sample(s) in the Anti-drug Antibodies (ADA) Assay and in the Neutralizing Anti-drug Antibodies (NAb) Assay
Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo

Study Arms (2)

Placebo/FOLFIRI

PLACEBO COMPARATOR

Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met

Drug: PlaceboDrug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

Aflibercept/FOLFIRI

EXPERIMENTAL

Participants with Metastatic Colorectal Cancer administered Aflibercept followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) starting on Day 1 of a 2-week cycle until a treatment discontinuation criterion was met

Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)

Interventions

PlaceboDRUG

4 mg/kg of sterile aqueous buffered vehicle (pH 6.0) was administered intra venously (IV) over 1 hour on Day 1, every 2 weeks

Placebo/FOLFIRI

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

4 mg/kg of Aflibercept was administered IV over 1 hour on Day 1, every 2 weeks.

Aflibercept/FOLFIRI

FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)DRUG

The FOLFIRI regimen was initiated immediately after Placebo administration on Day 1 The FOLFIRI regimen included: * 180 mg/m² Irinotecan (Campto®, Camptosar®) IV infusion over 90 minutes and dl leucovorin 400 mg/m² (200 mg/m² for the l-isomer form) IV infusion over 2 hours, followed by: * 5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by: * 5-FU 2400 mg/m² continuous IV infusion over 46-hours

Placebo/FOLFIRI

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Histologically or cytologically proven adenocarcinoma of the colon or rectum
Metastatic disease that is not amenable to potentially curative treatment
One and only one prior line of treatment for metastatic disease. This prior line should be an oxaliplatin based chemotherapy (participants who relapse within 6 months of completion of oxaliplatin based adjuvant chemotherapy are eligible)
Prior treatment with bevacizumab is permitted.

You may not qualify if:

Prior therapy with irinotecan
Eastern Cooperative Oncology Group performance status \>2
The above information is not intended to contain all considerations relevant to participation in a clinical trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (221)

Sanofi-Aventis Investigational Site Number 840119

Birmingham, Alabama, 35203, United States

Location

Sanofi-Aventis Investigational Site Number 840074

Muscle Shoals, Alabama, 35661, United States

Location

Sanofi-Aventis Investigational Site Number 840093

Hot Springs, Arizona, 71913, United States

Location

Sanofi-Aventis Investigational Site Number 840080

Anaheim, California, 92801, United States

Location

Sanofi-Aventis Investigational Site Number 840076

Fountain Valley, California, 92708, United States

Location

Sanofi-Aventis Investigational Site Number 840120

Fountain Valley, California, 92708, United States

Location

Sanofi-Aventis Investigational Site Number 840073

Greenbrae, California, 94904-2007, United States

Location

Sanofi-Aventis Investigational Site Number 840101

Hayward, California, 94545, United States

Location

Sanofi-Aventis Investigational Site Number 840046

La Jolla, California, 92037, United States

Location

Sanofi-Aventis Investigational Site Number 840116

Loma Linda, California, 92354, United States

Location

Sanofi-Aventis Investigational Site Number 840048

Long Beach, California, 90813, United States

Location

Sanofi-Aventis Investigational Site Number 840201

Oakland, California, 94611, United States

Location

Sanofi-Aventis Investigational Site Number 840901

Roseville, California, 95678, United States

Location

Sanofi-Aventis Investigational Site Number 840042

Sacramento, California, 95816, United States

Location

Sanofi-Aventis Investigational Site Number 840301

Sacramento, California, 95825, United States

Location

Sanofi-Aventis Investigational Site Number 840112

Salinas, California, 93901-3906, United States

Location

Sanofi-Aventis Investigational Site Number 840006