NCT00561470

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

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,226 (actual)
• Sponsor: Sanofi · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Participants were * randomized at baseline (treatment was initiated with 3 days of randomization) * administered treatment in cycles of 14-days till a study withdrawal criterion was met * followed up 30 days after discontinuation of treatment, and every 8 weeks until death or end of study. The criteria for discontinuation of study treatment for a participant are: * 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 due to * disease progression * unacceptable AEs * intercurrent illnesses * non-compliance to the study protocol * participant was lost to follow-up * participant was unblinded for the investigational treatment

Conditions

• Colorectal Neoplasms
• Neoplasm Metastasis

Interventions

Type	Name	Description
DRUG	Placebo	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
DRUG	Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)	4 mg/kg of Aflibercept was administered IV over 1 hour on Day 1, every 2 weeks.
DRUG	FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)	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
DRUG	FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)	The FOLFIRI regimen was initiated immediately after Aflibercept 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

Timeline

• Start date: 2007-11-01
• Primary completion: 2011-02-01
• Completion: 2012-06-01
• First posted: 2007-11-21
• Last updated: 2012-09-28
• Results posted: 2012-09-28

Locations

221 sites across 28 countries: United States, Argentina, Australia, Austria, Belgium, Brazil, Chile, Czechia, Denmark, Estonia, France, Germany, Greece, Italy, Netherlands, New Zealand, Norway, Poland, Puerto Rico, Romania, Russia, South Africa, South Korea, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom