Clinical trial NCT00561470
Conditions: Colorectal Neoplasms Neoplasm Metastasis
Keywords: colorectal cancer metastatic anti-angiogenic irinotecan 5-FU FOLFIRI
Sponsor: Sanofi
Start date: 2007-11-01; Completion date: 2012-06-01
Enrollment: 1226 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

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

Arms: arm 1: 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 arm 2: 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
Interventions: intervention 1: Placebo intervention 2: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) intervention 3: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) intervention 4: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Intervention descriptions: intervention 1: 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 intervention 2: 4 mg/kg of Aflibercept was administered IV over 1 hour on Day 1, every 2 weeks. intervention 3: 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 intervention 4: 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

Protocol documents: