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)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Neoplasm Metastasis; Colorectal Neoplasms

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

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT00561470

EFC10262

EudraCT 2007-000820-42

Details and patient eligibility

About

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.

Full 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

Enrollment: 1,226 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Participants who met the following main selection criteria were included in the study.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,226 participants in 2 patient groups, including a placebo group

Placebo/FOLFIRI

Placebo Comparator group

Description:

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

Treatment:

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

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

Drug: Placebo

Aflibercept/FOLFIRI

Experimental group

Description:

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

Treatment:

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

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

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