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Phase 3 N=1,226 Randomized Triple-blind Treatment

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

Colorectal Neoplasms · Neoplasm Metastasis

Enrolled (actual)
1,226
Serious AEs
40.5%
Results posted
Sep 2012
Primary outcome: Primary: Overall Survival (OS) — 12.06; 13.50 months — p=0.0032

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Placebo (Drug); Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug); FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Sanofi
Primary completion
Feb 2011

Outcome Measures

OutcomeResultp-value
PRIMARY
Overall Survival (OS)
12.06; 13.50 0.0032 sig
SECONDARY
Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)
4.67; 6.90 0.00007 sig
SECONDARY
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
11.1; 19.8 0.0001 sig
SECONDARY
Number of Participants With Adverse Events (AE)
592; 606; 198; 294; 29; 37
SECONDARY
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
18; 8; 2; 1

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.

Eligibility 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00561470). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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