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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 1,226
- Locations
- 221
- Primary Endpoint
- Overall Survival (OS)
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Placebo/FOLFIRI
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
Intervention: Placebo (Drug)
Placebo/FOLFIRI
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
Intervention: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) (Drug)
Aflibercept/FOLFIRI
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
Intervention: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
Aflibercept/FOLFIRI
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
Intervention: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years)
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.
Secondary Outcomes
- 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)