Clinical trial · Interventional
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
NCT00561470CI-TRIAL-00008168VELOURcompletedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Colorectal Neoplasms | Colorectal Neoplasm | ONTOLOGY_EXACT | 0.98 |
| Neoplasm Metastasis | — | UNRESOLVED | — |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) | Drug | Aflibercept | ALIAS |
| FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) | Drug | FOLFIRI Regimen | ALIAS |
| Placebo | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- PLACEBO_COMPARATOR
- label
- Placebo/FOLFIRI
- 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
- interventionNames
- Drug: Placebo
- Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
- type
- EXPERIMENTAL
- label
- Aflibercept/FOLFIRI
- 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
- interventionNames
- Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
- Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Primary outcomes (1)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (9)
- DERIVEDPu T, Peddle AM, Wirapati P, Tsantoulis P, Wu Q, Hong Y, Samuel L, Desai J, Riener M, Saridaki Z, Cunningham D, Tejpar S. Exploratory biomarker analysis of RAS/BRAF somatic mutations and gene expression signatures for predicting treatment effects of aflibercept in the velour trial. NPJ Precis Oncol. 2026 Jan 13;10(1):50. doi: 10.1038/s41698-025-01253-5. PMID 41530374
- DERIVEDWazan LE, Widhibrata A, Liu GS. Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications. Angiogenesis. 2024 Nov;27(4):641-661. doi: 10.1007/s10456-024-09942-8. Epub 2024 Aug 29. PMID 39207600
- DERIVEDLu L, Dercle L, Zhao B, Schwartz LH. Deep learning for the prediction of early on-treatment response in metastatic colorectal cancer from serial medical imaging. Nat Commun. 2021 Nov 17;12(1):6654. doi: 10.1038/s41467-021-26990-6. PMID 34789774
- DERIVEDChau I, Fakih M, Garcia-Alfonso P, Linke Z, Ruiz Casado A, Marques EP, Picard P, Celanovic M, Cartwright T. Safety and Effectiveness of Aflibercept + Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) for the Treatment of Patients with Metastatic Colorectal Cancer (mCRC) in Current Clinical Practice: OZONE Study. Cancers (Basel). 2020 Mar 11;12(3):657. doi: 10.3390/cancers12030657. PMID 32168980
- DERIVEDRuff P, Van Cutsem E, Lakomy R, Prausova J, van Hazel GA, Moiseyenko VM, Soussan-Lazard K, Dochy E, Magherini E, Macarulla T, Papamichael D. Observed benefit and safety of aflibercept in elderly patients with metastatic colorectal cancer: An age-based analysis from the randomized placebo-controlled phase III VELOUR trial. J Geriatr Oncol. 2018 Jan;9(1):32-39. doi: 10.1016/j.jgo.2017.07.010. Epub 2017 Aug 12. PMID 28807738
- DERIVEDStanel SC, Sjoberg J, Salmonson T, Foggi P, Caleno M, Melchiorri D, Gravanis I, Tzogani K, Pignatti F. European Medicines Agency approval summary: Zaltrap for the treatment of patients with oxaliplatin-resistant metastatic colorectal cancer. ESMO Open. 2017 May 2;2(2):e000190. doi: 10.1136/esmoopen-2017-000190. eCollection 2017.