Study of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The primary objective of the study is to estimate the progression-free survival rate at 12 months for the two arms of the study. Secondary objectives include the evaluation of overall objective response rate to treatment, progression-free survival, overall survival, safety and documentation of potential immunogenicity of aflibercept. This study was a non-comparative randomized trial and was not powered for a comparison of any of the efficacy endpoints. Rather, the aim of the trial was to get, for all endpoints, an estimation of the efficacy and safety of aflibercept combined with a modified FOLFOX6 regimen. In such type of non-comparative randomized trial, the control FOLFOLX6 arm was intended to only act as a check on the similarity of the current patients to the historical controls with respect to clinical outcome when given FOLFOX6 treatment.

Official Title
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Randomized, Multinational, Study Of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Neoplasms, Neoplasm Metastasis

Intervention / Treatment
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* Drug: aflibercept
* Drug: oxaliplatin
* Drug: 5-FU
* Drug: Folinic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven adenocarcinoma of the colon or the rectum Metastatic disease not amenable to potentially curative treatment Exclusion Criteria: Prior therapy for metastatic cancer of the colon or the rectum Prior treatment with angiogenesis inhibitors The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: mFOLFOX6 only<br>modified FOLFOX6 chemotherapy regimen | Drug: oxaliplatin<br>* administration: IV infusion<br>Drug: 5-FU<br>* administration: IV infusion<br>Drug: Folinic Acid<br>* administration: IV infusion<br>|
| Experimental: mFOLFOX6 + aflibercept<br>modified FOLFOX6 chemotherapy regimen in combination with aflibercept | Drug: aflibercept<br>* administration: IV infusion<br>* Other names: AVE0005;Drug: oxaliplatin<br>* administration: IV infusion<br>Drug: 5-FU<br>* administration: IV infusion<br>Drug: Folinic Acid<br>* administration: IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Rate at 12 Months | PFS rate at 12 months was defined as the percentage of patients alive without disease progression at 12 months after randomization. The primary efficacy analysis was based on assessment by the Independent Review Committee (IRC). The study was not powered for comparison of PFS rate at 12 months between the two arms (non-comparative, open-label study). Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was defined as the time from the date of randomization to the date of tumor progression or death from any cause, whichever occurred first. PFS was based on tumor assessment by the Independent Review Committee (IRC). PFS was estimated from Kaplan-Meier Curves. The study was not powered for comparison of PFS between the two arms (non-comparative, open-label study). Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. | From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months) | 
| Overall Objective Response Rate (ORR) | Summary of overall objective response rate based on tumor assessment by the Independent Review Committee (IRC) as per Response Evaluation Criteria in Solid Tumours (RECIST) criteria. ORR was defined as the proportion of patients with confirmed Complete Response (CR) or confirmed Partial Response (PR) relative to the total number of patients in the analysis population. Per RECIST v 1.0 target lesions evaluation and assessed by tumor imaging: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The study was not powered for comparison of ORR between the two arms (non-comparative, open-label study). | From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months) | 
| Overall Survival (OS) | Overall survival was defined as the time from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earliest between the last date the patient was known to be alive and the study cutoff date. The study was not powered for comparison of OS between the two arms (non-comparative, open-label study). | From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months) | 
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | Summary of treatment-emergent adverse events in the safety population. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used in this study to grade the severity of AEs. | From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized | 
| Immunogenicity of Intravenous (IV) Aflibercept | The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept. | Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angiogenesis, Colon cancer, Rectal cancer, Oxaliplatin