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

Sanofi268 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

268

Conditions

Colorectal Neoplasms Neoplasm Metastasis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (37)

Sanofi-Aventis Investigational Site Number 036004

Douglas, Australia

Sanofi-Aventis Investigational Site Number 036001

Hunter Region Mail Centre, Australia

Sanofi-Aventis Investigational Site Number 036003

Hunter Region Mail Centre, Australia

Sanofi-Aventis Investigational Site Number 276003

Berlin, Germany

Sanofi-Aventis Investigational Site Number 276007

Dresden, Germany

Outcomes

Primary Outcomes

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.

Time frame: 12 months

Secondary Outcomes

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.

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status