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

Phase 2

Completed

• Conditions: Colorectal Neoplasms; Neoplasm Metastasis
• Interventions: Drug: aflibercept; Drug: oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

• Registration Number: NCT00851084
• Lead Sponsor: Sanofi

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-02-24
• Study First Submitted QC: 2009-02-24
• Study First Posted: 2009-02-25
• Primary Completion: 2011-04
• Study Completion: 2012-01
• Results First Submitted: 2013-02-19
• Results First Submitted QC: 2013-06-21
• Results First Posted: 2013-06-25
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-04
• Last Update Posted: 2016-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 268

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
mFOLFOX6 + aflibercept	aflibercept	modified FOLFOX6 chemotherapy regimen in combination with aflibercept
mFOLFOX6 + aflibercept	oxaliplatin	modified FOLFOX6 chemotherapy regimen in combination with aflibercept
mFOLFOX6 + aflibercept	Folinic Acid	modified FOLFOX6 chemotherapy regimen in combination with aflibercept
mFOLFOX6 only	oxaliplatin	modified FOLFOX6 chemotherapy regimen
mFOLFOX6 only	5-FU	modified FOLFOX6 chemotherapy regimen
mFOLFOX6 only	Folinic Acid	modified FOLFOX6 chemotherapy regimen
mFOLFOX6 + aflibercept	5-FU	modified FOLFOX6 chemotherapy regimen in combination with aflibercept

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) Rate at 12 Months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAE)	From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized	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.
Immunogenicity of Intravenous (IV) Aflibercept	Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status	The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.
Overall Objective Response Rate (ORR)	From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)	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).
Overall Survival (OS)	From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)	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).
Progression Free Survival (PFS)	From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)	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.

Trial Locations

Locations (37)

Sanofi-Aventis Investigational Site Number 036001; 🇦🇺 Hunter Region Mail Centre, Australia

Sanofi-Aventis Investigational Site Number 276001; 🇩🇪 Hannover, Germany

Sanofi-Aventis Investigational Site Number 724002; 🇪🇸 Sabadell, Spain

Sanofi-Aventis Investigational Site Number 410002; 🇰🇷 Daejeon, Korea, Republic of

Sanofi-Aventis Investigational Site Number 410007; 🇰🇷 Goyang-Si, Gyeonggi-Do, Korea, Republic of

Sanofi-Aventis Investigational Site Number 380001; 🇮🇹 Firenze, Italy

Sanofi-Aventis Investigational Site Number 380002; 🇮🇹 Milano, Italy

Sanofi-Aventis Investigational Site Number 380004; 🇮🇹 Torino, Italy

Sanofi-Aventis Investigational Site Number 410006; 🇰🇷 Seoul, Korea, Republic of

Sanofi-Aventis Investigational Site Number 380005; 🇮🇹 Bari, Italy

Sanofi-Aventis Investigational Site Number 410003; 🇰🇷 Busan, Korea, Republic of

Sanofi-Aventis Investigational Site Number 380003; 🇮🇹 Taormina, Italy

Sanofi-Aventis Investigational Site Number 643001; 🇷🇺 Sochi, Russian Federation

Sanofi-Aventis Investigational Site Number 036004; 🇦🇺 Douglas, Australia

Sanofi-Aventis Investigational Site Number 276007; 🇩🇪 Dresden, Germany

Sanofi-Aventis Investigational Site Number 036003; 🇦🇺 Hunter Region Mail Centre, Australia

Sanofi-Aventis Investigational Site Number 276003; 🇩🇪 Berlin, Germany

Sanofi-Aventis Investigational Site Number 276006; 🇩🇪 Homberg, Germany

Sanofi-Aventis Investigational Site Number 276004; 🇩🇪 Mannheim, Germany

Sanofi-Aventis Investigational Site Number 276002; 🇩🇪 Münster, Germany

Sanofi-Aventis Investigational Site Number 276005; 🇩🇪 Recklinghausen, Germany

Sanofi-Aventis Investigational Site Number 410004; 🇰🇷 Cheongju, Korea, Republic of

Sanofi-Aventis Investigational Site Number 410005; 🇰🇷 Daegu, Korea, Republic of

Sanofi-Aventis Investigational Site Number 410001; 🇰🇷 Seoul, Korea, Republic of

Sanofi-Aventis Investigational Site Number 410008; 🇰🇷 Ulsan, Korea, Republic of

Sanofi-Aventis Investigational Site Number 643002; 🇷🇺 Pyatigorsk, Russian Federation

Sanofi-Aventis Investigational Site Number 643005; 🇷🇺 Saint-Petersburg, Russian Federation

Sanofi-Aventis Investigational Site Number 724004; 🇪🇸 Madrid, Spain

Sanofi-Aventis Investigational Site Number 724001; 🇪🇸 Madrid, Spain

Sanofi-Aventis Investigational Site Number 724005; 🇪🇸 Barcelona, Spain

Sanofi-Aventis Investigational Site Number 724007; 🇪🇸 Santiago De Compostela, Spain

Sanofi-Aventis Investigational Site Number 826004; 🇬🇧 Leeds, United Kingdom

Sanofi-Aventis Investigational Site Number 724003; 🇪🇸 Valencia, Spain

Sanofi-Aventis Investigational Site Number 826005; 🇬🇧 Southampton, United Kingdom

Sanofi-Aventis Investigational Site Number 826001; 🇬🇧 Leicester, United Kingdom

Sanofi-Aventis Investigational Site Number 826002; 🇬🇧 Manchester, United Kingdom

Sanofi-Aventis Investigational Site Number 826003; 🇬🇧 Slough, United Kingdom