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

Colorectal Neoplasms Clinical Trial

— AFFIRM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00851084
• Other study ID #: EFC10668
• Secondary ID: EudraCT 2008-004
• Status: Completed
• Phase: Phase 2
• First received: February 24, 2009
• Last updated: June 21, 2013
• Start date: February 2009
• Est. completion date: January 2012

Study information

• Verified date: May 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 268
• Est. completion date: January 2012
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoplasm Metastasis
• Neoplasms

Intervention

Drug:
• aflibercept
administration: IV infusion
• oxaliplatin
administration: IV infusion
• 5-FU
administration: IV infusion
• Folinic Acid
administration: IV infusion

Locations

Country	Name	City	State
Australia	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
Germany	Sanofi-Aventis Investigational Site Number 276003	Berlin
Germany	Sanofi-Aventis Investigational Site Number 276007	Dresden
Germany	Sanofi-Aventis Investigational Site Number 276001	Hannover
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
Italy	Sanofi-Aventis Investigational Site Number 380005	Bari
Italy	Sanofi-Aventis Investigational Site Number 380001	Firenze
Italy	Sanofi-Aventis Investigational Site Number 380002	Milano
Italy	Sanofi-Aventis Investigational Site Number 380003	Taormina
Italy	Sanofi-Aventis Investigational Site Number 380004	Torino
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410003	Busan
Korea, Republic of	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 410002	Daejeon
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410007	Goyang-Si, Gyeonggi-Do
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410001	Seoul
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410006	Seoul
Korea, Republic of	Sanofi-Aventis Investigational Site Number 410008	Ulsan
Russian Federation	Sanofi-Aventis Investigational Site Number 643002	Pyatigorsk
Russian Federation	Sanofi-Aventis Investigational Site Number 643005	Saint-Petersburg
Russian Federation	Sanofi-Aventis Investigational Site Number 643001	Sochi
Spain	Sanofi-Aventis Investigational Site Number 724005	Barcelona
Spain	Sanofi-Aventis Investigational Site Number 724001	Madrid
Spain	Sanofi-Aventis Investigational Site Number 724004	Madrid
Spain	Sanofi-Aventis Investigational Site Number 724002	Sabadell
Spain	Sanofi-Aventis Investigational Site Number 724007	Santiago De Compostela
Spain	Sanofi-Aventis Investigational Site Number 724003	Valencia
United Kingdom	Sanofi-Aventis Investigational Site Number 826004	Leeds
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	Sanofi-Aventis Investigational Site Number 826005	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Australia,  Germany,  Italy,  Korea, Republic of,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	Yes
Secondary	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	No