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

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Neoplasms; Neoplasm Metastasis	Drug: aflibercept; Drug: oxaliplatin; Drug: 5-FU; Drug: Folinic Acid	Phase 2

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	268 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized, Multinational, Study Of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer
Study Start Date :	February 2009
Actual Primary Completion Date :	April 2011
Actual Study Completion Date :	January 2012

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: mFOLFOX6 only; modified FOLFOX6 chemotherapy regimen	Drug: oxaliplatin; administration: IV infusion Drug: 5-FU; administration: IV infusion Drug: Folinic Acid; administration: IV infusion
Experimental: mFOLFOX6 + aflibercept; modified FOLFOX6 chemotherapy regimen in combination with aflibercept	Drug: aflibercept; administration: IV infusion; Other Names: ZALTRAP™; AVE0005 Drug: oxaliplatin; administration: IV infusion Drug: 5-FU; administration: IV infusion Drug: Folinic Acid; administration: IV infusion

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Progression Free Survival (PFS) Rate at 12 Months [ Time Frame: 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 :

1. Progression Free Survival (PFS) [ Time Frame: 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.

2. Overall Objective Response Rate (ORR) [ Time Frame: 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).

3. Overall Survival (OS) [ Time Frame: 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).

4. Number of Participants With Treatment-emergent Adverse Events (TEAE) [ Time Frame: 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.
5. Immunogenicity of Intravenous (IV) Aflibercept [ Time Frame: 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.

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 37 Study Locations

Sponsors and Collaborators

Sanofi

Investigators

Principal Investigator:	John Zalcberg, MD	Peter Mc Callum Cancer Centre, Melbourne, Australia

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Folprecht G, Pericay C, Saunders MP, Thomas A, Lopez Lopez R, Roh JK, Chistyakov V, Höhler T, Kim JS, Hofheinz RD, Ackland SP, Swinson D, Kopp M, Udovitsa D, Hall M, Iveson T, Vogel A, Zalcberg JR. Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study. Ann Oncol. 2016 Jul;27(7):1273-9. doi: 10.1093/annonc/mdw176. Epub 2016 Apr 18.

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT00851084 History of Changes
Other Study ID Numbers:	EFC10668; EudraCT 2008-004178-41
First Posted:	February 25, 2009
Results First Posted:	June 25, 2013
Last Update Posted:	June 7, 2016
Last Verified:	May 2016

Keywords provided by Sanofi:

Angiogenesis; Colon cancer; Rectal cancer; Oxaliplatin

Additional relevant MeSH terms:

Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes	Oxaliplatin; Leucovorin; Levoleucovorin; Folic Acid; Antineoplastic Agents; Antidotes; Protective Agents; Physiological Effects of Drugs; Vitamin B Complex; Vitamins; Micronutrients; Growth Substances; Hematinics