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

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

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 Overview

• Status: Completed
• Conditions: Neoplasm Metastasis; Colorectal Neoplasms
• Intervention / Treatment: Drug: oxaliplatin; Drug: 5-FU; Drug: Folinic Acid; Drug: aflibercept

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Douglas, Australia, 4814
    • Sanofi-Aventis Investigational Site Number 036004
  • Hunter Region Mail Centre, Australia, 2310
    • Sanofi-Aventis Investigational Site Number 036001
  • Hunter Region Mail Centre, Australia, 2310
    • Sanofi-Aventis Investigational Site Number 036003
• Germany
  • Berlin, Germany, 13353
    • Sanofi-Aventis Investigational Site Number 276003
  • Dresden, Germany, 01307
    • Sanofi-Aventis Investigational Site Number 276007
  • Hannover, Germany, 30625
    • Sanofi-Aventis Investigational Site Number 276001
  • Homberg, Germany, 66421
    • Sanofi-Aventis Investigational Site Number 276006
  • Mannheim, Germany, 68167
    • Sanofi-Aventis Investigational Site Number 276004
  • Münster, Germany, 48149
    • Sanofi-Aventis Investigational Site Number 276002
  • Recklinghausen, Germany, 45659
    • Sanofi-Aventis Investigational Site Number 276005
• Italy
  • Bari, Italy, 70126
    • Sanofi-Aventis Investigational Site Number 380005
  • Firenze, Italy, 50141
    • Sanofi-Aventis Investigational Site Number 380001
  • Milano, Italy, 20121
    • Sanofi-Aventis Investigational Site Number 380002
  • Taormina, Italy, 98039
    • Sanofi-Aventis Investigational Site Number 380003
  • Torino, Italy, 10126
    • Sanofi-Aventis Investigational Site Number 380004
• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
    • Sanofi-Aventis Investigational Site Number 410003
  • Cheongju, Korea, Republic of, 361-711
    • Sanofi-Aventis Investigational Site Number 410004
  • Daegu, Korea, Republic of, 700-721
    • Sanofi-Aventis Investigational Site Number 410005
  • Daejeon, Korea, Republic of
    • Sanofi-Aventis Investigational Site Number 410002
  • Goyang-Si, Gyeonggi-Do, Korea, Republic of, 410-769
    • Sanofi-Aventis Investigational Site Number 410007
  • Seoul, Korea, Republic of, 120-752
    • Sanofi-Aventis Investigational Site Number 410006
  • Seoul, Korea, Republic of, 152-703
    • Sanofi-Aventis Investigational Site Number 410001
  • Ulsan, Korea, Republic of, 682-714
    • Sanofi-Aventis Investigational Site Number 410008
• Russian Federation
  • Pyatigorsk, Russian Federation, 357500
    • Sanofi-Aventis Investigational Site Number 643002
  • Saint-Petersburg, Russian Federation, 197758
    • Sanofi-Aventis Investigational Site Number 643005
  • Sochi, Russian Federation, 354057
    • Sanofi-Aventis Investigational Site Number 643001
• Spain
  • Barcelona, Spain, 08036
    • Sanofi-Aventis Investigational Site Number 724005
  • Madrid, Spain, 28007
    • Sanofi-Aventis Investigational Site Number 724004
  • Madrid, Spain, 28040
    • Sanofi-Aventis Investigational Site Number 724001
  • Sabadell, Spain, 08208
    • Sanofi-Aventis Investigational Site Number 724002
  • Santiago De Compostela, Spain, 15706
    • Sanofi-Aventis Investigational Site Number 724007
  • Valencia, Spain, 46009
    • Sanofi-Aventis Investigational Site Number 724003
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Sanofi-Aventis Investigational Site Number 826004
  • Leicester, United Kingdom, LE1 5WW
    • Sanofi-Aventis Investigational Site Number 826001
  • Manchester, United Kingdom, M20 4BX
    • Sanofi-Aventis Investigational Site Number 826002
  • Slough, United Kingdom, SL2 4HL
    • Sanofi-Aventis Investigational Site Number 826003
  • Southampton, United Kingdom, SO16 6YD
    • Sanofi-Aventis Investigational Site Number 826005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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: oxaliplatin; administration: IV infusion; Drug: 5-FU; administration: IV infusion; Drug: Folinic Acid; administration: IV infusion; Drug: aflibercept; administration: IV infusion; Other Names: AVE0005; ZALTRAP™

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Principal Investigator: John Zalcberg, MD, Peter Mc Callum Cancer Centre, Melbourne, Australia

Publications and helpful links

General Publications

• Folprecht G, Pericay C, Saunders MP, Thomas A, Lopez Lopez R, Roh JK, Chistyakov V, Hohler 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: February 24, 2009
• First Submitted That Met QC Criteria: February 24, 2009
• First Posted (ESTIMATE): February 25, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 7, 2016
• Last Update Submitted That Met QC Criteria: May 4, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Rectal cancer; Angiogenesis; Oxaliplatin; Colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Hematinics; Oxaliplatin; Leucovorin; Levoleucovorin; Folic Acid; Aflibercept
• Other Study ID Numbers: EFC10668; EudraCT 2008-004178-41