Study of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer (AFFIRM)
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Colorectal Neoplasms Neoplasm Metastasis |
Drug: aflibercept Drug: oxaliplatin Drug: 5-FU Drug: Folinic Acid |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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 |
- Progression Free Survival (PFS) Rate at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]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.
- 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) ] [ Designated as safety issue: No ]
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.
- 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) ] [ Designated as safety issue: No ]
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) [ Time Frame: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months) ] [ Designated as safety issue: No ]
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).
- 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 ] [ Designated as safety issue: Yes ]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 [ Time Frame: Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status ] [ Designated as safety issue: No ]The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.
| Enrollment: | 268 |
| Study Start Date: | February 2009 |
| Study Completion Date: | January 2012 |
| Primary Completion Date: | April 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
Drug: oxaliplatin
administration: IV infusion
Drug: 5-FU
administration: IV infusion
Drug: Folinic Acid
administration: IV infusion
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00851084
Show 37 Study Locations
| Principal Investigator: | John Zalcberg, MD | Peter Mc Callum Cancer Centre, Melbourne, Australia |
More Information
No publications provided
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT00851084 History of Changes |
| Other Study ID Numbers: | EFC10668, EudraCT 2008-004178-41 |
| Study First Received: | February 24, 2009 |
| Results First Received: | February 19, 2013 |
| Last Updated: | June 21, 2013 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Sanofi:
|
Angiogenesis Colon cancer Rectal cancer Oxaliplatin |
Additional relevant MeSH terms:
|
Colorectal Neoplasms Neoplasm Metastasis Neoplasms Colonic Diseases Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases |
Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms by Site Neoplastic Processes Pathologic Processes Rectal Diseases |
ClinicalTrials.gov processed this record on February 27, 2015