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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00851084




Registration number
NCT00851084
Ethics application status
Date submitted
24/02/2009
Date registered
24/02/2009
Date last updated
4/05/2016

Titles & IDs
Public title
Study of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer
Scientific title
Randomized, Multinational, Study Of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer
Secondary ID [1] 0 0
EudraCT 2008-004178-41
Secondary ID [2] 0 0
EFC10668
Universal Trial Number (UTN)
Trial acronym
AFFIRM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Neoplasm Metastasis 0 0
Colorectal Neoplasms 0 0
Neoplasm Metastasis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - aflibercept
Treatment: Drugs - oxaliplatin
Treatment: Drugs - 5-FU
Treatment: Drugs - Folinic Acid
Treatment: Drugs - aflibercept
Treatment: Drugs - oxaliplatin
Treatment: Drugs - 5-FU
Treatment: Drugs - Folinic Acid

Active Comparator: mFOLFOX6 only - modified FOLFOX6 chemotherapy regimen

Experimental: mFOLFOX6 + aflibercept - modified FOLFOX6 chemotherapy regimen in combination with aflibercept

Active Comparator: mFOLFOX6 only - modified FOLFOX6 chemotherapy regimen

Experimental: mFOLFOX6 + aflibercept - modified FOLFOX6 chemotherapy regimen in combination with aflibercept


Treatment: Drugs: aflibercept
administration: IV infusion

Treatment: Drugs: oxaliplatin
administration: IV infusion

Treatment: Drugs: 5-FU
administration: IV infusion

Treatment: Drugs: Folinic Acid
administration: IV infusion

Treatment: Drugs: aflibercept
administration: IV infusion

Treatment: Drugs: oxaliplatin
administration: IV infusion

Treatment: Drugs: 5-FU
administration: IV infusion

Treatment: Drugs: Folinic Acid
administration: IV infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
12 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Secondary outcome [3] 0 0
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).
Timepoint [3] 0 0
From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized
Secondary outcome [5] 0 0
Immunogenicity of Intravenous (IV) Aflibercept - The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.
Timepoint [5] 0 0
Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Secondary outcome [7] 0 0
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).
Timepoint [7] 0 0
From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Secondary outcome [8] 0 0
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).
Timepoint [8] 0 0
From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized
Secondary outcome [10] 0 0
Immunogenicity of Intravenous (IV) Aflibercept - The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.
Timepoint [10] 0 0
Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status

Eligibility
Key inclusion criteria
- Histologically proven adenocarcinoma of the colon or the rectum

- Metastatic disease not amenable to potentially curative treatment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Investigational Site Number 036004 - Douglas
Recruitment hospital [2] 0 0
Sanofi-Aventis Investigational Site Number 036001 - Hunter Region Mail Centre
Recruitment hospital [3] 0 0
Sanofi-Aventis Investigational Site Number 036003 - Hunter Region Mail Centre
Recruitment postcode(s) [1] 0 0
4814 - Douglas
Recruitment postcode(s) [2] 0 0
2310 - Hunter Region Mail Centre
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Berlin
Country [2] 0 0
Germany
State/province [2] 0 0
Dresden
Country [3] 0 0
Germany
State/province [3] 0 0
Hannover
Country [4] 0 0
Germany
State/province [4] 0 0
Homberg
Country [5] 0 0
Germany
State/province [5] 0 0
Mannheim
Country [6] 0 0
Germany
State/province [6] 0 0
Münster
Country [7] 0 0
Germany
State/province [7] 0 0
Recklinghausen
Country [8] 0 0
Italy
State/province [8] 0 0
Bari
Country [9] 0 0
Italy
State/province [9] 0 0
Firenze
Country [10] 0 0
Italy
State/province [10] 0 0
Milano
Country [11] 0 0
Italy
State/province [11] 0 0
Taormina
Country [12] 0 0
Italy
State/province [12] 0 0
Torino
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Busan
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Cheongju
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Daegu
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Daejeon
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Goyang-Si, Gyeonggi-Do
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Ulsan
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Pyatigorsk
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Saint-Petersburg
Country [22] 0 0
Russian Federation
State/province [22] 0 0
Sochi
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Sabadell
Country [26] 0 0
Spain
State/province [26] 0 0
Santiago De Compostela
Country [27] 0 0
Spain
State/province [27] 0 0
Valencia
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Leeds
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Leicester
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Manchester
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Slough
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00851084
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Zalcberg, MD
Address 0 0
Peter Mc Callum Cancer Centre, Melbourne, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications