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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00851084
First received: February 24, 2009
Last updated: May 4, 2016
Last verified: May 2016
Results First Received: February 19, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Colorectal Neoplasms
Neoplasm Metastasis
Interventions: Drug: aflibercept
Drug: oxaliplatin
Drug: 5-FU
Drug: Folinic Acid

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
There were 268 patients screened (informed consent signed) for this study. Of these screened patients, 236 patients were subsequently randomly assigned to treatments. 32 patients were screen failures.

Reporting Groups
  Description
mFOLFOX6 Only modified FOLFOX6
mFOLFOX6 + Aflibercept modified FOLFOX6 in combination with aflibercept

Participant Flow:   Overall Study
    mFOLFOX6 Only   mFOLFOX6 + Aflibercept
STARTED   117   119 
COMPLETED   0 [1]   0 [1] 
NOT COMPLETED   117   119 
Randomized but not treated                1                0 
Adverse Event                26                36 
Disease progression                52                47 
Poor compliance to protocol                1                1 
Physician Decision                13                14 
Consent withdrawn                0                2 
Withdrawal by Subject                11                12 
Metastatic surgery                6                6 
Not specified                7                1 
[1] Participants continued treatment until they met treatment discontinuation criteria.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
mFOLFOX6 Only modified FOLFOX6
mFOLFOX6 + Aflibercept modified FOLFOX6 in combination with aflibercept
Total Total of all reporting groups

Baseline Measures
   mFOLFOX6 Only   mFOLFOX6 + Aflibercept   Total 
Overall Participants Analyzed 
[Units: Participants]
 117   119   236 
Age 
[Units: Years]
Mean (Standard Deviation)
 62.4  (9.7)   61.8  (9.0)   62.1  (9.4) 
Age, Customized 
[Units: Participants]
     
<65   65   70   135 
>=65 but <75   43   45   88 
>=75   9   4   13 
Gender 
[Units: Participants]
     
Female   49   43   92 
Male   68   76   144 
Race/Ethnicity, Customized 
[Units: Participants]
     
Caucasian/White   90   97   187 
Black   0   1   1 
Asian/Oriental   27   20   47 
Other   0   1   1 
Region of Enrollment 
[Units: Participants]
     
United Kingdom   22   28   50 
Korea, Republic of   26   20   46 
Germany   18   24   42 
Spain   24   18   42 
Russian Federation   15   15   30 
Italy   10   5   15 
Australia   2   9   11 
Body Surface Are (BSA) 
[Units: M^2]
Mean (Standard Deviation)
 1.8  (0.2)   1.8  (0.2)   1.8  (0.2) 


  Outcome Measures
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1.  Primary:   Progression Free Survival (PFS) Rate at 12 Months   [ Time Frame: 12 months ]

2.  Secondary:   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) ]

3.  Secondary:   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) ]

4.  Secondary:   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) ]

5.  Secondary:   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 ]
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Measure Type Secondary
Measure Title Number of Participants With Treatment-emergent Adverse Events (TEAE)
Measure Description 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.
Time Frame From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Of the total 235 patients included in the safety population, 116 patients received mFOLFOX6 and 119 patients received mFOLFOX6 + aflibercept. One patient, randomly assigned to the mFOLFOX6 arm did not receive any study treatment and was therefore excluded from the safety analyses.

Reporting Groups
  Description
mFOLFOX6 Only modified FOLFOX6
mFOLFOX6 + Aflibercept modified FOLFOX6 in combination with aflibercept

Measured Values
   mFOLFOX6 Only   mFOLFOX6 + Aflibercept 
Participants Analyzed 
[Units: Participants]
 116   119 
Number of Participants With Treatment-emergent Adverse Events (TEAE) 
[Units: Participants]
   
Treatment Emergent Adverse Event (TEAE)   115   119 
Grade 3-4 TEAE   87   108 
Treatment emergent Serious Adverse Event (SAE)   32   55 
TEAE leading to death   2   8 
Premature treatment discontinuation   NA [1]   34 
Permanent treatment discontinuation   26   37 
[1] Analysis was limited to mFOLFOX6 + aflibercept arm.

No statistical analysis provided for Number of Participants With Treatment-emergent Adverse Events (TEAE)



6.  Secondary:   Immunogenicity of Intravenous (IV) Aflibercept   [ Time Frame: Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The overall survival (OS) data are severely limited due to the low number of events (<50%) in both arms, therefore median OS cannot be accurately estimated due to limitations of available data.


  More Information