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: June 21, 2013
Last verified: May 2013
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Consent withdrawn                 0                 2  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  
Number of Participants  
[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 ]

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
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Time Frame No text entered.
Additional Description Of the total 235 patients included in the safety population, 116 patients received mFOLFOX6 and 119 patients received aflibercept+mFOLFOX6. One patient, randomly assigned to the mFOLFOX6 arm did not receive any study treatment and was therefore excluded from the safety analyses.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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

Other Adverse Events
    mFOLFOX6 Only     mFOLFOX6 + Aflibercept  
Total, other (not including serious) adverse events      
# participants affected / at risk     114/116     117/119  
Blood and lymphatic system disorders      
Neutropenia * 1    
# participants affected / at risk     64/116 (55.17%)     53/119 (44.54%)  
Thrombocytopenia * 1    
# participants affected / at risk     25/116 (21.55%)     14/119 (11.76%)  
Anaemia * 1    
# participants affected / at risk     11/116 (9.48%)     11/119 (9.24%)  
Leukopenia * 1    
# participants affected / at risk     10/116 (8.62%)     11/119 (9.24%)  
Febrile neutropenia * 1    
# participants affected / at risk     2/116 (1.72%)     6/119 (5.04%)  
Eye disorders      
Lacrimation increased * 1    
# participants affected / at risk     3/116 (2.59%)     6/119 (5.04%)  
Gastrointestinal disorders      
Nausea * 1    
# participants affected / at risk     62/116 (53.45%)     62/119 (52.10%)  
Diarrhoea * 1    
# participants affected / at risk     51/116 (43.97%)     69/119 (57.98%)  
Stomatitis * 1    
# participants affected / at risk     44/116 (37.93%)     60/119 (50.42%)  
Constipation * 1    
# participants affected / at risk     31/116 (26.72%)     37/119 (31.09%)  
Vomiting * 1    
# participants affected / at risk     28/116 (24.14%)     34/119 (28.57%)  
Abdominal pain * 1    
# participants affected / at risk     25/116 (21.55%)     21/119 (17.65%)  
Dyspepsia * 1    
# participants affected / at risk     12/116 (10.34%)     21/119 (17.65%)  
Abdominal pain upper * 1    
# participants affected / at risk     14/116 (12.07%)     8/119 (6.72%)  
Proctalgia * 1    
# participants affected / at risk     3/116 (2.59%)     6/119 (5.04%)  
Mouth ulceration * 1    
# participants affected / at risk     1/116 (0.86%)     6/119 (5.04%)  
General disorders      
Fatigue * 1    
# participants affected / at risk     30/116 (25.86%)     41/119 (34.45%)  
Asthenia * 1    
# participants affected / at risk     30/116 (25.86%)     24/119 (20.17%)  
Pyrexia * 1    
# participants affected / at risk     18/116 (15.52%)     15/119 (12.61%)  
Oedema peripheral * 1    
# participants affected / at risk     8/116 (6.90%)     13/119 (10.92%)  
Immune system disorders      
Drug hypersensitivity * 1    
# participants affected / at risk     6/116 (5.17%)     4/119 (3.36%)  
Infections and infestations      
Urinary tract infection * 1    
# participants affected / at risk     12/116 (10.34%)     12/119 (10.08%)  
Nasopharyngitis * 1    
# participants affected / at risk     8/116 (6.90%)     16/119 (13.45%)  
Upper respiratory tract infection * 1    
# participants affected / at risk     5/116 (4.31%)     6/119 (5.04%)  
Investigations      
Weight decreased * 1    
# participants affected / at risk     6/116 (5.17%)     15/119 (12.61%)  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     6/116 (5.17%)     3/119 (2.52%)  
Alanine aminotransferase increased * 1    
# participants affected / at risk     6/116 (5.17%)     2/119 (1.68%)  
Metabolism and nutrition disorders      
Decreased appetite * 1    
# participants affected / at risk     37/116 (31.90%)     41/119 (34.45%)  
Musculoskeletal and connective tissue disorders      
Back pain * 1    
# participants affected / at risk     11/116 (9.48%)     9/119 (7.56%)  
Musculoskeletal pain * 1    
# participants affected / at risk     2/116 (1.72%)     8/119 (6.72%)  
Arthralgia * 1    
# participants affected / at risk     6/116 (5.17%)     2/119 (1.68%)  
Nervous system disorders      
Peripheral sensory neuropathy * 1    
# participants affected / at risk     35/116 (30.17%)     23/119 (19.33%)  
Headache * 1    
# participants affected / at risk     9/116 (7.76%)     39/119 (32.77%)  
Neuropathy peripheral * 1    
# participants affected / at risk     24/116 (20.69%)     23/119 (19.33%)  
Paraesthesia * 1    
# participants affected / at risk     25/116 (21.55%)     18/119 (15.13%)  
Polyneuropathy * 1    
# participants affected / at risk     16/116 (13.79%)     16/119 (13.45%)  
Lethargy * 1    
# participants affected / at risk     13/116 (11.21%)     14/119 (11.76%)  
Dysgeusia * 1    
# participants affected / at risk     16/116 (13.79%)     11/119 (9.24%)  
Dizziness * 1    
# participants affected / at risk     11/116 (9.48%)     12/119 (10.08%)  
Dysaesthesia * 1    
# participants affected / at risk     7/116 (6.03%)     7/119 (5.88%)  
Neurotoxicity * 1    
# participants affected / at risk     6/116 (5.17%)     0/119 (0.00%)  
Psychiatric disorders      
Insomnia * 1    
# participants affected / at risk     3/116 (2.59%)     10/119 (8.40%)  
Depression * 1    
# participants affected / at risk     3/116 (2.59%)     7/119 (5.88%)  
Renal and urinary disorders      
Proteinuria * 1    
# participants affected / at risk     1/116 (0.86%)     28/119 (23.53%)  
Respiratory, thoracic and mediastinal disorders      
Epistaxis * 1    
# participants affected / at risk     15/116 (12.93%)     34/119 (28.57%)  
Dyspnoea * 1    
# participants affected / at risk     8/116 (6.90%)     22/119 (18.49%)  
Cough * 1    
# participants affected / at risk     14/116 (12.07%)     12/119 (10.08%)  
Dysphonia * 1    
# participants affected / at risk     3/116 (2.59%)     22/119 (18.49%)  
Oropharyngeal pain * 1    
# participants affected / at risk     3/116 (2.59%)     8/119 (6.72%)  
Rhinorrhoea * 1    
# participants affected / at risk     2/116 (1.72%)     6/119 (5.04%)  
Skin and subcutaneous tissue disorders      
Alopecia * 1    
# participants affected / at risk     15/116 (12.93%)     13/119 (10.92%)  
Palmar-plantar erythrodysaesthesia syndrome * 1    
# participants affected / at risk     6/116 (5.17%)     20/119 (16.81%)  
Rash * 1    
# participants affected / at risk     7/116 (6.03%)     6/119 (5.04%)  
Dry skin * 1    
# participants affected / at risk     6/116 (5.17%)     5/119 (4.20%)  
Pruritus * 1    
# participants affected / at risk     6/116 (5.17%)     5/119 (4.20%)  
Skin hyperpigmentation * 1    
# participants affected / at risk     6/116 (5.17%)     5/119 (4.20%)  
Vascular disorders      
Hypertension * 1    
# participants affected / at risk     8/116 (6.90%)     64/119 (53.78%)  
Deep vein thrombosis * 1    
# participants affected / at risk     2/116 (1.72%)     7/119 (5.88%)  
Phlebitis * 1    
# participants affected / at risk     0/116 (0.00%)     6/119 (5.04%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 13.1



  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.


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