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Consent withdrawn                 0                 2  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
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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.

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

Serious Adverse Events
    mFOLFOX6 Only     mFOLFOX6 + Aflibercept  
Total, serious adverse events      
# participants affected / at risk     32/116 (27.59%)     55/119 (46.22%)  
Blood and lymphatic system disorders      
Neutropenia * 1    
# participants affected / at risk     1/116 (0.86%)     3/119 (2.52%)  
Febrile neutropenia * 1    
# participants affected / at risk     2/116 (1.72%)     2/119 (1.68%)  
Cardiac disorders      
Sinoatrial block * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Ventricular arrhythmia * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Endocrine disorders      
Adrenal insufficiency * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Eye disorders      
Vision blurred * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Retinal detachment * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Gastrointestinal disorders      
Nausea * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Diarrhoea * 1    
# participants affected / at risk     3/116 (2.59%)     3/119 (2.52%)  
Stomatitis * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Constipation * 1    
# participants affected / at risk     0/116 (0.00%)     2/119 (1.68%)  
Vomiting * 1    
# participants affected / at risk     2/116 (1.72%)     3/119 (2.52%)  
Abdominal pain * 1    
# participants affected / at risk     2/116 (1.72%)     2/119 (1.68%)  
Rectal haemorrhage * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Intestinal obstruction * 1    
# participants affected / at risk     4/116 (3.45%)     2/119 (1.68%)  
Dysphagia * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Haematochezia * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Ascites * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Colonic obstruction * 1    
# participants affected / at risk     3/116 (2.59%)     0/119 (0.00%)  
Melaena * 1    
# participants affected / at risk     1/116 (0.86%)     1/119 (0.84%)  
Anal fistula * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Ileal perforation * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Large intestine perforation * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Mechanical ileus * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Small intestinal obstruction * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Subileus * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
General disorders      
Fatigue * 1    
# participants affected / at risk     1/116 (0.86%)     2/119 (1.68%)  
Pyrexia * 1    
# participants affected / at risk     3/116 (2.59%)     6/119 (5.04%)  
Disease progression * 1    
# participants affected / at risk     1/116 (0.86%)     4/119 (3.36%)  
Medical device complication * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
General physical health deterioration * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Hepatobiliary disorders      
Hyperbilirubinaemia * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Bile duct obstruction * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Immune system disorders      
Drug hypersensitivity * 1    
# participants affected / at risk     0/116 (0.00%)     3/119 (2.52%)  
Infections and infestations      
Urinary tract infection * 1    
# participants affected / at risk     0/116 (0.00%)     2/119 (1.68%)  
Catheter site infection * 1    
# participants affected / at risk     3/116 (2.59%)     3/119 (2.52%)  
Pneumonia * 1    
# participants affected / at risk     1/116 (0.86%)     4/119 (3.36%)  
Cystitis * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Device related infection * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Infection * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Neutropenic infection * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Abdominal infection * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Gastroenteritis norovirus * 1    
# participants affected / at risk     0/116 (0.00%)     2/119 (1.68%)  
Infectious peritonitis * 1    
# participants affected / at risk     0/116 (0.00%)     2/119 (1.68%)  
Lower respiratory tract infection * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Neutropenic sepsis * 1    
# participants affected / at risk     1/116 (0.86%)     1/119 (0.84%)  
Bacterial infection * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Bronchopneumonia * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Folliculitis * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Fungaemia * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Gastroenteritis * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Pneumonia viral * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Pyelonephritis * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Sepsis * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Septic shock * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Staphylococcal sepsis * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Subcutaneous abscess * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Urosepsis * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Injury, poisoning and procedural complications      
Anastomotic leak * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Head injury * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Postoperative wound complication * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Investigations      
Neutrophil count decreased * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Metabolism and nutrition disorders      
Dehydration * 1    
# participants affected / at risk     1/116 (0.86%)     1/119 (0.84%)  
Malnutrition * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Musculoskeletal and connective tissue disorders      
Pathological fracture * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Neoplasm progression * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Nervous system disorders      
Peripheral sensory neuropathy * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Lethargy * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Presyncope * 1    
# participants affected / at risk     1/116 (0.86%)     1/119 (0.84%)  
Convulsion * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Haemorrhage intracranial * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Ischaemic stroke * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Posterior reversible encephalopathy syndrome * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Renal and urinary disorders      
Proteinuria * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Haematuria * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Urinary retention * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Renal failure * 1    
# participants affected / at risk     0/116 (0.00%)     2/119 (1.68%)  
Respiratory, thoracic and mediastinal disorders      
Epistaxis * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Dyspnoea * 1    
# participants affected / at risk     0/116 (0.00%)     2/119 (1.68%)  
Pulmonary embolism * 1    
# participants affected / at risk     3/116 (2.59%)     4/119 (3.36%)  
Acute respiratory distress syndrome * 1    
# participants affected / at risk     0/116 (0.00%)     2/119 (1.68%)  
Skin and subcutaneous tissue disorders      
Pyoderma gangrenosum * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Social circumstances      
Social stay hospitalisation * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Surgical and medical procedures      
Malignant tumour excision * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Tumour excision * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Vascular disorders      
Subclavian vein thrombosis * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Circulatory collapse * 1    
# participants affected / at risk     1/116 (0.86%)     0/119 (0.00%)  
Hypertensive crisis * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
Lymphatic fistula * 1    
# participants affected / at risk     0/116 (0.00%)     1/119 (0.84%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 13.1




  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.


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