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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Consent withdrawn                0                2 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 ]

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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