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Trial record 52 of 78 for:    sanofi-aventis and sweden

Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen (VELOUR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00561470
Recruitment Status : Completed
First Posted : November 21, 2007
Results First Posted : September 28, 2012
Last Update Posted : September 28, 2012
Sponsor:
Collaborators:
Regeneron Pharmaceuticals
NSABP Foundation Inc
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Colorectal Neoplasms
Neoplasm Metastasis
Interventions Drug: Placebo
Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Drug: FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Enrollment 1226
Recruitment Details Between 19 November 2007 and 16 March 2010, 614 participants were randomized to the placebo arm and 612 participants were randomized to the aflibercept arm.
Pre-assignment Details  
Arm/Group Title Placebo/FOLFIRI Aflibercept/FOLFIRI
Hide Arm/Group Description Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept, followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Period Title: Overall Study
Started 614 612
TREATED 609 607
SAFETY POPULATION 605 [1] 611 [2]
ONGOING TREATMENT 11 [3] 14 [3]
Completed 0 [4] 0 [4]
Not Completed 614 612
Reason Not Completed
Adverse Event             74             163
Disease progression             437             305
poor compliance to protocol             4             4
Lost to Follow-up             2             0
Physician Decision             21             20
Consent Withdrawn             2             6
Subject request             43             77
Metastatic surgery             10             12
Unauthorized procedure             3             1
Randomized but not treated             5             5
Missed visit window             1             4
Planning surgery             1             1
Ongoing Treatment             11             14
[1]
Treated participants excluding 4 who received at least 1 dose of Aflibercept
[2]
Treated participants including 4 from Placebo/FOLFIRI who received at least 1 dose of Aflibercept
[3]
Participants continuing treatment on the cutoff date of the final analysis
[4]
Participants met treatment discontinuation criteria or were ongoing treatment on the cutoff date
Arm/Group Title Placebo/Folfiri Aflibercept/Folfiri Total
Hide Arm/Group Description Participants with Metastatic Colorectal Cancer administered Placebo and FOLFIRI (Irinotecan, 5- Fluorouracil, and Leucovorin) Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept and FOLFIRI (Irinotecan, 5- Fluorouracil, and Leucovorin) Total of all reporting groups
Overall Number of Baseline Participants 614 612 1226
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 614 participants 612 participants 1226 participants
60.2  (10.8) 59.5  (10.5) 59.8  (10.7)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 612 participants 1226 participants
<65 years 376 407 783
>=65 but <75 years 199 172 371
>=75 years 39 33 72
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 612 participants 1226 participants
Male 353 365 718
Female 261 247 508
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 612 participants 1226 participants
Caucasian/White 523 548 1071
Black 27 16 43
Asian/Oriental 51 35 86
Other 13 13 26
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 612 participants 1226 participants
ARGENTINA 4 2 6
AUSTRALIA 42 54 96
AUSTRIA 3 4 7
BELGIUM 37 45 82
BRAZIL 21 27 48
CHILE 31 33 64
CZECH REPUBLIC 30 47 77
DENMARK 9 6 15
ESTONIA 7 3 10
FRANCE 1 1 2
GERMANY 23 12 35
GREECE 9 10 19
ITALY 26 23 49
KOREA, REPUBLIC OF 39 26 65
NETHERLANDS 20 14 34
NEW ZEALAND 13 7 20
NORWAY 14 19 33
POLAND 24 32 56
PUERTO RICO 4 2 6
ROMANIA 16 16 32
RUSSIAN FEDERATION 35 40 75
SOUTH AFRICA 36 31 67
SPAIN 27 28 55
SWEDEN 10 4 14
TURKEY 4 2 6
UKRAINE 11 11 22
UNITED KINGDOM 47 52 99
UNITED STATES 71 61 132
Eastern Cooperative Oncology Group (ECOG) performance status score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 612 participants 1226 participants
Participants with ECOG Score = 0 350 349 699
Participants with ECOG Score = 1 250 250 500
Participants with ECOG Score = 2 14 13 27
[1]
Measure Description: The ECOG score assesses how the disease affects a participant's daily living abilities. It ranges from 0-5, with 0 being the best and 5 being the worst outcome. "0" reflects a fully active participant, able to carry on all pre-disease performance without restriction. "1" reflects a participant restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. "2" reflects an ambulatory participant, who is up and about more than 50% of waking hours, and capable of all self-care but unable to carry out any work activities.
Prior Bevacizumab   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 612 participants 1226 participants
Yes 187 186 373
No 427 426 853
[1]
Measure Description: Number of participants randomized in the prior bevacizumab stratum as per the interactive voice response system (IVRS).
1.Primary Outcome
Title Overall Survival (OS)
Hide Description

Overall Survival was the time interval from the date of randomization to the date of death due to any cause. Once disease progression was documented, participants were followed every 2 months for survival status, until death or until the study cutoff date, whichever came first. The final data cutoff date for the analysis of OS was the date when 863 deaths had occurred (07 February 2011).

OS was estimated using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model.

Time Frame From the date of the first randomization until the study data cut-off date, 07 February 2011 (approximately three years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population (ITT) – all participants who gave informed consent and were randomized.
Arm/Group Title Placebo/FOLFIRI Aflibercept/FOLFIRI
Hide Arm/Group Description:
Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept, followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Overall Number of Participants Analyzed 614 612
Overall Number of Units Analyzed
Type of Units Analyzed: Events (Death)
460 403
Median (Inter-Quartile Range)
Unit of Measure: months
12.06
(6.83 to 21.03)
13.50
(7.62 to 25.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/FOLFIRI, Aflibercept/FOLFIRI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments Stratified Log-Rank test p-value. Stratified on ECOG Performance Status and prior Bevacizumab according to IVRS using the Cox Proportional Hazard Model. Significance threshold was set to 0.0466 using the O'Brien-Fleming alpha spending function.
Method Stratified Log-Rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Hazard Ratio
Estimated Value 0.817
Confidence Interval (2-Sided) 95.34%
0.713 to 0.937
Estimation Comments Stratified on ECOG Performance Status (0 vs 1 vs 2) and prior Bevacizumab (yes vs no) according to IVRS using the Cox Proportional Hazard Model. Significance threshold was set to 0.0466 using the O'Brien-Fleming alpha spending function.
2.Secondary Outcome
Title Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)
Hide Description

PFS was the time interval from the date of randomization to the date of progression, or death from any cause if it occurs before tumor progression is documented. To evaluate disease progression, copies of all tumor imaging sets were systematically collected and assessed by the IRC.

PFS was analyzed using the Kaplan-Meier method, and the Hazard Ratio was estimated using the Cox Proportional Hazard Model.

The analysis for PFS was performed as planned when 561 deaths (OS events) had occurred.

Time Frame From the date of the first randomization until the occurrence of 561 OS events, 06 May 2010 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population included all participants who gave informed consent and were randomized.
Arm/Group Title Placebo/FOLFIRI Aflibercept/FOLFIRI
Hide Arm/Group Description:
Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept, followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Overall Number of Participants Analyzed 614 612
Overall Number of Units Analyzed
Type of Units Analyzed: First PFS Events
454 393
Median (Inter-Quartile Range)
Unit of Measure: months
4.67
(2.60 to 9.10)
6.90
(3.84 to 10.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/FOLFIRI, Aflibercept/FOLFIRI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00007
Comments Stratified on ECOG Performance Status (0 vs 1 vs 2) and prior Bevacizumab (yes vs no) according to IVRS
Method Stratified Log-Rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Hazard ratio
Estimated Value 0.758
Confidence Interval (2-Sided) 99.99%
0.578 to 0.995
Estimation Comments Stratified on ECOG Performance Status (0 vs 1 vs 2) and prior Bevacizumab (yes vs no) according to IVRS using the Cox Proportional Hazard Model.
3.Secondary Outcome
Title Overall Objective Response Rate (ORR) Based on the Tumor Assessment by the Independent Review Committee (IRC) as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria
Hide Description

The overall ORR was the percentage of evaluable participants who achieved complete response [CR] or partial response [PR] according to RECIST criteria version 1.0.

  • CR reflected the disappearance of all tumor lesions (with no new tumors)
  • PR reflected a pre-defined reduction in tumor burden

Tumors were assessed by the IRC using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 – 6 weeks.

Time Frame From the date of the first randomization until the study data cut-off date, 06 May 2010 (approximately 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The evaluable patient population (EPP) for tumor response included all randomized participants with measurable disease at study entry, as per IRC evaluation, and with at least one valid post-baseline tumor evaluation.
Arm/Group Title Placebo/FOLFIRI Aflibercept/FOLFIRI
Hide Arm/Group Description:
Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept, followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Overall Number of Participants Analyzed 530 531
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
11.1
(8.5 to 13.8)
19.8
(16.4 to 23.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/FOLFIRI, Aflibercept/FOLFIRI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Stratified Cochran-Mantel-Haenszel
Comments Stratified on ECOG Performance Status (0 vs 1 vs 2) and Prior Bevacizumab (yes vs no) according to IVRS.
4.Secondary Outcome
Title Number of Participants With Adverse Events (AE)
Hide Description

All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 30 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization.

The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.

Time Frame From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was the subset of the ITT population that took at least one dose of study treatment. Analyses was based on the treatment actually received (any participant who received at least one dose of aflibercept, even when receiving the rest of study treatment with placebo, was counted in the aflibercept treatment arm).
Arm/Group Title Placebo/FOLFIRI Aflibercept/FOLFIRI
Hide Arm/Group Description:
Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept, followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
Overall Number of Participants Analyzed 605 611
Measure Type: Number
Unit of Measure: participants
Treatment-Emergent Adverse Event (TEAE) 592 606
Serious TEAE 198 294
TEAE leading to Death 29 37
TEAE causing permanent treatment discontinuation 73 164
5.Secondary Outcome
Title Immunogenicity Assessment: Number of Participants With Positive Sample(s) in the Anti-drug Antibodies (ADA) Assay and in the Neutralizing Anti-drug Antibodies (NAb) Assay
Hide Description Serum samples for immunogenicity assessment were analyzed using a bridging immunoassay to detect ADA. Positive samples in the ADA assay were further analyzed in the NAb assay using a validated, non-quantitative ligand binding assay.
Time Frame Baseline, every other treatment cycle, 30 days and 90 days after the last infusion of aflibercept/placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Immunogenicity population included all participants who were treated and tested for immunogenicity at least once post-baseline.
Arm/Group Title Placebo/FOLFIRI Aflibercept/FOLFIRI
Hide Arm/Group Description:
Participants with Metastatic Colorectal Cancer administered Placebo and FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Participants with Metastatic Colorectal Cancer administered Aflibercept and FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
Overall Number of Participants Analyzed 526 521
Measure Type: Number
Unit of Measure: participants
At least one positive sample in the ADA assay 18 8
At least one positive sample in the NAb assay 2 1
Time Frame From treatment initiation to 7 February, 2011
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo/FOLFIRI Aflibercept/FOLFIRI
Hide Arm/Group Description Participants with Metastatic Colorectal Cancer administered Placebo followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks Participants with Metastatic Colorectal Cancer administered 4 mg/kg of Aflibercept, followed by FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) every two weeks
All-Cause Mortality
Placebo/FOLFIRI Aflibercept/FOLFIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo/FOLFIRI Aflibercept/FOLFIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   198/605 (32.73%)   294/611 (48.12%) 
Blood and lymphatic system disorders     
Neutropenia * 1  4/605 (0.66%)  11/611 (1.80%) 
Thrombocytopenia * 1  3/605 (0.50%)  2/611 (0.33%) 
Anaemia * 1  3/605 (0.50%)  7/611 (1.15%) 
Febrile neutropenia * 1  6/605 (0.99%)  19/611 (3.11%) 
Coagulopathy * 1  0/605 (0.00%)  2/611 (0.33%) 
Pancytopenia * 1  0/605 (0.00%)  2/611 (0.33%) 
Thrombotic microangiopathy * 1  0/605 (0.00%)  1/611 (0.16%) 
Cardiac disorders     
Angina pectoris * 1  0/605 (0.00%)  1/611 (0.16%) 
Atrial fibrillation * 1  2/605 (0.33%)  3/611 (0.49%) 
Sinus bradycardia * 1  0/605 (0.00%)  1/611 (0.16%) 
Acute myocardial infarction * 1  0/605 (0.00%)  2/611 (0.33%) 
Myocardial ischaemia * 1  1/605 (0.17%)  0/611 (0.00%) 
Cardiac failure congestive * 1  0/605 (0.00%)  1/611 (0.16%) 
Intracardiac thrombus * 1  0/605 (0.00%)  1/611 (0.16%) 
Myocardial infarction * 1  0/605 (0.00%)  1/611 (0.16%) 
Pericarditis * 1  1/605 (0.17%)  0/611 (0.00%) 
Endocrine disorders     
Hypercalcaemia of malignancy * 1  1/605 (0.17%)  0/611 (0.00%) 
Eye disorders     
Periorbital oedema * 1  0/605 (0.00%)  1/611 (0.16%) 
Gastrointestinal disorders     
Diarrhoea * 1  14/605 (2.31%)  44/611 (7.20%) 
Nausea * 1  3/605 (0.50%)  4/611 (0.65%) 
Stomatitis * 1  0/605 (0.00%)  8/611 (1.31%) 
Vomiting * 1  7/605 (1.16%)  10/611 (1.64%) 
Abdominal pain * 1  7/605 (1.16%)  12/611 (1.96%) 
Constipation * 1  4/605 (0.66%)  6/611 (0.98%) 
Abdominal pain upper * 1  3/605 (0.50%)  4/611 (0.65%) 
Haemorrhoids * 1  0/605 (0.00%)  2/611 (0.33%) 
Rectal haemorrhage * 1  4/605 (0.66%)  6/611 (0.98%) 
Aphthous stomatitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Proctalgia * 1  0/605 (0.00%)  3/611 (0.49%) 
Ascites * 1  4/605 (0.66%)  3/611 (0.49%) 
Gastrooesophageal reflux disease * 1  0/605 (0.00%)  1/611 (0.16%) 
Intestinal obstruction * 1  11/605 (1.82%)  10/611 (1.64%) 
Abdominal pain lower * 1  1/605 (0.17%)  1/611 (0.16%) 
Gastritis * 1  0/605 (0.00%)  1/611 (0.16%) 
Enteritis * 1  1/605 (0.17%)  2/611 (0.33%) 
Gingivitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Ileus * 1  5/605 (0.83%)  4/611 (0.65%) 
Colitis * 1  1/605 (0.17%)  4/611 (0.65%) 
Small intestinal obstruction * 1  2/605 (0.33%)  5/611 (0.82%) 
Anal haemorrhage * 1  1/605 (0.17%)  0/611 (0.00%) 
Faecal incontinence * 1  1/605 (0.17%)  0/611 (0.00%) 
Gastrointestinal haemorrhage * 1  0/605 (0.00%)  3/611 (0.49%) 
Gastrointestinal inflammation * 1  0/605 (0.00%)  3/611 (0.49%) 
Periodontitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Gastrointestinal obstruction * 1  2/605 (0.33%)  1/611 (0.16%) 
Haematemesis * 1  2/605 (0.33%)  0/611 (0.00%) 
Mechanical ileus * 1  2/605 (0.33%)  1/611 (0.16%) 
Colitis ischaemic * 1  0/605 (0.00%)  1/611 (0.16%) 
Colonic obstruction * 1  0/605 (0.00%)  2/611 (0.33%) 
Duodenal ulcer perforation * 1  1/605 (0.17%)  1/611 (0.16%) 
Peritonitis * 1  1/605 (0.17%)  1/611 (0.16%) 
Small intestinal perforation * 1  1/605 (0.17%)  1/611 (0.16%) 
Subileus * 1  0/605 (0.00%)  2/611 (0.33%) 
Colonic fistula * 1  1/605 (0.17%)  0/611 (0.00%) 
Duodenal obstruction * 1  1/605 (0.17%)  0/611 (0.00%) 
Duodenal ulcer haemorrhage * 1  0/605 (0.00%)  1/611 (0.16%) 
Enterocolitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Enterocutaneous fistula * 1  0/605 (0.00%)  1/611 (0.16%) 
Gastrointestinal hypomotility * 1  1/605 (0.17%)  0/611 (0.00%) 
Gastrointestinal perforation * 1  1/605 (0.17%)  0/611 (0.00%) 
Ileal perforation * 1  0/605 (0.00%)  1/611 (0.16%) 
Ileitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Large intestinal haemorrhage * 1  0/605 (0.00%)  1/611 (0.16%) 
Large intestinal obstruction * 1  0/605 (0.00%)  1/611 (0.16%) 
Lower gastrointestinal haemorrhage * 1  0/605 (0.00%)  1/611 (0.16%) 
Mallory-weiss syndrome * 1  0/605 (0.00%)  1/611 (0.16%) 
Mesenteric vein thrombosis * 1  0/605 (0.00%)  1/611 (0.16%) 
Neutropenic colitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Pancreatitis * 1  1/605 (0.17%)  0/611 (0.00%) 
Rectal obstruction * 1  0/605 (0.00%)  1/611 (0.16%) 
Rectal stenosis * 1  1/605 (0.17%)  0/611 (0.00%) 
General disorders     
Fatigue * 1  3/605 (0.50%)  2/611 (0.33%) 
Asthenia * 1  4/605 (0.66%)  5/611 (0.82%) 
Pyrexia * 1  15/605 (2.48%)  10/611 (1.64%) 
Oedema peripheral * 1  3/605 (0.50%)  0/611 (0.00%) 
Disease progression * 1  14/605 (2.31%)  16/611 (2.62%) 
Pain * 1  1/605 (0.17%)  2/611 (0.33%) 
Non-cardiac chest pain * 1  1/605 (0.17%)  2/611 (0.33%) 
Malaise * 1  0/605 (0.00%)  1/611 (0.16%) 
Thrombosis in device * 1  0/605 (0.00%)  2/611 (0.33%) 
General physical health deterioration * 1  1/605 (0.17%)  1/611 (0.16%) 
Medical device complication * 1  0/605 (0.00%)  1/611 (0.16%) 
Death * 1  1/605 (0.17%)  2/611 (0.33%) 
Suprapubic pain * 1  1/605 (0.17%)  0/611 (0.00%) 
Mucosal inflammation * 1  0/605 (0.00%)  1/611 (0.16%) 
Sudden death * 1  1/605 (0.17%)  0/611 (0.00%) 
Hepatobiliary disorders     
Hyperbilirubinaemia * 1  4/605 (0.66%)  2/611 (0.33%) 
Cholecystitis * 1  1/605 (0.17%)  4/611 (0.65%) 
Biliary colic * 1  1/605 (0.17%)  0/611 (0.00%) 
Cholangitis * 1  1/605 (0.17%)  1/611 (0.16%) 
Hepatic function abnormal * 1  1/605 (0.17%)  0/611 (0.00%) 
Jaundice cholestatic * 1  1/605 (0.17%)  0/611 (0.00%) 
Bile duct obstruction * 1  0/605 (0.00%)  1/611 (0.16%) 
Hepatic haemorrhage * 1  0/605 (0.00%)  1/611 (0.16%) 
Hepatitis * 1  1/605 (0.17%)  0/611 (0.00%) 
Hepatotoxicity * 1  1/605 (0.17%)  0/611 (0.00%) 
Immune system disorders     
Hypersensitivity * 1  2/605 (0.33%)  0/611 (0.00%) 
Infections and infestations     
Urinary tract infection * 1  3/605 (0.50%)  8/611 (1.31%) 
Upper respiratory tract infection * 1  0/605 (0.00%)  1/611 (0.16%) 
Pneumonia * 1  5/605 (0.83%)  11/611 (1.80%) 
Lower respiratory tract infection * 1  2/605 (0.33%)  1/611 (0.16%) 
Device related infection * 1  6/605 (0.99%)  5/611 (0.82%) 
Bronchitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Cystitis * 1  1/605 (0.17%)  0/611 (0.00%) 
Oral candidiasis * 1  0/605 (0.00%)  1/611 (0.16%) 
Neutropenic infection * 1  5/605 (0.83%)  4/611 (0.65%) 
Sinusitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Viral infection * 1  1/605 (0.17%)  0/611 (0.00%) 
Pharyngitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Respiratory tract infection * 1  0/605 (0.00%)  1/611 (0.16%) 
Sepsis * 1  5/605 (0.83%)  8/611 (1.31%) 
Gastroenteritis * 1  2/605 (0.33%)  1/611 (0.16%) 
Catheter site infection * 1  0/605 (0.00%)  3/611 (0.49%) 
Infection * 1  1/605 (0.17%)  1/611 (0.16%) 
Lobar pneumonia * 1  5/605 (0.83%)  0/611 (0.00%) 
Lung infection * 1  1/605 (0.17%)  1/611 (0.16%) 
Anal abscess * 1  1/605 (0.17%)  1/611 (0.16%) 
Diverticulitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Neutropenic sepsis * 1  0/605 (0.00%)  3/611 (0.49%) 
Perirectal abscess * 1  0/605 (0.00%)  3/611 (0.49%) 
Subcutaneous abscess * 1  0/605 (0.00%)  1/611 (0.16%) 
Abscess jaw * 1  0/605 (0.00%)  1/611 (0.16%) 
Clostridial infection * 1  0/605 (0.00%)  1/611 (0.16%) 
Oesophageal candidiasis * 1  0/605 (0.00%)  1/611 (0.16%) 
Septic shock * 1  0/605 (0.00%)  2/611 (0.33%) 
Appendicitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Bacterial sepsis * 1  0/605 (0.00%)  1/611 (0.16%) 
Beta haemolytic streptococcal infection * 1  0/605 (0.00%)  1/611 (0.16%) 
Bronchopneumonia * 1  1/605 (0.17%)  0/611 (0.00%) 
Device related sepsis * 1  0/605 (0.00%)  1/611 (0.16%) 
Emphysematous cystitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Enterocolitis infectious * 1  0/605 (0.00%)  1/611 (0.16%) 
Escherichia infection * 1  1/605 (0.17%)  0/611 (0.00%) 
Pelvic abscess * 1  0/605 (0.00%)  1/611 (0.16%) 
Perinephric abscess * 1  0/605 (0.00%)  1/611 (0.16%) 
Peritonitis bacterial * 1  0/605 (0.00%)  1/611 (0.16%) 
Pneumonia streptococcal * 1  0/605 (0.00%)  1/611 (0.16%) 
Rectal abscess * 1  0/605 (0.00%)  1/611 (0.16%) 
Staphylococcal sepsis * 1  0/605 (0.00%)  1/611 (0.16%) 
Viral diarrhoea * 1  1/605 (0.17%)  0/611 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  1/605 (0.17%)  0/611 (0.00%) 
Post procedural haemorrhage * 1  1/605 (0.17%)  2/611 (0.33%) 
Skin laceration * 1  1/605 (0.17%)  0/611 (0.00%) 
Gastrointestinal stoma complication * 1  0/605 (0.00%)  3/611 (0.49%) 
Head injury * 1  1/605 (0.17%)  0/611 (0.00%) 
Incisional hernia * 1  0/605 (0.00%)  1/611 (0.16%) 
Wound dehiscence * 1  1/605 (0.17%)  0/611 (0.00%) 
Ankle fracture * 1  0/605 (0.00%)  1/611 (0.16%) 
Femoral neck fracture * 1  1/605 (0.17%)  0/611 (0.00%) 
Femur fracture * 1  1/605 (0.17%)  0/611 (0.00%) 
Limb traumatic amputation * 1  0/605 (0.00%)  1/611 (0.16%) 
Pneumothorax traumatic * 1  1/605 (0.17%)  0/611 (0.00%) 
Subdural haematoma * 1  0/605 (0.00%)  1/611 (0.16%) 
Investigations     
Neutrophil count decreased * 1  0/605 (0.00%)  1/611 (0.16%) 
Blood creatinine increased * 1  2/605 (0.33%)  2/611 (0.33%) 
Blood bilirubin increased * 1  1/605 (0.17%)  0/611 (0.00%) 
Haemoglobin decreased * 1  0/605 (0.00%)  1/611 (0.16%) 
International normalised ratio increased * 1  0/605 (0.00%)  1/611 (0.16%) 
Blood creatine increased * 1  0/605 (0.00%)  1/611 (0.16%) 
C-reactive protein increased * 1  1/605 (0.17%)  0/611 (0.00%) 
Hepatic enzyme increased * 1  0/605 (0.00%)  1/611 (0.16%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/605 (0.33%)  3/611 (0.49%) 
Dehydration * 1  7/605 (1.16%)  24/611 (3.93%) 
Diabetes mellitus * 1  0/605 (0.00%)  1/611 (0.16%) 
Hypoglycaemia * 1  0/605 (0.00%)  2/611 (0.33%) 
Hyponatraemia * 1  0/605 (0.00%)  2/611 (0.33%) 
Failure to thrive * 1  1/605 (0.17%)  0/611 (0.00%) 
Hypoproteinaemia * 1  1/605 (0.17%)  0/611 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  4/605 (0.66%)  3/611 (0.49%) 
Bone pain * 1  1/605 (0.17%)  1/611 (0.16%) 
Musculoskeletal chest pain * 1  2/605 (0.33%)  0/611 (0.00%) 
Bursitis * 1  1/605 (0.17%)  0/611 (0.00%) 
Osteonecrosis of jaw * 1  0/605 (0.00%)  1/611 (0.16%) 
Pathological fracture * 1  1/605 (0.17%)  0/611 (0.00%) 
Fistula * 1  0/605 (0.00%)  1/611 (0.16%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastatic pain * 1  3/605 (0.50%)  2/611 (0.33%) 
Cancer pain * 1  1/605 (0.17%)  1/611 (0.16%) 
Tumour pain * 1  1/605 (0.17%)  1/611 (0.16%) 
Metastases to central nervous system * 1  1/605 (0.17%)  1/611 (0.16%) 
Benign neoplasm of cervix uteri * 1  0/605 (0.00%)  1/611 (0.16%) 
Bladder cancer * 1  0/605 (0.00%)  1/611 (0.16%) 
Tumour associated fever * 1  0/605 (0.00%)  1/611 (0.16%) 
Nervous system disorders     
Headache * 1  1/605 (0.17%)  3/611 (0.49%) 
Peripheral sensory neuropathy * 1  0/605 (0.00%)  1/611 (0.16%) 
Syncope * 1  3/605 (0.50%)  1/611 (0.16%) 
Presyncope * 1  0/605 (0.00%)  1/611 (0.16%) 
Transient ischaemic attack * 1  0/605 (0.00%)  2/611 (0.33%) 
Migraine * 1  0/605 (0.00%)  1/611 (0.16%) 
Spinal cord compression * 1  1/605 (0.17%)  0/611 (0.00%) 
Aphasia * 1  1/605 (0.17%)  0/611 (0.00%) 
Brachial plexopathy * 1  1/605 (0.17%)  0/611 (0.00%) 
Cerebrovascular accident * 1  0/605 (0.00%)  1/611 (0.16%) 
Coma * 1  0/605 (0.00%)  1/611 (0.16%) 
Convulsion * 1  0/605 (0.00%)  1/611 (0.16%) 
Disturbance in attention * 1  1/605 (0.17%)  0/611 (0.00%) 
Haemorrhage intracranial * 1  1/605 (0.17%)  0/611 (0.00%) 
Metabolic encephalopathy * 1  0/605 (0.00%)  1/611 (0.16%) 
Psychiatric disorders     
Anxiety * 1  0/605 (0.00%)  1/611 (0.16%) 
Depression * 1  0/605 (0.00%)  1/611 (0.16%) 
Confusional state * 1  2/605 (0.33%)  2/611 (0.33%) 
Hallucination * 1  0/605 (0.00%)  1/611 (0.16%) 
Mental status changes * 1  0/605 (0.00%)  1/611 (0.16%) 
Renal and urinary disorders     
Proteinuria * 1  0/605 (0.00%)  1/611 (0.16%) 
Haematuria * 1  2/605 (0.33%)  1/611 (0.16%) 
Urinary retention * 1  1/605 (0.17%)  4/611 (0.65%) 
Urinary incontinence * 1  1/605 (0.17%)  0/611 (0.00%) 
Hydronephrosis * 1  3/605 (0.50%)  1/611 (0.16%) 
Renal failure acute * 1  0/605 (0.00%)  2/611 (0.33%) 
Renal impairment * 1  0/605 (0.00%)  2/611 (0.33%) 
Renal vein thrombosis * 1  0/605 (0.00%)  1/611 (0.16%) 
Bladder neck obstruction * 1  0/605 (0.00%)  1/611 (0.16%) 
Nephrotic syndrome * 1  0/605 (0.00%)  1/611 (0.16%) 
Renal failure * 1  1/605 (0.17%)  1/611 (0.16%) 
Cystitis haemorrhagic * 1  0/605 (0.00%)  1/611 (0.16%) 
Nephrolithiasis * 1  1/605 (0.17%)  0/611 (0.00%) 
Obstructive uropathy * 1  1/605 (0.17%)  0/611 (0.00%) 
Urinary tract obstruction * 1  1/605 (0.17%)  0/611 (0.00%) 
Reproductive system and breast disorders     
Pelvic pain * 1  1/605 (0.17%)  0/611 (0.00%) 
Balanitis * 1  0/605 (0.00%)  1/611 (0.16%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  0/605 (0.00%)  2/611 (0.33%) 
Cough * 1  0/605 (0.00%)  1/611 (0.16%) 
Dyspnoea * 1  3/605 (0.50%)  3/611 (0.49%) 
Oropharyngeal pain * 1  0/605 (0.00%)  1/611 (0.16%) 
Pulmonary embolism * 1  12/605 (1.98%)  19/611 (3.11%) 
Pleural effusion * 1  0/605 (0.00%)  1/611 (0.16%) 
Pleuritic pain * 1  0/605 (0.00%)  1/611 (0.16%) 
Atelectasis * 1  0/605 (0.00%)  1/611 (0.16%) 
Interstitial lung disease * 1  2/605 (0.33%)  0/611 (0.00%) 
Pneumonitis * 1  1/605 (0.17%)  1/611 (0.16%) 
Pneumothorax * 1  0/605 (0.00%)  2/611 (0.33%) 
Acute pulmonary oedema * 1  0/605 (0.00%)  1/611 (0.16%) 
Acute respiratory distress syndrome * 1  0/605 (0.00%)  1/611 (0.16%) 
Acute respiratory failure * 1  0/605 (0.00%)  1/611 (0.16%) 
Pneumomediastinum * 1  0/605 (0.00%)  1/611 (0.16%) 
Pneumonia aspiration * 1  0/605 (0.00%)  1/611 (0.16%) 
Pulmonary artery thrombosis * 1  0/605 (0.00%)  1/611 (0.16%) 
Pulmonary hypertension * 1  0/605 (0.00%)  1/611 (0.16%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular * 1  0/605 (0.00%)  1/611 (0.16%) 
Vascular disorders     
Hypertension * 1  0/605 (0.00%)  10/611 (1.64%) 
Deep vein thrombosis * 1  7/605 (1.16%)  7/611 (1.15%) 
Hypotension * 1  0/605 (0.00%)  1/611 (0.16%) 
Jugular vein thrombosis * 1  2/605 (0.33%)  0/611 (0.00%) 
Vena cava thrombosis * 1  2/605 (0.33%)  2/611 (0.33%) 
Pelvic venous thrombosis * 1  2/605 (0.33%)  0/611 (0.00%) 
Orthostatic hypotension * 1  0/605 (0.00%)  1/611 (0.16%) 
Subclavian vein thrombosis * 1  2/605 (0.33%)  1/611 (0.16%) 
Circulatory collapse * 1  1/605 (0.17%)  1/611 (0.16%) 
Thrombophlebitis * 1  1/605 (0.17%)  0/611 (0.00%) 
Arterial thrombosis limb * 1  1/605 (0.17%)  0/611 (0.00%) 
Embolism arterial * 1  0/605 (0.00%)  1/611 (0.16%) 
Hypovolaemic shock * 1  0/605 (0.00%)  1/611 (0.16%) 
Superior vena caval occlusion * 1  0/605 (0.00%)  1/611 (0.16%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo/FOLFIRI Aflibercept/FOLFIRI
Affected / at Risk (%) Affected / at Risk (%)
Total   575/605 (95.04%)   599/611 (98.04%) 
Blood and lymphatic system disorders     
Neutropenia * 1  202/605 (33.39%)  229/611 (37.48%) 
Gastrointestinal disorders     
Diarrhoea * 1  335/605 (55.37%)  411/611 (67.27%) 
Nausea * 1  327/605 (54.05%)  322/611 (52.70%) 
Stomatitis * 1  199/605 (32.89%)  304/611 (49.75%) 
Vomiting * 1  199/605 (32.89%)  194/611 (31.75%) 
Abdominal pain * 1  141/605 (23.31%)  158/611 (25.86%) 
Constipation * 1  146/605 (24.13%)  135/611 (22.09%) 
Abdominal pain upper * 1  46/605 (7.60%)  63/611 (10.31%) 
Dyspepsia * 1  56/605 (9.26%)  50/611 (8.18%) 
Haemorrhoids * 1  13/605 (2.15%)  34/611 (5.56%) 
Proctalgia * 1  11/605 (1.82%)  32/611 (5.24%) 
General disorders     
Fatigue * 1  234/605 (38.68%)  292/611 (47.79%) 
Asthenia * 1  77/605 (12.73%)  109/611 (17.84%) 
Pyrexia * 1  73/605 (12.07%)  77/611 (12.60%) 
Oedema peripheral * 1  42/605 (6.94%)  52/611 (8.51%) 
Infections and infestations     
Urinary tract infection * 1  35/605 (5.79%)  51/611 (8.35%) 
Investigations     
Weight decreased * 1  87/605 (14.38%)  195/611 (31.91%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  143/605 (23.64%)  195/611 (31.91%) 
Dehydration * 1  12/605 (1.98%)  33/611 (5.40%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  69/605 (11.40%)  72/611 (11.78%) 
Arthralgia * 1  40/605 (6.61%)  31/611 (5.07%) 
Pain in extremity * 1  33/605 (5.45%)  34/611 (5.56%) 
Nervous system disorders     
Headache * 1  53/605 (8.76%)  136/611 (22.26%) 
Dizziness * 1  53/605 (8.76%)  36/611 (5.89%) 
Dysgeusia * 1  32/605 (5.29%)  42/611 (6.87%) 
Neuropathy peripheral * 1  30/605 (4.96%)  34/611 (5.56%) 
Lethargy * 1  28/605 (4.63%)  33/611 (5.40%) 
Psychiatric disorders     
Insomnia * 1  45/605 (7.44%)  47/611 (7.69%) 
Renal and urinary disorders     
Proteinuria * 1  9/605 (1.49%)  63/611 (10.31%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  45/605 (7.44%)  168/611 (27.50%) 
Dysphonia * 1  20/605 (3.31%)  155/611 (25.37%) 
Cough * 1  58/605 (9.59%)  67/611 (10.97%) 
Dyspnoea * 1  51/605 (8.43%)  69/611 (11.29%) 
Oropharyngeal pain * 1  19/605 (3.14%)  45/611 (7.36%) 
Rhinorrhoea * 1  11/605 (1.82%)  38/611 (6.22%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  182/605 (30.08%)  164/611 (26.84%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  26/605 (4.30%)  67/611 (10.97%) 
Rash * 1  35/605 (5.79%)  41/611 (6.71%) 
Skin hyperpigmentation * 1  17/605 (2.81%)  50/611 (8.18%) 
Hyperhidrosis * 1  33/605 (5.45%)  17/611 (2.78%) 
Vascular disorders     
Hypertension * 1  65/605 (10.74%)  250/611 (40.92%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 days for abstracts) in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed ninety days).
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: International Clinical Development Study Director
Organization: sanofi-aventis
EMail: contact-us@sanofi.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00561470     History of Changes
Other Study ID Numbers: EFC10262
EudraCT 2007-000820-42
First Submitted: November 20, 2007
First Posted: November 21, 2007
Results First Submitted: August 17, 2012
Results First Posted: September 28, 2012
Last Update Posted: September 28, 2012