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Trial record 74 of 78 for:    sanofi-aventis and sweden

Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer

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: NCT00327171
Recruitment Status : Completed
First Posted : May 18, 2006
Results First Posted : October 18, 2012
Last Update Posted : June 7, 2016
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Neoplasms
Cancer of the Ovary
Intervention Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Enrollment 218
Recruitment Details 218 participants were randomized in this study. Three participants in the 2 mg/kg treatment group did not receive any study medication.
Pre-assignment Details  
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Period Title: Overall Study
Started 109 109
Completed 1 [1] 0 [1]
Not Completed 108 109
Reason Not Completed
Did not receive study medication             3             0
Adverse Event             23             23
Disease progression/lack of efficacy             68             69
Investigator/participant request             1             8
Clinical progression             12             8
Undisclosed history of ischemia             0             1
Other             1             0
[1]
Participants received treatment until they met treatment discontinuation criteria
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg Total
Hide Arm/Group Description Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks Total of all reporting groups
Overall Number of Baseline Participants 109 109 218
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 109 participants 109 participants 218 participants
<35 years 3 3 6
>=35 to <45 years 10 6 16
>=45 to <55 years 21 25 46
>=55 to <65 years 37 43 80
>=65 to <75 years 32 25 57
>=75 years 6 7 13
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 109 participants 109 participants 218 participants
Female
109
 100.0%
109
 100.0%
218
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 109 participants 109 participants 218 participants
Caucasian 104 107 211
Black 3 1 4
Asian, Oriental 1 1 2
Unknown or Not Reported 1 0 1
1.Primary Outcome
Title Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort
Hide Description

OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference.

Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Simon's cohort: The first 67 evaluable participants, based on Simon’s two-stage design that required 67 evaluable participants per group to maintain a targeted 80% power for Objective response rate versus historical controls.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 67 67
Measure Type: Number
Unit of Measure: participants
0 3
2.Primary Outcome
Title Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population
Hide Description

OR included Complete Response (CR) and Partial Response (PR). Per RECIST, CR was disappearance of all target or non-target lesions, or normalization of tumor marker levels (for non-target lesions) and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with baseline sum LD as reference.

Tumors were assessed by an independent third-party core imaging laboratory evaluating the chest, abdomen, and pelvis by Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and responses were confirmed by repeat tumor imaging 4-6 weeks later.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 106 109
Measure Type: Number
Unit of Measure: participants
1 5
3.Secondary Outcome
Title Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC
Hide Description

CBR was defined as having a Stable disease (SD) for >= 6 months or a confirmed OR (PR or CR). Based on RECIST:

  • SD was neither a sufficient shrinkage of the target lesions to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), the persistence of non-target lesions or the maintenance of tumor marker level above the normal limits (for non-target lesions)
  • CR was the disappearance of all target or non-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD.
Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Simon's cohort: The first 67 evaluable participants, based on Simon’s two-stage design that required 67 evaluable participants per group to maintain a targeted 80% power for Objective response rate versus historical controls.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 67 67
Measure Type: Number
Unit of Measure: participants
12 7
4.Secondary Outcome
Title Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC)
Hide Description

DR was defined as the time interval from the first documentation of CR or PR to the date of tumor progression (or disease progression) as determined by RECIST, or death from any cause, whichever was earlier.

Based on RECIST, progressive disease was at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, the appearance of one or more new target or non-target lesions, or the unequivocal progression of existing non-target lesions.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 1 5
Mean (Standard Deviation)
Unit of Measure: days
164 [1]   (NA) 149.8  (70.4)
[1]
NA: Not calculable since only one participant achieved CR or PR
5.Secondary Outcome
Title Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition
Hide Description TMRR was the proportion of evaluable participants achieving a cancer antigen -125 (CA-125) response based on GCIG definition. A response to CA-125 occurred if after two elevated levels before therapy there was at least a 50% decrease in a post-treatment serum sample, which was confirmed by an independent sample collected 21 days or later that was =< 110% of the post-treatment serum sample.
Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least part of one dose of aflibercept, had a baseline tumor assessment, had a valid CA-125 assessment (requiring at least two pretreatment sample and 2 post-treatment samples), did not receive mouse antibodies and had no medical or surgical interference with their peritoneum or pleura in the previous 28 days.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 61 69
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
11.5
(4.7 to 22.2)
11.6
(5.1 to 21.6)
6.Secondary Outcome
Title Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC
Hide Description

TTP was defined as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST. TTP was estimated from Kaplan-Meier curves.

For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 106 109
Overall Number of Units Analyzed
Type of Units Analyzed: Tumor Progression Events
66 66
Median (95% Confidence Interval)
Unit of Measure: weeks
13.1
(12.1 to 16.7)
12.7
(12 to 18.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aflibercept 2.0 mg/kg, Aflibercept 4.0 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5043
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.123
Confidence Interval (2-Sided) 95%
0.80 to 1.58
Estimation Comments Estimated using Cox proportional Hazard model using treatment as the factor
7.Secondary Outcome
Title Time to Tumor Marker (CA-125) Progression (TTMP)
Hide Description

TTMP was the time interval from the date of randomization to the date of tumor marker progression as was defined by GCIG for the evaluable participants. TTMP was estimated using Kaplan-Meier curves.

For a participant who did not reach tumor marker progression (TMP) during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid assessment of CA-125 (requiring at least one pretreatment sample and 2 post-treatment samples).
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 76 84
Overall Number of Units Analyzed
Type of Units Analyzed: Tumor Marker Progression events
15 20
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(24.1 to NA)
NA [1] 
(22.7 to NA)
[1]
The value was not calculable due to the limited number of events.
8.Secondary Outcome
Title Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC.
Hide Description

PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier.

The number of participants with tumor/disease progression are reported. Participants who did not reach tumor progression during study, or had no valid post-baseline tumor burden assessment due to early termination, were censored in the PFS analysis.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 106 109
Measure Type: Number
Unit of Measure: participants
With disease progression as the first event 66 66
Death without disease progression 16 23
Censored due to drop-out 18 14
Censored at study cut-off 6 6
9.Secondary Outcome
Title Progression-free Survival (PFS) Time Based on Analysis by the IRC
Hide Description

PFS was as the time interval measured from the date of randomization to the date of tumor progression as determined by RECIST or death from any cause, whichever was earlier. PFS was estimated using Kaplan-Meier curves.

For a participant who did not reach tumor progression during study, the censoring date was the date of the last valid tumor burden assessment or the date of study cut-off, whichever was earlier. If the participant had no valid post-baseline tumor burden assessment due to early termination, the censoring date was the date of randomization.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 106 109
Overall Number of Units Analyzed
Type of Units Analyzed: PFS Events
82 89
Median (95% Confidence Interval)
Unit of Measure: weeks
13.0
(11.7 to 16.7)
13.3
(11.2 to 18.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aflibercept 2.0 mg/kg, Aflibercept 4.0 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5592
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.093
Confidence Interval (2-Sided) 95%
0.81 to 1.48
Estimation Comments Estimated using Cox proportional Hazard model using treatment as the factor (4mg/kg vs. 2mg/kg)
10.Secondary Outcome
Title Overall Survival (OS) Time
Hide Description

OS was the time interval between randomization and the date of death from any cause. OS was estimated using Kaplan-Meier curves

A participant was censored for the OS analysis if the participant were alive during the study. The censoring date was either at the date that the participant was last known to be alive or the date of study cut-off, whichever was earlier.

Time Frame From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable population: All participants with advanced ovarian epithelial carcinoma who were randomized, underwent baseline tumor assessment, and received at least part of one dose of aflibercept.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 106 109
Overall Number of Units Analyzed
Type of Units Analyzed: Events (Death)
50 58
Median (95% Confidence Interval)
Unit of Measure: weeks
59.0
(41.6 to 84.1)
49.3
(37.4 to 62.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aflibercept 2.0 mg/kg, Aflibercept 4.0 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5457
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.124
Confidence Interval (2-Sided) 95%
0.77 to 1.64
Estimation Comments Estimated using Cox proportional Hazard model using treatment as the factor (4 mg/kg vs. 2mg/kg)
11.Secondary Outcome
Title Overall Safety - 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 up to 30+/-5 days after treatment discontinuation, or up to recovery or stabilization of a followed-up adverse event
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: All randomized participants who received at least part of one dose of study treatment.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 106 109
Measure Type: Number
Unit of Measure: participants
With any TEAE 106 108
With any serious TEAE 50 55
With any TEAE leading to death 14 14
With TEAE leading to treatment discontinuation 23 24
12.Secondary Outcome
Title Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire
Hide Description The FACT-O questionnaire consists of 38 scored questions (scored from 0-4) that address physical well-being, social/family well-being, emotional well-being, functional well-being and some additional concerns which relate specifically to ovarian cancer symptoms. For each question, higher scores reflect a better quality of life. The total FACT-O score ranges from 0-152, with 152 indicating the best outcome.
Time Frame On Day 1 of Cycle 1 (baseline) , and after Day 14 of Cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable FACT-O questionnaires.
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description:
Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks
Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
Overall Number of Participants Analyzed 97 104
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline (N=97, N=104) 105.3  (20.0) 101.1  (22)
Change (baseline to Cycle 2-Day 14) (N=79, N=77) -1.1  (12.7) -2.8  (13.9)
Time Frame From treatment initiation to June 9, 2010
Adverse Event Reporting Description Safety population: All randomized participants who received at least part of one dose of study treatment.
 
Arm/Group Title Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Hide Arm/Group Description Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept intravenously every two weeks Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept intravenously every two weeks
All-Cause Mortality
Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   51/106 (48.11%)   56/109 (51.38%) 
Blood and lymphatic system disorders     
Anaemia * 1  2/106 (1.89%)  1/109 (0.92%) 
Thrombocytopenia * 1  1/106 (0.94%)  0/109 (0.00%) 
Thrombotic thrombocytopenic purpura * 1  0/106 (0.00%)  1/109 (0.92%) 
Cardiac disorders     
Angina pectoris * 1  1/106 (0.94%)  0/109 (0.00%) 
Cardio-respiratory arrest * 1  1/106 (0.94%)  0/109 (0.00%) 
Congestive cardiomyopathy * 1  1/106 (0.94%)  0/109 (0.00%) 
Left ventricular dysfunction * 1  0/106 (0.00%)  1/109 (0.92%) 
Ear and labyrinth disorders     
Vertigo * 1  0/106 (0.00%)  1/109 (0.92%) 
Eye disorders     
Blindness transient * 1  0/106 (0.00%)  1/109 (0.92%) 
Gastrointestinal disorders     
Abdominal pain * 1  4/106 (3.77%)  6/109 (5.50%) 
Ascites * 1  1/106 (0.94%)  0/109 (0.00%) 
Colonic obstruction * 1  1/106 (0.94%)  0/109 (0.00%) 
Crohn's disease * 1  1/106 (0.94%)  0/109 (0.00%) 
Diarrhoea * 1  1/106 (0.94%)  1/109 (0.92%) 
Gastrointestinal haemorrhage * 1  0/106 (0.00%)  1/109 (0.92%) 
Gastrointestinal necrosis * 1  1/106 (0.94%)  0/109 (0.00%) 
Gastrointestinal obstruction * 1  2/106 (1.89%)  1/109 (0.92%) 
Intestinal obstruction * 1  10/106 (9.43%)  6/109 (5.50%) 
Intestinal perforation * 1  1/106 (0.94%)  2/109 (1.83%) 
Melaena * 1  1/106 (0.94%)  0/109 (0.00%) 
Nausea * 1  3/106 (2.83%)  0/109 (0.00%) 
Small intestinal obstruction * 1  0/106 (0.00%)  2/109 (1.83%) 
Subileus * 1  0/106 (0.00%)  2/109 (1.83%) 
Vomiting * 1  2/106 (1.89%)  2/109 (1.83%) 
General disorders     
Asthenia * 1  1/106 (0.94%)  2/109 (1.83%) 
Disease progression * 1  3/106 (2.83%)  7/109 (6.42%) 
Fatigue * 1  0/106 (0.00%)  1/109 (0.92%) 
General physical health deterioration * 1  0/106 (0.00%)  2/109 (1.83%) 
Pyrexia * 1  2/106 (1.89%)  2/109 (1.83%) 
Sudden death * 1  0/106 (0.00%)  1/109 (0.92%) 
Hepatobiliary disorders     
Jaundice cholestatic * 1  1/106 (0.94%)  0/109 (0.00%) 
Infections and infestations     
Abscess intestinal * 1  0/106 (0.00%)  1/109 (0.92%) 
Appendicitis * 1  0/106 (0.00%)  1/109 (0.92%) 
Catheter site infection * 1  0/106 (0.00%)  1/109 (0.92%) 
Clostridial infection * 1  0/106 (0.00%)  1/109 (0.92%) 
Clostridium difficile colitis * 1  0/106 (0.00%)  1/109 (0.92%) 
Device related infection * 1  1/106 (0.94%)  0/109 (0.00%) 
Febrile infection * 1  1/106 (0.94%)  1/109 (0.92%) 
Gastroenteritis salmonella * 1  1/106 (0.94%)  0/109 (0.00%) 
Hepatitis a * 1  0/106 (0.00%)  1/109 (0.92%) 
Peritonitis bacterial * 1  0/106 (0.00%)  1/109 (0.92%) 
Pneumonia * 1  2/106 (1.89%)  2/109 (1.83%) 
Pneumonia streptococcal * 1  1/106 (0.94%)  0/109 (0.00%) 
Pyelonephritis * 1  0/106 (0.00%)  1/109 (0.92%) 
Sepsis * 1  1/106 (0.94%)  0/109 (0.00%) 
Septic shock * 1  1/106 (0.94%)  0/109 (0.00%) 
Urinary tract infection * 1  1/106 (0.94%)  0/109 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  0/106 (0.00%)  1/109 (0.92%) 
Narcotic intoxication * 1  0/106 (0.00%)  1/109 (0.92%) 
Wound dehiscence * 1  0/106 (0.00%)  1/109 (0.92%) 
Investigations     
Blood alkaline phosphatase increased * 1  1/106 (0.94%)  0/109 (0.00%) 
Blood creatinine increased * 1  1/106 (0.94%)  0/109 (0.00%) 
Gamma-glutamyltransferase increased * 1  1/106 (0.94%)  0/109 (0.00%) 
Hepatic enzyme increased * 1  1/106 (0.94%)  0/109 (0.00%) 
International normalised ratio increased * 1  0/106 (0.00%)  1/109 (0.92%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/106 (1.89%)  0/109 (0.00%) 
Dehydration * 1  4/106 (3.77%)  2/109 (1.83%) 
Hypoalbuminaemia * 1  1/106 (0.94%)  0/109 (0.00%) 
Hyponatraemia * 1  1/106 (0.94%)  1/109 (0.92%) 
Type 1 diabetes mellitus * 1  0/106 (0.00%)  1/109 (0.92%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/106 (0.00%)  1/109 (0.92%) 
Musculoskeletal chest pain * 1  0/106 (0.00%)  1/109 (0.92%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cardiac myxoma * 1  1/106 (0.94%)  0/109 (0.00%) 
Malignant pleural effusion * 1  1/106 (0.94%)  0/109 (0.00%) 
Metastases to central nervous system * 1  0/106 (0.00%)  2/109 (1.83%) 
Metastases to lymph nodes * 1  1/106 (0.94%)  0/109 (0.00%) 
Metastases to small intestine * 1  0/106 (0.00%)  1/109 (0.92%) 
Nervous system disorders     
Grand mal convulsion * 1  0/106 (0.00%)  1/109 (0.92%) 
Headache * 1  1/106 (0.94%)  2/109 (1.83%) 
Hypertensive encephalopathy * 1  0/106 (0.00%)  1/109 (0.92%) 
Polyneuropathy * 1  0/106 (0.00%)  1/109 (0.92%) 
Syncope * 1  1/106 (0.94%)  0/109 (0.00%) 
Transient ischaemic attack * 1  1/106 (0.94%)  0/109 (0.00%) 
Renal and urinary disorders     
Hydronephrosis * 1  1/106 (0.94%)  0/109 (0.00%) 
Nephrotic syndrome * 1  1/106 (0.94%)  0/109 (0.00%) 
Proteinuria * 1  1/106 (0.94%)  1/109 (0.92%) 
Renal failure * 1  3/106 (2.83%)  3/109 (2.75%) 
Renal failure acute * 1  0/106 (0.00%)  1/109 (0.92%) 
Urinary retention * 1  1/106 (0.94%)  0/109 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  1/106 (0.94%)  0/109 (0.00%) 
Chronic obstructive pulmonary disease * 1  0/106 (0.00%)  1/109 (0.92%) 
Dyspnoea * 1  2/106 (1.89%)  4/109 (3.67%) 
Hypoxia * 1  1/106 (0.94%)  0/109 (0.00%) 
Pleural effusion * 1  3/106 (2.83%)  1/109 (0.92%) 
Pneumonia aspiration * 1  0/106 (0.00%)  1/109 (0.92%) 
Pulmonary embolism * 1  1/106 (0.94%)  2/109 (1.83%) 
Pulmonary oedema * 1  0/106 (0.00%)  1/109 (0.92%) 
Respiratory failure * 1  1/106 (0.94%)  0/109 (0.00%) 
Skin and subcutaneous tissue disorders     
Erythema * 1  0/106 (0.00%)  1/109 (0.92%) 
Vascular disorders     
Deep vein thrombosis * 1  0/106 (0.00%)  1/109 (0.92%) 
Hypertension * 1  4/106 (3.77%)  6/109 (5.50%) 
Phlebitis * 1  0/106 (0.00%)  1/109 (0.92%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aflibercept 2.0 mg/kg Aflibercept 4.0 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   105/106 (99.06%)   106/109 (97.25%) 
Blood and lymphatic system disorders     
Anaemia * 1  6/106 (5.66%)  2/109 (1.83%) 
Gastrointestinal disorders     
Abdominal pain * 1  36/106 (33.96%)  40/109 (36.70%) 
Abdominal pain upper * 1  14/106 (13.21%)  17/109 (15.60%) 
Constipation * 1  37/106 (34.91%)  27/109 (24.77%) 
Diarrhoea * 1  31/106 (29.25%)  39/109 (35.78%) 
Dry mouth * 1  6/106 (5.66%)  4/109 (3.67%) 
Intestinal obstruction * 1  8/106 (7.55%)  4/109 (3.67%) 
Nausea * 1  44/106 (41.51%)  43/109 (39.45%) 
Stomatitis * 1  10/106 (9.43%)  8/109 (7.34%) 
Toothache * 1  9/106 (8.49%)  7/109 (6.42%) 
Vomiting * 1  38/106 (35.85%)  30/109 (27.52%) 
General disorders     
Asthenia * 1  30/106 (28.30%)  27/109 (24.77%) 
Fatigue * 1  42/106 (39.62%)  44/109 (40.37%) 
Mucosal inflammation * 1  13/106 (12.26%)  19/109 (17.43%) 
Oedema peripheral * 1  12/106 (11.32%)  12/109 (11.01%) 
Pyrexia * 1  18/106 (16.98%)  21/109 (19.27%) 
Infections and infestations     
Nasopharyngitis * 1  7/106 (6.60%)  9/109 (8.26%) 
Urinary tract infection * 1  13/106 (12.26%)  5/109 (4.59%) 
Investigations     
Weight decreased * 1  8/106 (7.55%)  11/109 (10.09%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  42/106 (39.62%)  30/109 (27.52%) 
Dehydration * 1  3/106 (2.83%)  9/109 (8.26%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  25/106 (23.58%)  28/109 (25.69%) 
Back pain * 1  15/106 (14.15%)  10/109 (9.17%) 
Muscle spasms * 1  2/106 (1.89%)  7/109 (6.42%) 
Musculoskeletal pain * 1  15/106 (14.15%)  13/109 (11.93%) 
Myalgia * 1  8/106 (7.55%)  17/109 (15.60%) 
Neck pain * 1  8/106 (7.55%)  6/109 (5.50%) 
Pain in extremity * 1  9/106 (8.49%)  8/109 (7.34%) 
Nervous system disorders     
Dizziness * 1  9/106 (8.49%)  12/109 (11.01%) 
Headache * 1  54/106 (50.94%)  54/109 (49.54%) 
Neuropathy peripheral * 1  8/106 (7.55%)  4/109 (3.67%) 
Paraesthesia * 1  6/106 (5.66%)  8/109 (7.34%) 
Psychiatric disorders     
Anxiety * 1  4/106 (3.77%)  7/109 (6.42%) 
Depression * 1  3/106 (2.83%)  7/109 (6.42%) 
Insomnia * 1  8/106 (7.55%)  11/109 (10.09%) 
Renal and urinary disorders     
Proteinuria * 1  21/106 (19.81%)  23/109 (21.10%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  10/106 (9.43%)  21/109 (19.27%) 
Dysphonia * 1  39/106 (36.79%)  46/109 (42.20%) 
Dyspnoea * 1  15/106 (14.15%)  20/109 (18.35%) 
Epistaxis * 1  8/106 (7.55%)  21/109 (19.27%) 
Oropharyngeal pain * 1  7/106 (6.60%)  11/109 (10.09%) 
Rhinorrhoea * 1  4/106 (3.77%)  7/109 (6.42%) 
Skin and subcutaneous tissue disorders     
Nail disorder * 1  4/106 (3.77%)  6/109 (5.50%) 
Rash * 1  10/106 (9.43%)  9/109 (8.26%) 
Vascular disorders     
Hypertension * 1  60/106 (56.60%)  57/109 (52.29%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
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 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
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00327171     History of Changes
Other Study ID Numbers: ARD6122
AVE0005
First Submitted: May 16, 2006
First Posted: May 18, 2006
Results First Submitted: August 17, 2012
Results First Posted: October 18, 2012
Last Update Posted: June 7, 2016