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Trial record 68 of 78 for:    sanofi-aventis and sweden

A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (VITAL)

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: NCT00532155
Recruitment Status : Completed
First Posted : September 20, 2007
Results First Posted : January 1, 2013
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: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Carcinoma
Non Small Cell Lung
Interventions Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Drug: Placebo
Drug: Docetaxel (Taxotere®)
Drug: Dexamethasone (pre- and post-medication for docetaxel)
Enrollment 913
Recruitment Details  
Pre-assignment Details A total of 1130 participants signed an informed consent to enter the study. Amongst these, 913 were randomized to the two arms in this study. 217 participants were screen failures.
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel
Hide Arm/Group Description Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal. Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Period Title: Overall Study
Started 457 456
SAFETY POPULATION 455 450
Completed 0 [1] 0 [1]
Not Completed 457 456
Reason Not Completed
Adverse Event             66             123
Lack of Efficacy             332             255
Protocol Violation             1             3
Lost to Follow-up             2             0
Physician Decision             16             15
Withdrawal by Subject             23             44
Consent withdrawn             5             7
Moved             1             0
Pre-existing brain metastasis (by MRI)             1             0
Occurence of a second cancer             0             1
Occurence of a secondary cancer             0             1
Promotor ended study             1             0
Progressive disease (by incorrect scan)             0             1
Had brain metastasis, was mis-randomized             1             0
Study stopped             1             0
Study terminated by sponsor             1             0
Study termination stop further treatment             4             0
Did not receive study medication             2             6
[1]
Participants continued treatment until they met treatment discontinuation criteria
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel Total
Hide Arm/Group Description Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal. Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant’s refusal. Total of all reporting groups
Overall Number of Baseline Participants 457 456 913
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 457 participants 456 participants 913 participants
59.6  (9.4) 59.6  (9.5) 59.6  (9.4)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 457 participants 456 participants 913 participants
<65 years 316 315 631
>= and <75 years 122 121 243
>=75 years 19 20 39
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 457 participants 456 participants 913 participants
Male 300 305 605
Female 157 151 308
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 457 participants 456 participants 913 participants
Caucasian/White 405 411 816
Black 10 7 17
Asian/Oriental 40 34 74
Other 2 4 6
Body Surface Area (BSA)  
Mean (Standard Deviation)
Unit of measure:  M²
Number Analyzed 457 participants 456 participants 913 participants
1.8  (0.2) 1.8  (0.2) 1.8  (0.2)
Prior Bevacizumab (as per IVRS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 457 participants 456 participants 913 participants
Yes 53 51 104
No 404 405 809
[1]
Measure Description: Number of participants who had received prior bevacizumab as per interactive voice response system (IVRS).
Eastern Cooperative Oncology Group (ECOG) performance status score (as per IVRS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 457 participants 456 participants 913 participants
Participants with ECOG Score = 0 151 149 300
Participants with ECOG Score = 1 283 286 569
Participants with ECOG Score = 2 23 21 44
[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.
1.Primary Outcome
Title Overall Survival (OS)
Hide Description

OS was time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, overall survival time was censored at the last date the participant was known to be alive, or the study cutoff date, whichever was earlier. The cut-off date for the OS was date when 687 deaths were observed.

OS was estimated from Kaplan-Meier Curves.

Time Frame Baseline to the date when 687 deaths occurred (26 January 2011)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel
Hide Arm/Group Description:
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Number of Participants Analyzed 457 456
Overall Number of Units Analyzed
Type of Units Analyzed: Events (Death)
344 343
Median (95% Confidence Interval)
Unit of Measure: months
10.41
(9.199 to 11.860)
10.05
(9.166 to 11.598)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Docetaxel, Aflibercept/Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8985
Comments [Not Specified]
Method Stratified log-rank test
Comments Stratified on ECOG Performance Status (0 vs 1 vs 2) and Prior Bevacizumab (yes vs no) according to IVRS.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.868 to 1.174
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description

PFS was defined as the time interval between the date of randomization and the time of occurrence of the first radiological tumor progression detected by a computer tomography (CT) scan and /or by Magnetic Resonance Imaging (MRI); or death due to any cause; whichever was earlier. Participants without disease progression were censored at the earliest date between their last valid tumour assessment and the data cutoff date.

PFS was estimated from Kaplan-Meier Curves.

Time Frame Baseline to data cut-off (26 January 2011)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population. The results are based on a total of 865 PFS events (434 in the placebo group and 431 in the aflibercept group) at the time of cutoff.
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel
Hide Arm/Group Description:
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Number of Participants Analyzed 457 456
Overall Number of Units Analyzed
Type of Units Analyzed: PFS Events
434 431
Median (95% Confidence Interval)
Unit of Measure: months
4.11
(3.515 to 4.337)
5.19
(4.370 to 5.552)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Docetaxel, Aflibercept/Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0035
Comments [Not Specified]
Method Stratified Log-Rank test
Comments Stratified on ECOG Performance Status (0 vs 1 vs 2) and Prior Bevacizumab (yes vs no) according to IVRS.
Method of Estimation Estimation Parameter Stratified Hazard ratio
Estimated Value 0.819
Confidence Interval (2-Sided) 95%
0.716 to 0.937
Estimation Comments Stratified on ECOG Performance Status (0 vs 1 vs 2) and Prior Bevacizumab (yes vs no) according to IVRS.
3.Secondary Outcome
Title Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria
Hide Description

Participants with OR were those who had a confirmed complete response [CR] or a confirmed partial response [PR], based on RECIST criteria, in which

  • CR refected the disappearance of all tumor lesions (with no new tumors)
  • PR reflected a pre-defined decrease in tumor burden - a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
  • OR was CR + PR The response rate was the percent of participants with a response.

To determine a response, tumors were assessed by the investigators 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 Baseline to data cut-off (26 January 2011)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable population: All ITT participants with measurable disease at study entry, and with at least one valid post baseline tumor evaluation, except if the participant died due to progressive disease or had documented (ie, radiological) progression before having any post-baseline tumor evaluation.
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel
Hide Arm/Group Description:
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Number of Participants Analyzed 406 404
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response (CR) rate 0.2 0.2
Partial Response (PR) rate 8.6 23.0
Overall Response (OR) rate 8.9 38.6
4.Secondary Outcome
Title Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS)
Hide Description HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).
Time Frame Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with questionnaires evaluable for LCSS.
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel
Hide Arm/Group Description:
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Number of Participants Analyzed 457 456
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (N=431, N=428) 29.52  (17.03) 31.54  (18.03)
Cycle 2 (N=329, N=315) 29.50  (16.72) 30.54  (16.78)
Cycle 4 (N=211, N=240) 27.67  (16.24) 29.61  (16.92)
End of treatment (N=254, N=240) 34.82  (18.34) 36.07  (18.81)
5.Secondary Outcome
Title Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI)
Hide Description HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies, and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).
Time Frame Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with questionnaires evaluable for ABSI.
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel
Hide Arm/Group Description:
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.
Overall Number of Participants Analyzed 457 456
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (N=429, N=429) 26.17  (16.30) 28.24  (16.91)
Cycle 2 (N=327, N=316) 26.23  (15.93) 27.05  (15.92)
Cycle 4 (N=211, N=241) 24.52  (15.22) 26.19  (16.38)
End of treatment (N=253, N=239) 30.73  (17.26) 31.19  (18.12)
Time Frame From treatment initiation to October 21, 2011
Adverse Event Reporting Description A death event was reported as an SAE if it occurred within 30 days from end of study treatment, or if it occurred more than 30 days after the end of study treatment, and was due to adverse event. Death due to disease progression, 30 days after the end of study treatment is part of the efficacy endpoints (OS and PFS), but not the safety endpoints.
 
Arm/Group Title Placebo/Docetaxel Aflibercept/Docetaxel
Hide Arm/Group Description Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal. Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant’s refusal.
All-Cause Mortality
Placebo/Docetaxel Aflibercept/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo/Docetaxel Aflibercept/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   159/453 (35.10%)   218/452 (48.23%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  17/453 (3.75%)  21/452 (4.65%) 
Neutropenia * 1  7/453 (1.55%)  16/452 (3.54%) 
Anaemia * 1  6/453 (1.32%)  3/452 (0.66%) 
Leukopenia * 1  1/453 (0.22%)  2/452 (0.44%) 
Thrombocytopenia * 1  0/453 (0.00%)  1/452 (0.22%) 
Thrombotic microangiopathy * 1  0/453 (0.00%)  1/452 (0.22%) 
Granulocytopenia * 1  1/453 (0.22%)  0/452 (0.00%) 
Leukocytosis * 1  1/453 (0.22%)  0/452 (0.00%) 
Cardiac disorders     
Tachycardia * 1  1/453 (0.22%)  1/452 (0.22%) 
Atrial fibrillation * 1  1/453 (0.22%)  4/452 (0.88%) 
Supraventricular tachycardia * 1  0/453 (0.00%)  2/452 (0.44%) 
Myocardial infarction * 1  2/453 (0.44%)  0/452 (0.00%) 
Pericardial effusion * 1  1/453 (0.22%)  0/452 (0.00%) 
Acute myocardial infarction * 1  0/453 (0.00%)  1/452 (0.22%) 
Myocardial ischaemia * 1  0/453 (0.00%)  1/452 (0.22%) 
Ear and labyrinth disorders     
Deafness * 1  0/453 (0.00%)  1/452 (0.22%) 
Meniere's disease * 1  1/453 (0.22%)  0/452 (0.00%) 
Eye disorders     
Diplopia * 1  0/453 (0.00%)  1/452 (0.22%) 
Gastrointestinal disorders     
Stomatitis * 1  0/453 (0.00%)  13/452 (2.88%) 
Diarrhoea * 1  3/453 (0.66%)  8/452 (1.77%) 
Nausea * 1  2/453 (0.44%)  1/452 (0.22%) 
Constipation * 1  2/453 (0.44%)  1/452 (0.22%) 
Vomiting * 1  1/453 (0.22%)  1/452 (0.22%) 
Abdominal pain * 1  2/453 (0.44%)  1/452 (0.22%) 
Dysphagia * 1  0/453 (0.00%)  3/452 (0.66%) 
Odynophagia * 1  0/453 (0.00%)  1/452 (0.22%) 
Oesophagitis * 1  1/453 (0.22%)  0/452 (0.00%) 
Gastritis * 1  1/453 (0.22%)  0/452 (0.00%) 
Gastrointestinal inflammation * 1  0/453 (0.00%)  1/452 (0.22%) 
Periodontitis * 1  1/453 (0.22%)  0/452 (0.00%) 
Diverticular perforation * 1  0/453 (0.00%)  2/452 (0.44%) 
Enteritis * 1  0/453 (0.00%)  1/452 (0.22%) 
Gastric ulcer * 1  0/453 (0.00%)  1/452 (0.22%) 
Intestinal obstruction * 1  1/453 (0.22%)  1/452 (0.22%) 
Large intestine perforation * 1  1/453 (0.22%)  1/452 (0.22%) 
Duodenal ulcer haemorrhage * 1  1/453 (0.22%)  0/452 (0.00%) 
Gastric haemorrhage * 1  1/453 (0.22%)  0/452 (0.00%) 
Gastrointestinal perforation * 1  0/453 (0.00%)  1/452 (0.22%) 
Ileus * 1  1/453 (0.22%)  0/452 (0.00%) 
Impaired gastric emptying * 1  1/453 (0.22%)  0/452 (0.00%) 
Intestinal perforation * 1  0/453 (0.00%)  1/452 (0.22%) 
Intussusception * 1  0/453 (0.00%)  1/452 (0.22%) 
Pancreatitis acute * 1  0/453 (0.00%)  1/452 (0.22%) 
Periproctitis * 1  0/453 (0.00%)  1/452 (0.22%) 
Peritonitis * 1  0/453 (0.00%)  1/452 (0.22%) 
Small intestinal obstruction * 1  0/453 (0.00%)  1/452 (0.22%) 
Small intestinal perforation * 1  0/453 (0.00%)  1/452 (0.22%) 
General disorders     
Fatigue * 1  1/453 (0.22%)  4/452 (0.88%) 
Asthenia * 1  2/453 (0.44%)  2/452 (0.44%) 
Pyrexia * 1  2/453 (0.44%)  5/452 (1.11%) 
Oedema peripheral * 1  1/453 (0.22%)  0/452 (0.00%) 
Disease progression * 1  12/453 (2.65%)  33/452 (7.30%) 
Pain * 1  0/453 (0.00%)  2/452 (0.44%) 
Death * 1  3/453 (0.66%)  7/452 (1.55%) 
Injection site reaction * 1  0/453 (0.00%)  1/452 (0.22%) 
Infusion site extravasation * 1  0/453 (0.00%)  1/452 (0.22%) 
Sudden death * 1  1/453 (0.22%)  3/452 (0.66%) 
General physical health deterioration * 1  0/453 (0.00%)  1/452 (0.22%) 
Granuloma * 1  1/453 (0.22%)  0/452 (0.00%) 
Multi-organ failure * 1  0/453 (0.00%)  1/452 (0.22%) 
Hepatobiliary disorders     
Cholecystitis acute * 1  0/453 (0.00%)  1/452 (0.22%) 
Hepatomegaly * 1  0/453 (0.00%)  1/452 (0.22%) 
Immune system disorders     
Hypersensitivity * 1  0/453 (0.00%)  1/452 (0.22%) 
Drug hypersensitivity * 1  0/453 (0.00%)  1/452 (0.22%) 
Infections and infestations     
Pneumonia * 1  20/453 (4.42%)  15/452 (3.32%) 
Urinary tract infection * 1  1/453 (0.22%)  0/452 (0.00%) 
Bronchitis * 1  1/453 (0.22%)  4/452 (0.88%) 
Neutropenic infection * 1  11/453 (2.43%)  11/452 (2.43%) 
Respiratory tract infection * 1  7/453 (1.55%)  4/452 (0.88%) 
Upper respiratory tract infection * 1  0/453 (0.00%)  1/452 (0.22%) 
Lower respiratory tract infection * 1  3/453 (0.66%)  2/452 (0.44%) 
Neutropenic sepsis * 1  3/453 (0.66%)  10/452 (2.21%) 
Lung infection * 1  1/453 (0.22%)  1/452 (0.22%) 
Cellulitis * 1  0/453 (0.00%)  1/452 (0.22%) 
Anal abscess * 1  0/453 (0.00%)  1/452 (0.22%) 
Gastroenteritis * 1  0/453 (0.00%)  1/452 (0.22%) 
Pneumonia necrotising * 1  0/453 (0.00%)  2/452 (0.44%) 
Sepsis * 1  1/453 (0.22%)  2/452 (0.44%) 
Empyema * 1  1/453 (0.22%)  1/452 (0.22%) 
Groin abscess * 1  0/453 (0.00%)  1/452 (0.22%) 
Hepatitis c * 1  2/453 (0.44%)  0/452 (0.00%) 
Lobar pneumonia * 1  1/453 (0.22%)  1/452 (0.22%) 
Lung abscess * 1  0/453 (0.00%)  2/452 (0.44%) 
Skin infection * 1  0/453 (0.00%)  1/452 (0.22%) 
Abscess limb * 1  0/453 (0.00%)  1/452 (0.22%) 
Diverticulitis * 1  0/453 (0.00%)  1/452 (0.22%) 
Gastroenteritis viral * 1  0/453 (0.00%)  1/452 (0.22%) 
Infected skin ulcer * 1  0/453 (0.00%)  1/452 (0.22%) 
Lower respiratory tract infection bacterial * 1  1/453 (0.22%)  0/452 (0.00%) 
Perineal abscess * 1  0/453 (0.00%)  1/452 (0.22%) 
Pneumonia moraxella * 1  1/453 (0.22%)  0/452 (0.00%) 
Pneumonia staphylococcal * 1  0/453 (0.00%)  1/452 (0.22%) 
Pulmonary tuberculosis * 1  1/453 (0.22%)  0/452 (0.00%) 
Septic shock * 1  1/453 (0.22%)  0/452 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  1/453 (0.22%)  0/452 (0.00%) 
Accidental overdose * 1  0/453 (0.00%)  1/452 (0.22%) 
Toxicity to various agents * 1  0/453 (0.00%)  1/452 (0.22%) 
Infusion related reaction * 1  1/453 (0.22%)  0/452 (0.00%) 
Post procedural haemorrhage * 1  0/453 (0.00%)  1/452 (0.22%) 
Transfusion reaction * 1  1/453 (0.22%)  0/452 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/453 (0.44%)  3/452 (0.66%) 
Dehydration * 1  1/453 (0.22%)  6/452 (1.33%) 
Diabetes mellitus * 1  1/453 (0.22%)  0/452 (0.00%) 
Cachexia * 1  0/453 (0.00%)  1/452 (0.22%) 
Diabetes mellitus inadequate control * 1  0/453 (0.00%)  1/452 (0.22%) 
Hyperkalaemia * 1  0/453 (0.00%)  2/452 (0.44%) 
Hyponatraemia * 1  0/453 (0.00%)  2/452 (0.44%) 
Malnutrition * 1  0/453 (0.00%)  1/452 (0.22%) 
Hyperglycaemia * 1  1/453 (0.22%)  0/452 (0.00%) 
Hypokalaemia * 1  1/453 (0.22%)  0/452 (0.00%) 
Musculoskeletal and connective tissue disorders     
Bone pain * 1  0/453 (0.00%)  2/452 (0.44%) 
Pain in extremity * 1  0/453 (0.00%)  1/452 (0.22%) 
Musculoskeletal pain * 1  0/453 (0.00%)  1/452 (0.22%) 
Muscle spasms * 1  1/453 (0.22%)  0/452 (0.00%) 
Neck pain * 1  0/453 (0.00%)  1/452 (0.22%) 
Hypercreatinaemia * 1  1/453 (0.22%)  0/452 (0.00%) 
Myositis * 1  1/453 (0.22%)  0/452 (0.00%) 
Osteonecrosis of jaw * 1  0/453 (0.00%)  1/452 (0.22%) 
Pathological fracture * 1  0/453 (0.00%)  1/452 (0.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour pain * 1  0/453 (0.00%)  1/452 (0.22%) 
Cancer pain * 1  0/453 (0.00%)  1/452 (0.22%) 
Malignant pleural effusion * 1  2/453 (0.44%)  0/452 (0.00%) 
Colon cancer * 1  0/453 (0.00%)  1/452 (0.22%) 
Gastric cancer * 1  0/453 (0.00%)  1/452 (0.22%) 
Lymphangiosis carcinomatosa * 1  0/453 (0.00%)  1/452 (0.22%) 
Metastases to central nervous system * 1  1/453 (0.22%)  0/452 (0.00%) 
Metastases to meninges * 1  0/453 (0.00%)  1/452 (0.22%) 
Metastatic pain * 1  1/453 (0.22%)  0/452 (0.00%) 
Nervous system disorders     
Peripheral sensory neuropathy * 1  1/453 (0.22%)  0/452 (0.00%) 
Paraesthesia * 1  0/453 (0.00%)  1/452 (0.22%) 
Presyncope * 1  0/453 (0.00%)  1/452 (0.22%) 
Convulsion * 1  0/453 (0.00%)  3/452 (0.66%) 
Hypotonia * 1  0/453 (0.00%)  1/452 (0.22%) 
Hemiparesis * 1  0/453 (0.00%)  1/452 (0.22%) 
Transient ischaemic attack * 1  1/453 (0.22%)  1/452 (0.22%) 
Cerebral artery thrombosis * 1  1/453 (0.22%)  0/452 (0.00%) 
Depressed level of consciousness * 1  0/453 (0.00%)  1/452 (0.22%) 
Epilepsy * 1  0/453 (0.00%)  1/452 (0.22%) 
Facial paresis * 1  0/453 (0.00%)  1/452 (0.22%) 
Hemiplegia * 1  1/453 (0.22%)  0/452 (0.00%) 
Intracranial pressure increased * 1  1/453 (0.22%)  0/452 (0.00%) 
Ischaemic stroke * 1  1/453 (0.22%)  0/452 (0.00%) 
Subarachnoid haemorrhage * 1  0/453 (0.00%)  1/452 (0.22%) 
Psychiatric disorders     
Depression * 1  1/453 (0.22%)  0/452 (0.00%) 
Confusional state * 1  1/453 (0.22%)  6/452 (1.33%) 
Mental status changes * 1  1/453 (0.22%)  1/452 (0.22%) 
Delirium * 1  1/453 (0.22%)  0/452 (0.00%) 
Abnormal behaviour * 1  0/453 (0.00%)  1/452 (0.22%) 
Completed suicide * 1  1/453 (0.22%)  0/452 (0.00%) 
Renal and urinary disorders     
Proteinuria * 1  0/453 (0.00%)  1/452 (0.22%) 
Haematuria * 1  1/453 (0.22%)  0/452 (0.00%) 
Renal failure acute * 1  2/453 (0.44%)  0/452 (0.00%) 
Nephrotic syndrome * 1  0/453 (0.00%)  1/452 (0.22%) 
Renal impairment * 1  0/453 (0.00%)  2/452 (0.44%) 
Renal failure * 1  0/453 (0.00%)  1/452 (0.22%) 
Reproductive system and breast disorders     
Scrotal ulcer * 1  0/453 (0.00%)  1/452 (0.22%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  1/453 (0.22%)  0/452 (0.00%) 
Dyspnoea * 1  14/453 (3.09%)  13/452 (2.88%) 
Epistaxis * 1  0/453 (0.00%)  6/452 (1.33%) 
Haemoptysis * 1  3/453 (0.66%)  4/452 (0.88%) 
Productive cough * 1  1/453 (0.22%)  0/452 (0.00%) 
Pulmonary embolism * 1  8/453 (1.77%)  8/452 (1.77%) 
Dyspnoea exertional * 1  2/453 (0.44%)  0/452 (0.00%) 
Pleural effusion * 1  8/453 (1.77%)  2/452 (0.44%) 
Chronic obstructive pulmonary disease * 1  6/453 (1.32%)  1/452 (0.22%) 
Pneumothorax * 1  2/453 (0.44%)  6/452 (1.33%) 
Pneumonitis * 1  1/453 (0.22%)  1/452 (0.22%) 
Pulmonary haemorrhage * 1  0/453 (0.00%)  1/452 (0.22%) 
Pulmonary oedema * 1  0/453 (0.00%)  1/452 (0.22%) 
Acute respiratory failure * 1  2/453 (0.44%)  0/452 (0.00%) 
Hypoxia * 1  0/453 (0.00%)  1/452 (0.22%) 
Respiratory failure * 1  1/453 (0.22%)  1/452 (0.22%) 
Acquired tracheo-oesophageal fistula * 1  0/453 (0.00%)  1/452 (0.22%) 
Bronchiectasis * 1  1/453 (0.22%)  0/452 (0.00%) 
Bronchostenosis * 1  1/453 (0.22%)  0/452 (0.00%) 
Haemothorax * 1  1/453 (0.22%)  0/452 (0.00%) 
Pneumonia aspiration * 1  0/453 (0.00%)  1/452 (0.22%) 
Pulmonary artery thrombosis * 1  0/453 (0.00%)  1/452 (0.22%) 
Upper respiratory tract inflammation * 1  1/453 (0.22%)  0/452 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash * 1  0/453 (0.00%)  1/452 (0.22%) 
Subcutaneous emphysema * 1  0/453 (0.00%)  1/452 (0.22%) 
Hyperkeratosis * 1  0/453 (0.00%)  1/452 (0.22%) 
Vascular disorders     
Hypertension * 1  0/453 (0.00%)  1/452 (0.22%) 
Phlebitis superficial * 1  0/453 (0.00%)  1/452 (0.22%) 
Deep vein thrombosis * 1  2/453 (0.44%)  1/452 (0.22%) 
Thrombophlebitis superficial * 1  1/453 (0.22%)  0/452 (0.00%) 
Subclavian vein thrombosis * 1  2/453 (0.44%)  0/452 (0.00%) 
Orthostatic hypotension * 1  0/453 (0.00%)  1/452 (0.22%) 
Arterial stenosis * 1  1/453 (0.22%)  0/452 (0.00%) 
Embolism venous * 1  1/453 (0.22%)  0/452 (0.00%) 
Jugular vein thrombosis * 1  0/453 (0.00%)  1/452 (0.22%) 
Peripheral ischaemia * 1  0/453 (0.00%)  1/452 (0.22%) 
*
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/Docetaxel Aflibercept/Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   388/453 (85.65%)   402/452 (88.94%) 
Eye disorders     
Lacrimation increased * 1  18/453 (3.97%)  41/452 (9.07%) 
Gastrointestinal disorders     
Stomatitis * 1  69/453 (15.23%)  180/452 (39.82%) 
Diarrhoea * 1  106/453 (23.40%)  124/452 (27.43%) 
Nausea * 1  92/453 (20.31%)  79/452 (17.48%) 
Constipation * 1  55/453 (12.14%)  65/452 (14.38%) 
Vomiting * 1  56/453 (12.36%)  57/452 (12.61%) 
Abdominal pain * 1  25/453 (5.52%)  20/452 (4.42%) 
Dysphagia * 1  6/453 (1.32%)  23/452 (5.09%) 
General disorders     
Fatigue * 1  130/453 (28.70%)  142/452 (31.42%) 
Asthenia * 1  84/453 (18.54%)  83/452 (18.36%) 
Pyrexia * 1  42/453 (9.27%)  53/452 (11.73%) 
Oedema peripheral * 1  54/453 (11.92%)  29/452 (6.42%) 
Non-cardiac chest pain * 1  29/453 (6.40%)  32/452 (7.08%) 
Investigations     
Weight decreased * 1  35/453 (7.73%)  110/452 (24.34%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  93/453 (20.53%)  122/452 (26.99%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  29/453 (6.40%)  43/452 (9.51%) 
Myalgia * 1  31/453 (6.84%)  38/452 (8.41%) 
Arthralgia * 1  36/453 (7.95%)  31/452 (6.86%) 
Bone pain * 1  22/453 (4.86%)  27/452 (5.97%) 
Pain in extremity * 1  25/453 (5.52%)  20/452 (4.42%) 
Musculoskeletal pain * 1  24/453 (5.30%)  19/452 (4.20%) 
Nervous system disorders     
Peripheral sensory neuropathy * 1  65/453 (14.35%)  54/452 (11.95%) 
Headache * 1  27/453 (5.96%)  59/452 (13.05%) 
Dysgeusia * 1  15/453 (3.31%)  35/452 (7.74%) 
Paraesthesia * 1  27/453 (5.96%)  20/452 (4.42%) 
Renal and urinary disorders     
Proteinuria * 1  4/453 (0.88%)  34/452 (7.52%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  94/453 (20.75%)  108/452 (23.89%) 
Dyspnoea * 1  89/453 (19.65%)  85/452 (18.81%) 
Epistaxis * 1  28/453 (6.18%)  90/452 (19.91%) 
Dysphonia * 1  16/453 (3.53%)  83/452 (18.36%) 
Haemoptysis * 1  23/453 (5.08%)  24/452 (5.31%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  148/453 (32.67%)  133/452 (29.42%) 
Nail disorder * 1  33/453 (7.28%)  42/452 (9.29%) 
Rash * 1  26/453 (5.74%)  30/452 (6.64%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  6/453 (1.32%)  28/452 (6.19%) 
Vascular disorders     
Hypertension * 1  23/453 (5.08%)  95/452 (21.02%) 
*
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 30 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 90 days).
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi-aventis
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00532155     History of Changes
Other Study ID Numbers: EFC10261
EudraCT 2007-000819-29
First Submitted: September 19, 2007
First Posted: September 20, 2007
Results First Submitted: August 17, 2012
Results First Posted: January 1, 2013
Last Update Posted: June 7, 2016