Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 66 of 78 for:    sanofi-aventis and sweden

Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer (VENICE)

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: NCT00519285
Recruitment Status : Completed
First Posted : August 22, 2007
Results First Posted : October 10, 2013
Last Update Posted : July 22, 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 Prostatic Neoplasms
Neoplasm Metastasis
Interventions Drug: Aflibercept
Drug: Placebo (for aflibercept)
Drug: Docetaxel
Drug: Prednisone or Prednisolone
Enrollment 1224
Recruitment Details Between August 2007 and February 2010, a total of 1548 patients gave informed consent for this study.
Pre-assignment Details Amongst these patients, a total of 324 were screening failures (primarily due to non-compliance with exclusion criteria) and did not get randomized.
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Period Title: Overall Study
Started 612 [1] 612 [1]
TREATED 604 [2] 605 [3]
Still Treated at Cut-off Date 1 [4] 2
Completed 0 [5] 0
Not Completed 612 612
Reason Not Completed
Adverse Event             127             266
Disease progression             334             186
Physician Decision             75             47
Participant's request             53             84
Consent withdrawn             4             5
Poor compliance to protocol             5             7
Reason unspecified             5             8
Not treated             8             7
Treatment ongoing             1             2
[1]
Randomized
[2]
Received at least part of one dose of placebo
[3]
Received at least part of one dose of aflibercept
[4]
The cut-off date for analysis was defined as 07 February 2012, date at which 873 deaths has occurred
[5]
Participants were treated until progressive disease, unacceptable toxicity, or refusal of treatment
Arm/Group Title Placebo Aflibercept Total
Hide Arm/Group Description Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily Total of all reporting groups
Overall Number of Baseline Participants 612 612 1224
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 612 participants 612 participants 1224 participants
67.6  (8.0) 67.9  (7.8) 67.8  (7.9)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 612 participants 612 participants 1224 participants
<65 years 225 195 420
65-74 years 259 283 542
≥75 years 128 134 262
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Male Number Analyzed 612 participants 612 participants 1224 participants
612 612 1224
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 612 participants 612 participants 1224 participants
Caucasian/White 552 560 1112
Black 17 15 32
Asian/Oriental 36 32 68
Other 7 5 12
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 612 participants 612 participants 1224 participants
Western Europe 219 227 446
Eastern Europe 131 132 263
North America 81 95 176
South America 88 71 159
Other region 93 87 180
Body Surface Area (BSA)  
Mean (Standard Deviation)
Unit of measure:  M²
Number Analyzed 612 participants 612 participants 1224 participants
2.0  (0.2) 2.0  (0.2) 2.0  (0.2)
Eastern Co-operative Group (ECOG) performance status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 612 participants 612 participants 1224 participants
ECOG 0 285 283 568
ECOG 1 299 303 602
ECOG 2 28 26 54
[1]
Measure Description:

ECOG performance status:

  • 0 = Fully active, able to carry on all pre-disease performance without restriction
  • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  • 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
1.Primary Outcome
Title Overall Survival Time
Hide Description

Overall survival (OS) time was measured as the time from date of randomization to the date of death due to any cause.

The median OS time and its 95.6% confidence interval were estimated using the Kaplan-Meier method. In the absence of confirmation of death, the participant was censored at the last date he/she was known to be alive or the study cut-off date (when 873 deaths have occurred), whichever was earlier.

Time Frame From randomization up to the cut-off date (median follow-up of 35.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the Intent-to-treat (ITT) population (i.e all randomized participants according to the treatment assigned regardless of the drug actually received).

At the cut-off date, 873 deaths had occurred, 445 in the Placebo group and 428 in the Aflibercept group.

Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 612 612
Median (95% Confidence Interval)
Unit of Measure: months
21.22
(19.614 to 23.754)
22.14
(20.304 to 24.082)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Aflibercept
Comments

Null hypothesis: No difference between aflibercept and placebo

The study was designed to provide 90% power to detect a 1.25-fold increase in median survival with aflibercept compared to placebo at a overall one-sided significance level of 0.025 with 873 deaths.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3802
Comments A priori threshold for statistical significance was set to 0.044 using the O'Brien-Fleming alpha spending function to account for two interim analyses.
Method Log Rank
Comments Log rank test stratified on ECOG Performance Status
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.942
Confidence Interval (2-Sided) 95.6%
0.822 to 1.08
Estimation Comments Hazard ratio (HR) aflibercept versus placebo estimated from a Cox proportional hazard model stratified on ECOG Performance Status
2.Secondary Outcome
Title Prostate Specific Antigen Response Rate
Hide Description Prostate specific antigen (PSA) response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response.
Time Frame Before randomization (baseline) then every 3 weeks up to PSA progression (≥25% increase) or the cut-off date, whichever occurred first
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the ITT population evaluable for PSA response (i.e. with a baseline PSA ≥10 ng/mL).
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 559 560
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
63.5
(59.5 to 67.5)
68.6
(64.7 to 72.4)
3.Secondary Outcome
Title Time to Skeletal Related Events
Hide Description

Skeletal Related Events (SRE) included pathological fractures and/or spinal cord compression, need for bone irradiation, including radioisotopes or bone surgery, change in antineoplastic therapy to treat bone pain.

Time to SRE was defined as the time from the date of randomization to the date of occurence of the first event defining a SRE or death due to any cause, whichever occurred first.

The median time to SRE and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of SRE, the participant was censored at the last date he/she was known to be alive or the study cut-off date, whichever was earlier.

Time Frame From randomization up to the cut-off date (median follow-up of 35.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the ITT population.

At the cut-off date, SRE or death had occurred in 1013 participants, 516 in the Placebo group and 497 in the Aflibercept group.

Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 612 612
Median (95% Confidence Interval)
Unit of Measure: months
14.98
(13.733 to 16.427)
15.31
(14.127 to 16.657)
4.Secondary Outcome
Title Progression Free Survival Time
Hide Description

Disease progression was defined as a composite of: Radiological tumor progression (≥20% increase in target lesions, or appearance of at least 2 new bone lesions); PSA progression (≥25% increase in PSA level confirmed 3 weeks later); Pain progression (increase in pain intensity or in analgesic consumption for cancer related pain confirmed 3 weeks later); Radiotherapy for cancer related symptoms; Occurence of Skeletal related events (SRE).

Progression Free survival (PFS) time was measured as the time from the date of randomization up to the date of occurrence of the first event defining a disease progression or death due to any cause, whichever occurred first.

The median PFS time and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of disease progression, the participant was censored at the the date of last assessment without evidence of progression or the study cut-off date, whichever was earlier.

Time Frame From randomization up to the cut-off date (median follow-up of 35.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the ITT population.

At the cut-off date, disease progression or death had occurred in 1184 participants, 592 in each treatment group.

Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 612 612
Median (95% Confidence Interval)
Unit of Measure: months
6.24
(5.585 to 6.899)
6.90
(6.209 to 7.359)
5.Secondary Outcome
Title Tumor Response Rate in Participants With Measurable Disease
Hide Description Tumor response was defined as either a Complete Response (disappearance of all target lesions) or a Partial Response (≥30% decrease from baseline in target lesions) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST)version 1.0.
Time Frame Before randomization (baseline) then every 3 months up to tumor progression (≥25% increase) or the cut-off date, whichever occurred first
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the ITT population evaluable for tumor response (i.e. received at least one dose of study drugs (aflibercept/placebo or docetaxel), had no important deviations to protocol and was evaluable for response as per RECIST version 1.0).
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 320 323
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.1
(23.2 to 33.1)
38.7
(33.4 to 44.0)
6.Secondary Outcome
Title Prostate Specific Antigen Progression-free Survival Time
Hide Description

Prostate specific antigen (PSA) progression was defined as ≥25% increase in PSA level confirmed 3 weeks later, above the nadir in participants who had achieved a PSA response, or above the baseline in participants who hadn't achieved a PSA response.

PSA progression-free survival (PFS) time was defined as the time from the date of randomization up to the date of the first documented PSA progression or death due to any cause, whichever occurred first.

The median PSA-PFS time and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of PSA progression or death, the participant was censored at the the date of last assessment without evidence of progression or the study cut-off date, whichever was earlier.

Time Frame From randomization up to the cut-off date (median follow-up of 35.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed in the ITT population evaluable for PSA progression (i.e. with an evaluable baseline PSA).

At the cut-off date, PSA progression or death had occurred in 1138 participants, 571 in the Placebo group and 567 in the Aflibercept group.

Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 606 608
Median (95% Confidence Interval)
Unit of Measure: months
8.11
(7.622 to 8.575)
8.25
(7.819 to 8.772)
7.Secondary Outcome
Title Pain Progression-free Survival Time
Hide Description

Pain progression was defined as either ≥1-point increase in Present Pain Intensity (PPI) score or ≥25% increase in Analgesics Score (AS) confirmed at least 3 weeks later, or requirement for palliative radiotherapy. PPI scale is a self-report 0-5 scale to assess pain intensity - a score 0 reflects no pain, a score 5 reflects excruciating pain. AS is a scoring method to assess analgesics consumption. Each analgesic is scored 1 or 4 depending on the analgesic type and dose. AS is the sum of the analgesic scores.

Pain progression-free survival (PFS) time was measured as the time from the date of randomization up to the date of first pain progression or death due to any cause, whichever occurred first.

The median pain-PFS and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of event, the participant was censored at the the date of last assessment without evidence of pain progression or the study cut-off date, whichever was earlier.

Time Frame From randomization up to the cut-off date (median follow-up of 35.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the ITT population evaluable for pain progression (i.e. with no pain or with stable pain at baseline).

At the cut-off date, pain progression or death had occurred in 507 participants, 263 in the Placebo group and 244 in the Aflibercept group.

Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 301 287
Median (95% Confidence Interval)
Unit of Measure: months
9.72
(8.509 to 11.499)
9.20
(8.181 to 10.448)
8.Secondary Outcome
Title Pain Response Rate
Hide Description Pain response was defined as either a ≥2-point decrease from baseline in Present Pain Intensity (PPI) score without increase in Analgesics Score (AS), or a ≥50% decrease from baseline in AS without increase in the PPI score confirmed at least 3 weeks later. Increases in PPI or AS during the first 12 weeks were ignored in determining pain response.
Time Frame Before randomization (baseline) then every 3 weeks up to pain progression or the cut-off date, whichever occurred first
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in the ITT population evaluable for pain response (i.e. stable analgesia at baseline and, baseline PPI ≥2 and/or baseline AS ≥10 points).
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 67 67
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
46.3
(34.3 to 58.2)
35.8
(24.3 to 47.3)
9.Secondary Outcome
Title Change From Baseline in Functional Assessment of Cancer Therapy-Prostate Total Score as a Measure of Health Related Quality of Life
Hide Description

Functional Assessment of Cancer Therapy-Prostate (FACT-P) is a 39-item participant questionnaire that measures the concerns of patients with prostate cancer. It consists of 5 subscales assessing physical well-being, social/family well-being, emotional well-being, functional well-being, and prostate-specific concerns.

FACT-P total score is the sum of the 5 subscores. It ranges from 0 to 156 with higher score indicating better quality of life.

Time Frame Before randomization (baseline) then every 3 weeks until disease progression or administration of further antitumor therapy, whichever came first
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the ITT population evaluable for Health related quality of life (i.e. with baseline and at least one post-baseline evaluable FACT-P questionnaire).
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 574 568
Mean (Standard Deviation)
Unit of Measure: units on a scale
Change from baseline at cycle 1 (n =493, 461) 5.08  (12.73) 1.30  (15.70)
Change from baseline at cycle 2 (n =467, 437) 6.22  (14.50) -0.03  (17.99)
Change from baseline at cycle 6 (n =293, 224) 5.50  (16.38) -1.00  (16.85)
Change from baseline at cycle 10 (n =158, 117) 6.61  (16.35) -1.60  (15.41)
10.Secondary Outcome
Title Number of Participants With Adverse Events as a Measure of Safety
Hide Description

Adverse Events (AE) are any unfavorable and unintended sign, symptom, syndrome or illness observed by the investigator or reported by the participant during the study.

AE were collected at regular intervals throughout the study then graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.3.0).

Time Frame From first dose of study treatment (aflibercept/placebo or docetaxel whichever came first) to last dose of study treatment (aflibercept/placebo or docetaxel whichever came last) + 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the safety population (i.e. all randomized and treated participants according to the treatment actually received). Six participants in the Placebo group who received at least one dose of aflibercept in error were considered in the Aflibercept group.
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 598 611
Measure Type: Number
Unit of Measure: participants
Any Adverse Event 585 607
- Grade 3-4 AE 290 470
- Serious AE 184 331
- AE leading to death 23 46
--- Related AE leading to death 8 19
- AE leading to permanent discontinuation 125 268
- AE leading to premature discontinuation 73 116
11.Secondary Outcome
Title Number of Participants With Positive Anti-aflibercept Antibody Levels as a Measure of Immunogenicity of Aflibercept
Hide Description

Serum for detection of anti-drug antibodies (ADA) was collected in patients treated in selected centers only. Samples were analyzed using a titer-based, bridging immunoassay developed and validated to detect ADAs in human serum.

Samples with positive antibody levels were further analyzed using a validated, non-quantitative ligand binding assay to detect neutralizing antibodies Ab).

A participant was considered to have positive antibody levels if antibodies were detected above the quantification limits.

Time Frame Pre-dose of cycle 1 (baseline), pre-dose of each every other cycle, then 30 and 90 days after the last administration of the study drug
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the safety population evaluable for immunogenicity (i.e. exposed to aflibercept with serum samples evaluable for immunogenicity).
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description:
Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Overall Number of Participants Analyzed 149 179
Measure Type: Number
Unit of Measure: participants
At baseline 0 2
At any time post-baseline 4 9
- Neutralizing Ab 0 2
- Not neutralizing Ab 2 5
- Neutralizing potential not evaluated 2 2
Time Frame Adverse Events (AE) were collected from signature of the informed consent form up to the last visit in the study.
Adverse Event Reporting Description The analysis was performed on the safety population as described for Outcome measure 10 (i.e. according to the treatment actually received) and included all AE that developed or worsened from first dose of aflibercept/placebo or docetaxel whichever came first, to 30 days after last dose of aflibercept/placebo or docetaxel whichever came last.
 
Arm/Group Title Placebo Aflibercept
Hide Arm/Group Description Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
All-Cause Mortality
Placebo Aflibercept
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Aflibercept
Affected / at Risk (%) Affected / at Risk (%)
Total   184/598 (30.77%)   331/611 (54.17%) 
Blood and lymphatic system disorders     
Febrile neutropenia * 1  21/598 (3.51%)  48/611 (7.86%) 
Neutropenia * 1  8/598 (1.34%)  30/611 (4.91%) 
Anaemia * 1  3/598 (0.50%)  2/611 (0.33%) 
Thrombocytopenia * 1  0/598 (0.00%)  1/611 (0.16%) 
Thrombotic microangiopathy * 1  0/598 (0.00%)  2/611 (0.33%) 
Leukopenia * 1  1/598 (0.17%)  1/611 (0.16%) 
Normochromic normocytic anaemia * 1  1/598 (0.17%)  0/611 (0.00%) 
Pancytopenia * 1  0/598 (0.00%)  1/611 (0.16%) 
Cardiac disorders     
Atrial fibrillation * 1  3/598 (0.50%)  7/611 (1.15%) 
Palpitations * 1  0/598 (0.00%)  1/611 (0.16%) 
Sinus tachycardia * 1  0/598 (0.00%)  1/611 (0.16%) 
Angina pectoris * 1  0/598 (0.00%)  1/611 (0.16%) 
Acute myocardial infarction * 1  5/598 (0.84%)  0/611 (0.00%) 
Supraventricular tachycardia * 1  0/598 (0.00%)  1/611 (0.16%) 
Myocardial infarction * 1  2/598 (0.33%)  1/611 (0.16%) 
Left ventricular dysfunction * 1  1/598 (0.17%)  0/611 (0.00%) 
Myocardial ischaemia * 1  2/598 (0.33%)  0/611 (0.00%) 
Ventricular extrasystoles * 1  0/598 (0.00%)  1/611 (0.16%) 
Angina unstable * 1  0/598 (0.00%)  1/611 (0.16%) 
Atrioventricular block complete * 1  1/598 (0.17%)  0/611 (0.00%) 
Cardiac arrest * 1  1/598 (0.17%)  0/611 (0.00%) 
Coronary artery stenosis * 1  1/598 (0.17%)  0/611 (0.00%) 
Left ventricular failure * 1  0/598 (0.00%)  1/611 (0.16%) 
Mitral valve incompetence * 1  0/598 (0.00%)  1/611 (0.16%) 
Restrictive cardiomyopathy * 1  0/598 (0.00%)  1/611 (0.16%) 
Tachycardia paroxysmal * 1  1/598 (0.17%)  0/611 (0.00%) 
Ventricular fibrillation * 1  0/598 (0.00%)  1/611 (0.16%) 
Endocrine disorders     
Hyperthyroidism * 1  0/598 (0.00%)  1/611 (0.16%) 
Eye disorders     
Corneal erosion * 1  0/598 (0.00%)  1/611 (0.16%) 
Pigmentary glaucoma * 1  0/598 (0.00%)  1/611 (0.16%) 
Gastrointestinal disorders     
Diarrhoea * 1  11/598 (1.84%)  17/611 (2.78%) 
Stomatitis * 1  1/598 (0.17%)  14/611 (2.29%) 
Nausea * 1  1/598 (0.17%)  1/611 (0.16%) 
Constipation * 1  3/598 (0.50%)  3/611 (0.49%) 
Vomiting * 1  3/598 (0.50%)  5/611 (0.82%) 
Abdominal pain * 1  1/598 (0.17%)  2/611 (0.33%) 
Abdominal pain upper * 1  0/598 (0.00%)  1/611 (0.16%) 
Rectal haemorrhage * 1  0/598 (0.00%)  4/611 (0.65%) 
Dysphagia * 1  0/598 (0.00%)  1/611 (0.16%) 
Anal fistula * 1  0/598 (0.00%)  5/611 (0.82%) 
Haematochezia * 1  1/598 (0.17%)  0/611 (0.00%) 
Oesophagitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Anal fissure * 1  0/598 (0.00%)  3/611 (0.49%) 
Gastritis * 1  0/598 (0.00%)  1/611 (0.16%) 
Gastric ulcer * 1  0/598 (0.00%)  2/611 (0.33%) 
Gastrointestinal haemorrhage * 1  3/598 (0.50%)  3/611 (0.49%) 
Intestinal perforation * 1  0/598 (0.00%)  7/611 (1.15%) 
Anal inflammation * 1  1/598 (0.17%)  0/611 (0.00%) 
Diverticular perforation * 1  0/598 (0.00%)  5/611 (0.82%) 
Lower gastrointestinal haemorrhage * 1  1/598 (0.17%)  3/611 (0.49%) 
Ileus * 1  0/598 (0.00%)  2/611 (0.33%) 
Rectal ulcer * 1  1/598 (0.17%)  3/611 (0.49%) 
Colitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Duodenal ulcer * 1  0/598 (0.00%)  2/611 (0.33%) 
Gastrointestinal inflammation * 1  0/598 (0.00%)  2/611 (0.33%) 
Oesophageal ulcer * 1  0/598 (0.00%)  3/611 (0.49%) 
Peptic ulcer * 1  0/598 (0.00%)  2/611 (0.33%) 
Upper gastrointestinal haemorrhage * 1  1/598 (0.17%)  2/611 (0.33%) 
Colitis ischaemic * 1  0/598 (0.00%)  2/611 (0.33%) 
Diverticulum intestinal * 1  0/598 (0.00%)  1/611 (0.16%) 
Duodenal ulcer perforation * 1  1/598 (0.17%)  1/611 (0.16%) 
Enteritis * 1  0/598 (0.00%)  1/611 (0.16%) 
Enterovesical fistula * 1  0/598 (0.00%)  2/611 (0.33%) 
Gastritis erosive * 1  0/598 (0.00%)  1/611 (0.16%) 
Duodenal ulcer haemorrhage * 1  0/598 (0.00%)  1/611 (0.16%) 
Faecalith * 1  0/598 (0.00%)  1/611 (0.16%) 
Gastric haemorrhage * 1  0/598 (0.00%)  1/611 (0.16%) 
Gastric ulcer haemorrhage * 1  0/598 (0.00%)  1/611 (0.16%) 
Gastrointestinal tract mucosal discolouration * 1  0/598 (0.00%)  1/611 (0.16%) 
Ileus paralytic * 1  1/598 (0.17%)  0/611 (0.00%) 
Intestinal obstruction * 1  0/598 (0.00%)  1/611 (0.16%) 
Intestinal prolapse * 1  0/598 (0.00%)  1/611 (0.16%) 
Large intestine perforation * 1  0/598 (0.00%)  1/611 (0.16%) 
Mallory-weiss syndrome * 1  0/598 (0.00%)  1/611 (0.16%) 
Necrotising colitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Neutropenic colitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Omental infarction * 1  0/598 (0.00%)  1/611 (0.16%) 
Peptic ulcer perforation * 1  0/598 (0.00%)  1/611 (0.16%) 
Periproctitis * 1  1/598 (0.17%)  0/611 (0.00%) 
Pharyngoesophageal diverticulum * 1  0/598 (0.00%)  1/611 (0.16%) 
Pneumoperitoneum * 1  0/598 (0.00%)  1/611 (0.16%) 
Rectal ulcer haemorrhage * 1  0/598 (0.00%)  1/611 (0.16%) 
Small intestinal haemorrhage * 1  0/598 (0.00%)  1/611 (0.16%) 
General disorders     
Fatigue * 1  0/598 (0.00%)  5/611 (0.82%) 
Asthenia * 1  3/598 (0.50%)  6/611 (0.98%) 
Oedema peripheral * 1  1/598 (0.17%)  1/611 (0.16%) 
Pyrexia * 1  6/598 (1.00%)  8/611 (1.31%) 
Pain * 1  0/598 (0.00%)  1/611 (0.16%) 
Disease progression * 1  3/598 (0.50%)  10/611 (1.64%) 
Non-cardiac chest pain * 1  1/598 (0.17%)  1/611 (0.16%) 
Infusion site extravasation * 1  0/598 (0.00%)  1/611 (0.16%) 
Performance status decreased * 1  0/598 (0.00%)  1/611 (0.16%) 
General physical health deterioration * 1  0/598 (0.00%)  1/611 (0.16%) 
Impaired healing * 1  0/598 (0.00%)  1/611 (0.16%) 
Death * 1  1/598 (0.17%)  2/611 (0.33%) 
Injection site reaction * 1  1/598 (0.17%)  0/611 (0.00%) 
Multi-organ failure * 1  1/598 (0.17%)  1/611 (0.16%) 
Sudden death * 1  0/598 (0.00%)  2/611 (0.33%) 
Sudden cardiac death * 1  0/598 (0.00%)  1/611 (0.16%) 
Hepatobiliary disorders     
Bile duct obstruction * 1  0/598 (0.00%)  1/611 (0.16%) 
Hepatitis * 1  1/598 (0.17%)  0/611 (0.00%) 
Immune system disorders     
Hypersensitivity * 1  1/598 (0.17%)  3/611 (0.49%) 
Drug hypersensitivity * 1  1/598 (0.17%)  3/611 (0.49%) 
Anaphylactic reaction * 1  1/598 (0.17%)  0/611 (0.00%) 
Infections and infestations     
Urinary tract infection * 1  4/598 (0.67%)  10/611 (1.64%) 
Upper respiratory tract infection * 1  2/598 (0.33%)  1/611 (0.16%) 
Pneumonia * 1  11/598 (1.84%)  21/611 (3.44%) 
Neutropenic infection * 1  12/598 (2.01%)  22/611 (3.60%) 
Bronchitis * 1  1/598 (0.17%)  2/611 (0.33%) 
Oral candidiasis * 1  0/598 (0.00%)  1/611 (0.16%) 
Pharyngitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Anal abscess * 1  0/598 (0.00%)  13/611 (2.13%) 
Herpes zoster * 1  0/598 (0.00%)  1/611 (0.16%) 
Lower respiratory tract infection * 1  2/598 (0.33%)  0/611 (0.00%) 
Respiratory tract infection * 1  1/598 (0.17%)  1/611 (0.16%) 
Cystitis * 1  1/598 (0.17%)  0/611 (0.00%) 
Cellulitis * 1  1/598 (0.17%)  1/611 (0.16%) 
Localised infection * 1  0/598 (0.00%)  1/611 (0.16%) 
Neutropenic sepsis * 1  3/598 (0.50%)  7/611 (1.15%) 
Sepsis * 1  2/598 (0.33%)  4/611 (0.65%) 
Gastroenteritis * 1  0/598 (0.00%)  1/611 (0.16%) 
Diverticulitis * 1  0/598 (0.00%)  4/611 (0.65%) 
Skin infection * 1  1/598 (0.17%)  1/611 (0.16%) 
Bronchopneumonia * 1  1/598 (0.17%)  3/611 (0.49%) 
Device related infection * 1  0/598 (0.00%)  1/611 (0.16%) 
Escherichia urinary tract infection * 1  1/598 (0.17%)  0/611 (0.00%) 
Infection * 1  1/598 (0.17%)  2/611 (0.33%) 
Peridiverticular abscess * 1  0/598 (0.00%)  3/611 (0.49%) 
Rectal abscess * 1  0/598 (0.00%)  3/611 (0.49%) 
Abscess intestinal * 1  0/598 (0.00%)  2/611 (0.33%) 
Abscess limb * 1  1/598 (0.17%)  0/611 (0.00%) 
Anal infection * 1  0/598 (0.00%)  1/611 (0.16%) 
Erysipelas * 1  0/598 (0.00%)  2/611 (0.33%) 
Escherichia sepsis * 1  1/598 (0.17%)  1/611 (0.16%) 
Osteomyelitis * 1  1/598 (0.17%)  0/611 (0.00%) 
Pneumonia staphylococcal * 1  1/598 (0.17%)  1/611 (0.16%) 
Septic shock * 1  1/598 (0.17%)  2/611 (0.33%) 
Abdominal abscess * 1  1/598 (0.17%)  1/611 (0.16%) 
Bacteraemia * 1  1/598 (0.17%)  0/611 (0.00%) 
Gastroenteritis viral * 1  0/598 (0.00%)  1/611 (0.16%) 
Gastrointestinal infection * 1  1/598 (0.17%)  0/611 (0.00%) 
Lobar pneumonia * 1  1/598 (0.17%)  1/611 (0.16%) 
Lung infection * 1  1/598 (0.17%)  0/611 (0.00%) 
Nasal abscess * 1  1/598 (0.17%)  0/611 (0.00%) 
Necrotising fasciitis * 1  0/598 (0.00%)  2/611 (0.33%) 
Pulmonary tuberculosis * 1  0/598 (0.00%)  1/611 (0.16%) 
Pyonephrosis * 1  1/598 (0.17%)  1/611 (0.16%) 
Tracheobronchitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Abdominal infection * 1  0/598 (0.00%)  1/611 (0.16%) 
Appendicitis * 1  1/598 (0.17%)  0/611 (0.00%) 
Aspergillosis * 1  0/598 (0.00%)  1/611 (0.16%) 
Bronchiolitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Catheter site cellulitis * 1  1/598 (0.17%)  0/611 (0.00%) 
Cystitis bacterial * 1  1/598 (0.17%)  0/611 (0.00%) 
Cytomegalovirus hepatitis * 1  1/598 (0.17%)  0/611 (0.00%) 
Herpes oesophagitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Infected bites * 1  0/598 (0.00%)  1/611 (0.16%) 
Infectious peritonitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Listeria sepsis * 1  1/598 (0.17%)  0/611 (0.00%) 
Lung abscess * 1  1/598 (0.17%)  0/611 (0.00%) 
Perineal abscess * 1  1/598 (0.17%)  0/611 (0.00%) 
Perirectal abscess * 1  1/598 (0.17%)  0/611 (0.00%) 
Pneumonia bacterial * 1  0/598 (0.00%)  1/611 (0.16%) 
Pneumonia necrotising * 1  0/598 (0.00%)  1/611 (0.16%) 
Post procedural infection * 1  0/598 (0.00%)  1/611 (0.16%) 
Pulmonary sepsis * 1  1/598 (0.17%)  0/611 (0.00%) 
Pyelonephritis acute * 1  0/598 (0.00%)  1/611 (0.16%) 
Staphylococcal bacteraemia * 1  0/598 (0.00%)  1/611 (0.16%) 
Staphylococcal infection * 1  1/598 (0.17%)  0/611 (0.00%) 
Urosepsis * 1  1/598 (0.17%)  0/611 (0.00%) 
West nile viral infection * 1  1/598 (0.17%)  0/611 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  0/598 (0.00%)  1/611 (0.16%) 
Traumatic fracture * 1  1/598 (0.17%)  2/611 (0.33%) 
Gastroenteritis radiation * 1  0/598 (0.00%)  1/611 (0.16%) 
Abdominal wound dehiscence * 1  0/598 (0.00%)  2/611 (0.33%) 
Joint dislocation * 1  0/598 (0.00%)  1/611 (0.16%) 
Post procedural haemorrhage * 1  1/598 (0.17%)  0/611 (0.00%) 
Pelvic fracture * 1  1/598 (0.17%)  0/611 (0.00%) 
Pneumothorax traumatic * 1  0/598 (0.00%)  1/611 (0.16%) 
Procedural complication * 1  1/598 (0.17%)  0/611 (0.00%) 
Skull fracture * 1  1/598 (0.17%)  0/611 (0.00%) 
Upper limb fracture * 1  1/598 (0.17%)  0/611 (0.00%) 
Urinary bladder rupture * 1  0/598 (0.00%)  1/611 (0.16%) 
Investigations     
Haemoglobin decreased * 1  0/598 (0.00%)  2/611 (0.33%) 
Electrocardiogram t wave inversion * 1  0/598 (0.00%)  1/611 (0.16%) 
International normalised ratio increased * 1  0/598 (0.00%)  1/611 (0.16%) 
Electrocardiogram st-t segment abnormal * 1  0/598 (0.00%)  1/611 (0.16%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  0/598 (0.00%)  1/611 (0.16%) 
Dehydration * 1  2/598 (0.33%)  19/611 (3.11%) 
Hyperglycaemia * 1  2/598 (0.33%)  1/611 (0.16%) 
Hypoglycaemia * 1  1/598 (0.17%)  2/611 (0.33%) 
Diabetes mellitus inadequate control * 1  1/598 (0.17%)  0/611 (0.00%) 
Failure to thrive * 1  0/598 (0.00%)  2/611 (0.33%) 
Hypocalcaemia * 1  0/598 (0.00%)  2/611 (0.33%) 
Hyponatraemia * 1  0/598 (0.00%)  2/611 (0.33%) 
Hypernatraemia * 1  0/598 (0.00%)  1/611 (0.16%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  6/598 (1.00%)  0/611 (0.00%) 
Arthralgia * 1  1/598 (0.17%)  1/611 (0.16%) 
Bone pain * 1  1/598 (0.17%)  0/611 (0.00%) 
Muscular weakness * 1  2/598 (0.33%)  0/611 (0.00%) 
Pathological fracture * 1  3/598 (0.50%)  2/611 (0.33%) 
Osteonecrosis of jaw * 1  1/598 (0.17%)  1/611 (0.16%) 
Neck pain * 1  1/598 (0.17%)  0/611 (0.00%) 
Spinal osteoarthritis * 1  0/598 (0.00%)  1/611 (0.16%) 
Intervertebral disc protrusion * 1  1/598 (0.17%)  0/611 (0.00%) 
Osteoporotic fracture * 1  0/598 (0.00%)  1/611 (0.16%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastatic pain * 1  3/598 (0.50%)  0/611 (0.00%) 
Tumour pain * 1  1/598 (0.17%)  0/611 (0.00%) 
Colon cancer * 1  1/598 (0.17%)  2/611 (0.33%) 
Cardiac myxoma * 1  1/598 (0.17%)  0/611 (0.00%) 
Colorectal cancer * 1  0/598 (0.00%)  1/611 (0.16%) 
Lung neoplasm malignant * 1  1/598 (0.17%)  0/611 (0.00%) 
Meningioma * 1  0/598 (0.00%)  1/611 (0.16%) 
Metastases to bone * 1  1/598 (0.17%)  0/611 (0.00%) 
Pituitary tumour benign * 1  1/598 (0.17%)  0/611 (0.00%) 
Nervous system disorders     
Peripheral sensory neuropathy * 1  0/598 (0.00%)  1/611 (0.16%) 
Syncope * 1  4/598 (0.67%)  8/611 (1.31%) 
Hypoaesthesia * 1  0/598 (0.00%)  1/611 (0.16%) 
Peripheral motor neuropathy * 1  1/598 (0.17%)  2/611 (0.33%) 
Spinal cord compression * 1  8/598 (1.34%)  2/611 (0.33%) 
Loss of consciousness * 1  0/598 (0.00%)  1/611 (0.16%) 
Presyncope * 1  0/598 (0.00%)  3/611 (0.49%) 
Cerebral ischaemia * 1  2/598 (0.33%)  0/611 (0.00%) 
Convulsion * 1  1/598 (0.17%)  1/611 (0.16%) 
Ataxia * 1  1/598 (0.17%)  0/611 (0.00%) 
Hypotonia * 1  0/598 (0.00%)  1/611 (0.16%) 
Ischaemic stroke * 1  2/598 (0.33%)  0/611 (0.00%) 
Transient ischaemic attack * 1  1/598 (0.17%)  1/611 (0.16%) 
Cerebral infarction * 1  0/598 (0.00%)  1/611 (0.16%) 
Grand mal convulsion * 1  0/598 (0.00%)  1/611 (0.16%) 
Haemorrhagic stroke * 1  1/598 (0.17%)  0/611 (0.00%) 
Leukoencephalopathy * 1  0/598 (0.00%)  1/611 (0.16%) 
Posterior reversible encephalopathy syndrome * 1  0/598 (0.00%)  1/611 (0.16%) 
Vocal cord paralysis * 1  0/598 (0.00%)  1/611 (0.16%) 
Psychiatric disorders     
Anxiety * 1  0/598 (0.00%)  1/611 (0.16%) 
Depression * 1  1/598 (0.17%)  0/611 (0.00%) 
Confusional state * 1  0/598 (0.00%)  1/611 (0.16%) 
Mental status changes * 1  1/598 (0.17%)  0/611 (0.00%) 
Renal and urinary disorders     
Haematuria * 1  4/598 (0.67%)  5/611 (0.82%) 
Proteinuria * 1  0/598 (0.00%)  1/611 (0.16%) 
Urinary retention * 1  3/598 (0.50%)  2/611 (0.33%) 
Hydronephrosis * 1  1/598 (0.17%)  1/611 (0.16%) 
Urethral stenosis * 1  1/598 (0.17%)  1/611 (0.16%) 
Renal colic * 1  1/598 (0.17%)  0/611 (0.00%) 
Nephrotic syndrome * 1  0/598 (0.00%)  1/611 (0.16%) 
Renal failure * 1  1/598 (0.17%)  1/611 (0.16%) 
Urinary tract obstruction * 1  1/598 (0.17%)  0/611 (0.00%) 
Bladder neck obstruction * 1  1/598 (0.17%)  0/611 (0.00%) 
Renal failure acute * 1  0/598 (0.00%)  1/611 (0.16%) 
Ureteric haemorrhage * 1  0/598 (0.00%)  1/611 (0.16%) 
Urethral meatus stenosis * 1  1/598 (0.17%)  0/611 (0.00%) 
Reproductive system and breast disorders     
Genital ulceration * 1  0/598 (0.00%)  1/611 (0.16%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  1/598 (0.17%)  20/611 (3.27%) 
Dyspnoea * 1  3/598 (0.50%)  2/611 (0.33%) 
Oropharyngeal pain * 1  0/598 (0.00%)  2/611 (0.33%) 
Pulmonary embolism * 1  17/598 (2.84%)  13/611 (2.13%) 
Dyspnoea exertional * 1  0/598 (0.00%)  1/611 (0.16%) 
Haemoptysis * 1  1/598 (0.17%)  1/611 (0.16%) 
Hypoxia * 1  0/598 (0.00%)  2/611 (0.33%) 
Pleural effusion * 1  0/598 (0.00%)  1/611 (0.16%) 
Bronchospasm * 1  0/598 (0.00%)  1/611 (0.16%) 
Pneumonitis * 1  0/598 (0.00%)  1/611 (0.16%) 
Respiratory failure * 1  0/598 (0.00%)  2/611 (0.33%) 
Acute respiratory failure * 1  0/598 (0.00%)  2/611 (0.33%) 
Interstitial lung disease * 1  1/598 (0.17%)  1/611 (0.16%) 
Acute respiratory distress syndrome * 1  0/598 (0.00%)  1/611 (0.16%) 
Pneumothorax * 1  0/598 (0.00%)  1/611 (0.16%) 
Vascular disorders     
Hypertension * 1  1/598 (0.17%)  5/611 (0.82%) 
Hypotension * 1  3/598 (0.50%)  4/611 (0.65%) 
Deep vein thrombosis * 1  6/598 (1.00%)  4/611 (0.65%) 
Phlebitis superficial * 1  1/598 (0.17%)  0/611 (0.00%) 
Orthostatic hypotension * 1  1/598 (0.17%)  2/611 (0.33%) 
Hypertensive crisis * 1  0/598 (0.00%)  1/611 (0.16%) 
Subclavian artery stenosis * 1  1/598 (0.17%)  0/611 (0.00%) 
Venous thrombosis limb * 1  0/598 (0.00%)  1/611 (0.16%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Aflibercept
Affected / at Risk (%) Affected / at Risk (%)
Total   551/598 (92.14%)   573/611 (93.78%) 
Eye disorders     
Lacrimation increased * 1  71/598 (11.87%)  119/611 (19.48%) 
Gastrointestinal disorders     
Diarrhoea * 1  209/598 (34.95%)  268/611 (43.86%) 
Stomatitis * 1  123/598 (20.57%)  340/611 (55.65%) 
Nausea * 1  166/598 (27.76%)  165/611 (27.00%) 
Constipation * 1  131/598 (21.91%)  133/611 (21.77%) 
Vomiting * 1  84/598 (14.05%)  90/611 (14.73%) 
Abdominal pain * 1  45/598 (7.53%)  47/611 (7.69%) 
Dyspepsia * 1  29/598 (4.85%)  31/611 (5.07%) 
Haemorrhoids * 1  14/598 (2.34%)  31/611 (5.07%) 
Dysphagia * 1  1/598 (0.17%)  31/611 (5.07%) 
General disorders     
Fatigue * 1  241/598 (40.30%)  243/611 (39.77%) 
Asthenia * 1  123/598 (20.57%)  144/611 (23.57%) 
Oedema peripheral * 1  157/598 (26.25%)  57/611 (9.33%) 
Pyrexia * 1  54/598 (9.03%)  61/611 (9.98%) 
Infections and infestations     
Urinary tract infection * 1  38/598 (6.35%)  39/611 (6.38%) 
Nasopharyngitis * 1  36/598 (6.02%)  23/611 (3.76%) 
Investigations     
Weight decreased * 1  51/598 (8.53%)  201/611 (32.90%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  110/598 (18.39%)  190/611 (31.10%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  83/598 (13.88%)  55/611 (9.00%) 
Arthralgia * 1  66/598 (11.04%)  42/611 (6.87%) 
Pain in extremity * 1  62/598 (10.37%)  42/611 (6.87%) 
Myalgia * 1  58/598 (9.70%)  41/611 (6.71%) 
Bone pain * 1  44/598 (7.36%)  35/611 (5.73%) 
Musculoskeletal pain * 1  33/598 (5.52%)  21/611 (3.44%) 
Muscle spasms * 1  31/598 (5.18%)  17/611 (2.78%) 
Nervous system disorders     
Dysgeusia * 1  107/598 (17.89%)  108/611 (17.68%) 
Headache * 1  45/598 (7.53%)  95/611 (15.55%) 
Neuropathy peripheral * 1  76/598 (12.71%)  56/611 (9.17%) 
Peripheral sensory neuropathy * 1  75/598 (12.54%)  51/611 (8.35%) 
Paraesthesia * 1  49/598 (8.19%)  38/611 (6.22%) 
Dizziness * 1  50/598 (8.36%)  29/611 (4.75%) 
Psychiatric disorders     
Insomnia * 1  44/598 (7.36%)  45/611 (7.36%) 
Renal and urinary disorders     
Proteinuria * 1  6/598 (1.00%)  31/611 (5.07%) 
Respiratory, thoracic and mediastinal disorders     
Dysphonia * 1  36/598 (6.02%)  230/611 (37.64%) 
Epistaxis * 1  55/598 (9.20%)  199/611 (32.57%) 
Cough * 1  77/598 (12.88%)  111/611 (18.17%) 
Dyspnoea * 1  62/598 (10.37%)  89/611 (14.57%) 
Oropharyngeal pain * 1  23/598 (3.85%)  69/611 (11.29%) 
Rhinorrhoea * 1  17/598 (2.84%)  38/611 (6.22%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  268/598 (44.82%)  224/611 (36.66%) 
Nail disorder * 1  97/598 (16.22%)  94/611 (15.38%) 
Rash * 1  33/598 (5.52%)  49/611 (8.02%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  5/598 (0.84%)  51/611 (8.35%) 
Vascular disorders     
Hypertension * 1  66/598 (11.04%)  207/611 (33.88%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
Pain response initially defined as a key secondary endpoint together with PSA response, time to occurence of SRE and PFS was finally considered as an exploratory endpoint in final statistical analysis plan.
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 to a journal, 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: NCT00519285     History of Changes
Other Study ID Numbers: EFC6546
2006-004756-20 ( EudraCT Number )
First Submitted: August 21, 2007
First Posted: August 22, 2007
Results First Submitted: April 25, 2013
Results First Posted: October 10, 2013
Last Update Posted: July 22, 2016