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A Study of Bevacizumab (Avastin®) in Combination With Temozolomide and Radiotherapy in Participants With Newly Diagnosed Glioblastoma

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ClinicalTrials.gov Identifier: NCT00943826
Recruitment Status : Completed
First Posted : July 22, 2009
Results First Posted : May 20, 2013
Last Update Posted : September 25, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Glioblastoma
Interventions Drug: Bevacizumab
Drug: Temozolomide
Radiation: Radiation therapy
Drug: Placebo
Enrollment 921
Recruitment Details  
Pre-assignment Details The primary completion date for co-primary outcome of Progression-Free Survival (PFS) was 31 Mar 2012, whereas, the primary completion date for co-primary outcome of Overall Survival (OS) was 28 Feb 2013. Data for PFS and OS are reported according to these cut-off dates.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety. In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Period Title: Concurrent Phase
Started 458 463
Treated 452 459
Completed 397 421
Not Completed 61 42
Reason Not Completed
Adverse Event             50             27
Withdrew consent             3             7
Refused treatment/Did not cooperate             5             7
Administrative reasons             2             1
Protocol Violation             1             0
Period Title: Maintenance Phase
Started 396 [1] 370 [1]
Completed 353 331
Not Completed 43 39
Reason Not Completed
Adverse Event             31             30
Withdrew consent             2             4
Refused treatment/Did not cooperate             6             3
Administrative reasons             4             1
Failure to return             0             1
[1]
Some who completed previous period had discontinued, progressed, or died prior to this period.
Period Title: Monotherapy Phase
Started 269 [1] 159 [1]
Completed 204 143
Not Completed 65 16
Reason Not Completed
Adverse Event             42             5
Administrative reasons             11             5
Refused treatment/ Did not cooperate             8             2
Withdrew Consent             2             3
Failure to return             2             1
[1]
Some who completed previous period had discontinued, progressed, or died prior to this period.
Period Title: After Primary Overall Survival Analysis
Started 27 [1] 20 [1]
Completed 0 0
Not Completed 27 20
Reason Not Completed
Adverse Event             11             0
Administrative reasons             10             16
Progression of Disease             2             4
Withdrew Consent             4             0
[1]
Some who completed previous period had discontinued, progressed, or died prior to this period.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT +Temozolomide Total
Hide Arm/Group Description In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety. In the Concurrent Phase participants received RT in daily fractions of 2 Gy given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety. Total of all reporting groups
Overall Number of Baseline Participants 458 463 921
Hide Baseline Analysis Population Description
Intent to treat population included all randomized participants.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 458 participants 463 participants 921 participants
55.9
(20 to 84)
55.9
(18 to 79)
55.9
(18 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 458 participants 463 participants 921 participants
Female
176
  38.4%
165
  35.6%
341
  37.0%
Male
282
  61.6%
298
  64.4%
580
  63.0%
1.Primary Outcome
Title Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator
Hide Description PFS is defined as time from randomization to disease progression (PD) or death. PD was assessed using adapted Macdonald response criteria (modified World Health Organization [WHO] criteria) based on 3 components: radiological tumor assessments using Magnetic Resonance Imaging [MRI] scans,neurological assessment and changes in corticosteroid use. PD is assessed as greater than or equal to(>=) 25% increase in sum of products of the longest diameters of all index lesions (enhancing,measurable) compared with the smallest recorded sum (nadir); or unequivocal PD of existing non-index lesions (non-enhancing and enhancing,non-measurable); or unequivocal appearance of new lesions); or neurological worsening (if corticosteroid dose is stable or increased) compared to neurological evaluation at previous disease assessment with no need for a confirmatory scan. Participants without a PFS event were censored at last disease assessment.
Time Frame Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description:
In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Overall Number of Participants Analyzed 458 463
Median (95% Confidence Interval)
Unit of Measure: Months
10.6
(10.0 to 11.4)
6.2
(6.0 to 7.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + RT + Temozolomide, Placebo + RT + Temozolomide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Stratified by Region and Recursive partitioning analysis (RPA) Class
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.55 to 0.74
Estimation Comments Stratified by Region and RPA Class.
2.Primary Outcome
Title Co-Primary: Overall Survival (OS)
Hide Description Overall Survival was defined as the time from randomization to death due to any cause.
Time Frame Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description:
In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Overall Number of Participants Analyzed 458 463
Median (95% Confidence Interval)
Unit of Measure: Months
16.8
(15.5 to 18.5)
16.7
(15.4 to 18.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + RT + Temozolomide, Placebo + RT + Temozolomide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0987
Comments [Not Specified]
Method Log Rank
Comments Stratified by Region and RPA Class
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.76 to 1.02
Estimation Comments Stratified by Region and RPA Class.
3.Secondary Outcome
Title PFS as Assessed by an Independent Review Facility
Hide Description An Independent Review Facility reviewed the MRI scans used by investigator to evaluate radiological tumor response. PFS is defined as time from randomization to PD or death. PD was assessed using adapted Macdonald response (modified WHO) criteria based on 3 components: radiological tumor assessments using MRI scans, neurological assessment and changes in corticosteroid use. PD is assessed as >=25% increase in sum of products of the longest diameters of all index lesions (enhancing, measurable) compared with the smallest recorded sum (nadir); or unequivocal PD of existing non-index lesions (non-enhancing and enhancing, non-measurable); or unequivocal appearance of new lesions); or neurological worsening (if corticosteroid dose is stable or increased) compared to neurological evaluation at previous disease assessment with no need for a confirmatory scan. Participants without a PFS event were censored at last disease assessment.
Time Frame Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population.
Arm/Group Title Bevacizumab + RT +Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description:
In the Concurrent Phase participants received RT in daily fractions of 2 Gy given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab 10 mg/kg IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity.
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Overall Number of Participants Analyzed 458 463
Median (95% Confidence Interval)
Unit of Measure: Months
8.4
(7.9 to 9.7)
4.3
(4.1 to 5.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab + RT +Temozolomide, Placebo + RT + Temozolomide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Stratified by Region and RPA Class.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.53 to 0.71
Estimation Comments Stratified by Region and RPA Class.
4.Secondary Outcome
Title Kaplan-Meier (KM) Estimate of One Year Overall Survival
Hide Description KM estimate of one year overall survival (probability to survive for at least 1 year) was reported. Corresponding 95% confidence interval (CI) was calculated using Greenwood's formula.
Time Frame Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description:
In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Overall Number of Participants Analyzed 458 463
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability of being alive
0.72
(0.68 to 0.77)
0.66
(0.62 to 0.71)
5.Secondary Outcome
Title Kaplan-Meier (KM) Estimate of Two Year Overall Survival
Hide Description KM estimate of two year overall survival was reported (probability to survive for at least 2 years). Corresponding 95% CI was calculated using Greenwood’s formula.
Time Frame Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description:
In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Overall Number of Participants Analyzed 458 463
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability of being alive
0.34
(0.29 to 0.38)
0.30
(0.26 to 0.34)
6.Secondary Outcome
Title PFS in Participants With Stable/Improved Health Related Quality of Life (HRQoL) Based on European Organization for Research & Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30)(EORTC QLQ-C30) & EORTC QLQ Brain Neoplasm 20 (BN20)
Hide Description EORTC QLQ-C30: 30 items; 5 functional scales; 9 symptom scales; & global health status. Most questions used 4-point scale (1:Not at all, 4:Very much), 2 questions used 7-point scale (1:very poor, 7:Excellent). EORTC QLQ-BN20: 20 items rated on a 4 point scale (1:not at all, 4:very much). EORTC QLQ-C30 and BN20 scores were transformed to a 0-100 scale, higher score=better functioning/global health (C30) or more severe symptoms (BN20). Stable HRQoL: change from baseline (BL) within 10 points. Improved HRQoL: an increase from BL >/=10 points for functioning/global health status, & decrease of >/=10 points for symptoms. PFS is reported for participants with Stable/Improved global health; physical, social functioning (C30); motor dysfunction & communication deficit (BN20). PFS: randomization to PD or death. PD: >=25% increase in sum of products of longest diameters of index lesions; or progression of existing non-index lesions; or appearance of new lesions; or neurological worsening.
Time Frame Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population. Number of Participants Analyzed = overall participants evaluable for this outcome measure; n = participants evaluable for specified category.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description:
In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Overall Number of Participants Analyzed 458 463
Median (Full Range)
Unit of Measure: Months
Global health status (n=354, 309)
8
(0 to 26)
4
(1 to 29)
Physical functioning (n=353, 318)
7
(0 to 27)
5
(1 to 29)
Social functioning (n=352, 327)
8
(0 to 26)
4
(0 to 27)
Motor dysfunction (n=361, 314)
7
(1 to 27)
4
(0 to 26)
Communication deficit (n=365, 329)
8
(0 to 27)
4
(1 to 24)
7.Secondary Outcome
Title Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death
Hide Description An adverse event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as AE.A serious adverse event (SAE) is any experience that suggests a significant hazard,contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Non-serious adverse events (Non-SAEs) included all AEs except SAEs (non-SAEs = all AEs – SAEs). Nine participants randomized to the Placebo+RT+Temozolomide arm incorrectly received at least 1 dose of bevacizumab and were added to the Bevacizumab+RT+Temozolomide arm for Safety.
Time Frame Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all randomized participants who received study treatment during the treatment period (10 participants did not receive at least one dose of study treatment and were therefore excluded, 4 in Placebo and 6 in Bevacizumab.
Arm/Group Title Bevacizumab + RT + Temozolomide Placebo + RT + Temozolomide
Hide Arm/Group Description:
In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gray (Gy) given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 milligrams per square meter (mg/m^2) daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab (Avastin) 10 milligrams per kilogram (mg/kg) intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
Overall Number of Participants Analyzed 461 450
Measure Type: Number
Unit of Measure: Participants
Non-SAEs 437 412
SAEs 179 115
Death 335 337
Time Frame Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
Adverse Event Reporting Description Safety Population.10 participants did not receive at least 1 dose of drug and were excluded, 4 in Placebo and 6 in Bevacizumab.9 participants randomized to the Placebo+RT+Temozolomide arm incorrectly received at least 1 dose of bevacizumab and were added to the Bevacizumab+RT+Temozolomide arm for safety.Other AEs are non-SAEs (AEs excluding SAEs).
 
Arm/Group Title Bevacizumab + RT+Temozolomide Placebo + RT+Temozolomide
Hide Arm/Group Description In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and bevacizumab 10 mg/kg intravenous (IV) every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of bevacizumab 10 mg/kg IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received bevacizumab 15 mg/kg IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety. In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per weeks for 6 weeks (for a total of 60 Gy) and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (for a maximum of 49 days in case of delay to the end of radiation therapy) and placebo IV every 2 weeks for 6 weeks. There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of placebo IV every 2 weeks and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants then entered the Monotherapy Phase where they received placebo IV every 3 weeks until disease progression/unacceptable toxicity. Participants then entered the last period: After Primary Overall Survival Analysis, in which participants were followed up for safety.
All-Cause Mortality
Bevacizumab + RT+Temozolomide Placebo + RT+Temozolomide
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab + RT+Temozolomide Placebo + RT+Temozolomide
Affected / at Risk (%) Affected / at Risk (%)
Total   179/461 (38.83%)   115/450 (25.56%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  17/461 (3.69%)  8/450 (1.78%) 
Neutropenia  1  4/461 (0.87%)  2/450 (0.44%) 
Pancytopenia  1  5/461 (1.08%)  1/450 (0.22%) 
Anaemia  1  3/461 (0.65%)  0/450 (0.00%) 
Febrile bone marrow aplasia  1  1/461 (0.22%)  1/450 (0.22%) 
Febrile neutropenia  1  1/461 (0.22%)  1/450 (0.22%) 
Leukopenia  1  0/461 (0.00%)  2/450 (0.44%) 
Eosinophilia  1  1/461 (0.22%)  0/450 (0.00%) 
Thrombotic microangiopathy  1  1/461 (0.22%)  0/450 (0.00%) 
Cardiac disorders     
Myocardial infarction  1  3/461 (0.65%)  0/450 (0.00%) 
Angina pectoris  1  1/461 (0.22%)  0/450 (0.00%) 
Atrial fibrillation  1  1/461 (0.22%)  0/450 (0.00%) 
Cardiac arrest  1  1/461 (0.22%)  0/450 (0.00%) 
Cardiac failure congestive  1  1/461 (0.22%)  0/450 (0.00%) 
Cardio-respiratory arrest  1  0/461 (0.00%)  1/450 (0.22%) 
Cardiovascular disorder  1  1/461 (0.22%)  0/450 (0.00%) 
Coronary artery stenosis  1  2/461 (0.43%)  0/450 (0.00%) 
Myocardial ischaemia  1  1/461 (0.22%)  0/450 (0.00%) 
Tachyarrhythmia  1  0/461 (0.00%)  1/450 (0.22%) 
Acute Myocardial Infarction  1  1/461 (0.22%)  0/450 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  1/461 (0.22%)  0/450 (0.00%) 
Vertigo positional  1  1/461 (0.22%)  0/450 (0.00%) 
Endocrine disorders     
Diabetes insipidus  1  0/461 (0.00%)  1/450 (0.22%) 
Eye disorders     
Optic Neuropathy  1  1/461 (0.22%)  0/450 (0.00%) 
Gastrointestinal disorders     
Vomiting  1  5/461 (1.08%)  5/450 (1.11%) 
Abdominal pain  1  4/461 (0.87%)  0/450 (0.00%) 
Diarrhoea  1  2/461 (0.43%)  1/450 (0.22%) 
Large intestine perforation  1  1/461 (0.22%)  1/450 (0.22%) 
Anal prolapse  1  1/461 (0.22%)  0/450 (0.00%) 
Colitis  1  1/461 (0.22%)  0/450 (0.00%) 
Dyspepsia  1  1/461 (0.22%)  0/450 (0.00%) 
Faecaloma  1  1/461 (0.22%)  0/450 (0.00%) 
Gastrointestinal haemorrhage  1  0/461 (0.00%)  1/450 (0.22%) 
Gastrooesophageal reflux disease  1  1/461 (0.22%)  0/450 (0.00%) 
Haematemesis  1  1/461 (0.22%)  0/450 (0.00%) 
Intestinal perforation  1  1/461 (0.22%)  0/450 (0.00%) 
Nausea  1  0/461 (0.00%)  1/450 (0.22%) 
Oesophageal ulcer  1  1/461 (0.22%)  0/450 (0.00%) 
Pancreatitis  1  0/461 (0.00%)  1/450 (0.22%) 
Rectal perforation  1  1/461 (0.22%)  0/450 (0.00%) 
Stomatitis  1  1/461 (0.22%)  0/450 (0.00%) 
Subileus  1  0/461 (0.00%)  1/450 (0.22%) 
Inguinal Hernia  1  1/461 (0.22%)  0/450 (0.00%) 
General disorders     
Pyrexia  1  8/461 (1.74%)  3/450 (0.67%) 
General physical health deterioration  1  3/461 (0.65%)  2/450 (0.44%) 
Fatigue  1  0/461 (0.00%)  2/450 (0.44%) 
Cyst  1  1/461 (0.22%)  0/450 (0.00%) 
Death  1  0/461 (0.00%)  1/450 (0.22%) 
Impaired healing  1  1/461 (0.22%)  0/450 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  2/461 (0.43%)  0/450 (0.00%) 
Cholangitis  1  1/461 (0.22%)  0/450 (0.00%) 
Cholelithiasis  1  1/461 (0.22%)  0/450 (0.00%) 
Hepatic function abnormal  1  0/461 (0.00%)  1/450 (0.22%) 
Hyperbilirubinaemia  1  0/461 (0.00%)  1/450 (0.22%) 
Cholecystitis Acute  1  1/461 (0.22%)  0/450 (0.00%) 
Drug−induced liver injury  1  1/461 (0.22%)  0/450 (0.00%) 
Infections and infestations     
Pneumonia  1  10/461 (2.17%)  5/450 (1.11%) 
Sepsis  1  6/461 (1.30%)  1/450 (0.22%) 
Urinary tract infection  1  1/461 (0.22%)  3/450 (0.67%) 
Brain abscess  1  1/461 (0.22%)  3/450 (0.67%) 
Lower respiratory tract infection  1  0/461 (0.00%)  3/450 (0.67%) 
Pneumocystis jiroveci pneumonia  1  1/461 (0.22%)  2/450 (0.44%) 
Postoperative wound infection  1  3/461 (0.65%)  0/450 (0.00%) 
Respiratory tract infection  1  1/461 (0.22%)  2/450 (0.44%) 
Septic shock  1  2/461 (0.43%)  1/450 (0.22%) 
Infection  1  2/461 (0.43%)  0/450 (0.00%) 
Meningitis  1  1/461 (0.22%)  1/450 (0.22%) 
Upper respiratory tract infection  1  1/461 (0.22%)  1/450 (0.22%) 
Wound infection  1  3/461 (0.65%)  0/450 (0.00%) 
Abscess  1  1/461 (0.22%)  0/450 (0.00%) 
Acute tonsillitis  1  0/461 (0.00%)  1/450 (0.22%) 
Anal abscess  1  1/461 (0.22%)  0/450 (0.00%) 
Bacteraemia  1  1/461 (0.22%)  0/450 (0.00%) 
Bronchopneumonia  1  0/461 (0.00%)  1/450 (0.22%) 
Cellulitis  1  1/461 (0.22%)  0/450 (0.00%) 
Cytomegalovirus infection  1  1/461 (0.22%)  0/450 (0.00%) 
Diverticulitis  1  0/461 (0.00%)  1/450 (0.22%) 
Encephalitis herpes  1  1/461 (0.22%)  0/450 (0.00%) 
Erysipelas  1  1/461 (0.22%)  0/450 (0.00%) 
Gastroenteritis  1  1/461 (0.22%)  0/450 (0.00%) 
Gastroenteritis viral  1  1/461 (0.22%)  0/450 (0.00%) 
Graft infection  1  1/461 (0.22%)  0/450 (0.00%) 
Helicobacter infection  1  1/461 (0.22%)  0/450 (0.00%) 
Hepatitis B  1  1/461 (0.22%)  0/450 (0.00%) 
Herpes simplex  1  0/461 (0.00%)  1/450 (0.22%) 
Herpes zoster  1  1/461 (0.22%)  0/450 (0.00%) 
Infectious pleural effusion  1  1/461 (0.22%)  0/450 (0.00%) 
Lobar pneumonia  1  1/461 (0.22%)  0/450 (0.00%) 
Lung infection  1  0/461 (0.00%)  1/450 (0.22%) 
Neutropenic sepsis  1  1/461 (0.22%)  0/450 (0.00%) 
Oesophageal candidiasis  1  1/461 (0.22%)  0/450 (0.00%) 
Oral fungal infection  1  1/461 (0.22%)  0/450 (0.00%) 
Parotitis  1  1/461 (0.22%)  0/450 (0.00%) 
Pneumonia respiratory syncytial viral  1  0/461 (0.00%)  1/450 (0.22%) 
Post procedural infection  1  0/461 (0.00%)  2/450 (0.44%) 
Sinusitis  1  1/461 (0.22%)  0/450 (0.00%) 
Streptococcal sepsis  1  1/461 (0.22%)  0/450 (0.00%) 
Urosepsis  1  2/461 (0.43%)  0/450 (0.00%) 
Viral infection  1  1/461 (0.22%)  0/450 (0.00%) 
Wound infection staphylococcal  1  1/461 (0.22%)  0/450 (0.00%) 
Pyelonephritis  1  1/461 (0.22%)  0/450 (0.00%) 
Staphylococcal Infection  1  1/461 (0.22%)  0/450 (0.00%) 
Extradural Abscess  1  1/461 (0.22%)  0/450 (0.00%) 
Injury, poisoning and procedural complications     
Spinal compression fracture  1  1/461 (0.22%)  2/450 (0.44%) 
Lumbar vertebral fracture  1  1/461 (0.22%)  1/450 (0.22%) 
Spinal fracture  1  0/461 (0.00%)  2/450 (0.44%) 
Fall  1  1/461 (0.22%)  0/450 (0.00%) 
Ankle fracture  1  1/461 (0.22%)  0/450 (0.00%) 
Head injury  1  1/461 (0.22%)  0/450 (0.00%) 
Incision site haemorrhage  1  0/461 (0.00%)  1/450 (0.22%) 
Post procedural complication  1  0/461 (0.00%)  1/450 (0.22%) 
Radiation necrosis  1  0/461 (0.00%)  1/450 (0.22%) 
Toxicity to various agents  1  0/461 (0.00%)  1/450 (0.22%) 
Wound complication  1  0/461 (0.00%)  1/450 (0.22%) 
Wound dehiscence  1  0/461 (0.00%)  1/450 (0.22%) 
Wound secretion  1  1/461 (0.22%)  0/450 (0.00%) 
Wrist fracture  1  1/461 (0.22%)  0/450 (0.00%) 
Subdural Haematoma  1  1/461 (0.22%)  0/450 (0.00%) 
Investigations     
Troponin increased  1  0/461 (0.00%)  1/450 (0.22%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/461 (0.22%)  5/450 (1.11%) 
Dehydration  1  2/461 (0.43%)  3/450 (0.67%) 
Decreased appetite  1  0/461 (0.00%)  3/450 (0.67%) 
Diabetes mellitus  1  1/461 (0.22%)  0/450 (0.00%) 
Hypoalbuminaemia  1  0/461 (0.00%)  1/450 (0.22%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal chest pain  1  3/461 (0.65%)  0/450 (0.00%) 
Back pain  1  1/461 (0.22%)  1/450 (0.22%) 
Muscular weakness  1  2/461 (0.43%)  0/450 (0.00%) 
Myopathy  1  0/461 (0.00%)  1/450 (0.22%) 
Synovial cyst  1  0/461 (0.00%)  1/450 (0.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour haemorrhage  1  3/461 (0.65%)  1/450 (0.22%) 
Bladder cancer  1  1/461 (0.22%)  0/450 (0.00%) 
Intracranial tumour haemorrhage  1  1/461 (0.22%)  0/450 (0.00%) 
Prostate cancer  1  1/461 (0.22%)  0/450 (0.00%) 
Thyroid adenoma  1  1/461 (0.22%)  0/450 (0.00%) 
Basal Cell Carcinoma  1  1/461 (0.22%)  0/450 (0.00%) 
Metastasis to liver  1  0/461 (0.00%)  1/450 (0.22%) 
Nervous system disorders     
Convulsion  1  5/461 (1.08%)  6/450 (1.33%) 
Cerebrovascular accident  1  8/461 (1.74%)  2/450 (0.44%) 
Brain oedema  1  2/461 (0.43%)  4/450 (0.89%) 
Headache  1  4/461 (0.87%)  2/450 (0.44%) 
Cerebral ischaemia  1  3/461 (0.65%)  2/450 (0.44%) 
Epilepsy  1  3/461 (0.65%)  2/450 (0.44%) 
Ischaemic stroke  1  2/461 (0.43%)  1/450 (0.22%) 
Somnolence  1  3/461 (0.65%)  0/450 (0.00%) 
Dizziness  1  0/461 (0.00%)  2/450 (0.44%) 
Haemorrhage intracranial  1  0/461 (0.00%)  2/450 (0.44%) 
Hemiparesis  1  1/461 (0.22%)  1/450 (0.22%) 
Hydrocephalus  1  2/461 (0.43%)  0/450 (0.00%) 
Intracranial pressure increased  1  1/461 (0.22%)  1/450 (0.22%) 
Neurological decompensation  1  1/461 (0.22%)  1/450 (0.22%) 
Balance disorder  1  0/461 (0.00%)  1/450 (0.22%) 
Basal ganglia stroke  1  1/461 (0.22%)  0/450 (0.00%) 
Cerebral haemorrhage  1  1/461 (0.22%)  0/450 (0.00%) 
Cerebral thrombosis  1  0/461 (0.00%)  1/450 (0.22%) 
Encephalitis  1  1/461 (0.22%)  0/450 (0.00%) 
Encephalopathy  1  1/461 (0.22%)  0/450 (0.00%) 
Grand mal convulsion  1  0/461 (0.00%)  1/450 (0.22%) 
Haemorrhagic stroke  1  0/461 (0.00%)  1/450 (0.22%) 
Leukoencephalopathy  1  1/461 (0.22%)  0/450 (0.00%) 
Nervous system disorder  1  0/461 (0.00%)  1/450 (0.22%) 
Paraesthesia  1  1/461 (0.22%)  0/450 (0.00%) 
Partial seizures  1  1/461 (0.22%)  0/450 (0.00%) 
Pyramidal tract syndrome  1  0/461 (0.00%)  1/450 (0.22%) 
Speech disorder  1  1/461 (0.22%)  0/450 (0.00%) 
Syncope  1  1/461 (0.22%)  0/450 (0.00%) 
Psychiatric disorders     
Acute psychosis  1  1/461 (0.22%)  0/450 (0.00%) 
Anxiety  1  1/461 (0.22%)  0/450 (0.00%) 
Confusional state  1  0/461 (0.00%)  1/450 (0.22%) 
Delirium  1  1/461 (0.22%)  0/450 (0.00%) 
Delirium tremens  1  1/461 (0.22%)  0/450 (0.00%) 
Mania  1  1/461 (0.22%)  0/450 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/461 (0.22%)  0/450 (0.00%) 
Nephrotic syndrome  1  1/461 (0.22%)  0/450 (0.00%) 
Proteinuria  1  1/461 (0.22%)  0/450 (0.00%) 
Renal failure acute  1  1/461 (0.22%)  0/450 (0.00%) 
Urinary retention  1  1/461 (0.22%)  0/450 (0.00%) 
Reproductive system and breast disorders     
Scrotal cyst  1  1/461 (0.22%)  0/450 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  13/461 (2.82%)  12/450 (2.67%) 
Lung disorder  1  2/461 (0.43%)  1/450 (0.22%) 
Acute respiratory distress syndrome  1  1/461 (0.22%)  0/450 (0.00%) 
Aspiration  1  1/461 (0.22%)  0/450 (0.00%) 
Chronic obstructive pulmonary disease  1  1/461 (0.22%)  0/450 (0.00%) 
Epistaxis  1  1/461 (0.22%)  0/450 (0.00%) 
Pleural effusion  1  0/461 (0.00%)  1/450 (0.22%) 
Sleep apnoea syndrome  1  1/461 (0.22%)  0/450 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/461 (0.22%)  1/450 (0.22%) 
Drug eruption  1  0/461 (0.00%)  1/450 (0.22%) 
Skin ulcer  1  1/461 (0.22%)  0/450 (0.00%) 
Toxic skin eruption  1  1/461 (0.22%)  0/450 (0.00%) 
Prurigo  1  1/461 (0.22%)  0/450 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  11/461 (2.39%)  6/450 (1.33%) 
Hypertension  1  4/461 (0.87%)  1/450 (0.22%) 
Venous thrombosis  1  0/461 (0.00%)  2/450 (0.44%) 
Embolism  1  1/461 (0.22%)  0/450 (0.00%) 
Embolism venous  1  0/461 (0.00%)  1/450 (0.22%) 
Peripheral arterial occlusive disease  1  1/461 (0.22%)  0/450 (0.00%) 
Thrombophlebitis  1  2/461 (0.43%)  0/450 (0.00%) 
Thrombosis  1  1/461 (0.22%)  0/450 (0.00%) 
Hypotension  1  1/461 (0.22%)  0/450 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab + RT+Temozolomide Placebo + RT+Temozolomide
Affected / at Risk (%) Affected / at Risk (%)
Total   437/461 (94.79%)   412/450 (91.56%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  148/461 (32.10%)  120/450 (26.67%) 
Neutropenia  1  66/461 (14.32%)  53/450 (11.78%) 
Leukopenia  1  56/461 (12.15%)  40/450 (8.89%) 
Lymphopenia  1  34/461 (7.38%)  39/450 (8.67%) 
Anaemia  1  27/461 (5.86%)  34/450 (7.56%) 
Gastrointestinal disorders     
Nausea  1  223/461 (48.37%)  191/450 (42.44%) 
Constipation  1  178/461 (38.61%)  137/450 (30.44%) 
Vomiting  1  145/461 (31.45%)  100/450 (22.22%) 
Diarrhoea  1  95/461 (20.61%)  69/450 (15.33%) 
Abdominal pain  1  33/461 (7.16%)  17/450 (3.78%) 
Dyspepsia  1  31/461 (6.72%)  16/450 (3.56%) 
Abdominal pain upper  1  35/461 (7.59%)  12/450 (2.67%) 
Gingival bleeding  1  36/461 (7.81%)  6/450 (1.33%) 
General disorders     
Fatigue  1  191/461 (41.43%)  178/450 (39.56%) 
Asthenia  1  86/461 (18.66%)  63/450 (14.00%) 
Oedema peripheral  1  36/461 (7.81%)  34/450 (7.56%) 
Pyrexia  1  39/461 (8.46%)  26/450 (5.78%) 
Infections and infestations     
Nasopharyngitis  1  63/461 (13.67%)  26/450 (5.78%) 
Urinary tract infection  1  49/461 (10.63%)  27/450 (6.00%) 
Upper respiratory tract infection  1  31/461 (6.72%)  13/450 (2.89%) 
Injury, poisoning and procedural complications     
Radiation skin injury  1  38/461 (8.24%)  42/450 (9.33%) 
Investigations     
Weight decreased  1  36/461 (7.81%)  18/450 (4.00%) 
Alanine aminotransferase increased  1  22/461 (4.77%)  25/450 (5.56%) 
Metabolism and nutrition disorders     
Decreased appetite  1  116/461 (25.16%)  74/450 (16.44%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  71/461 (15.40%)  30/450 (6.67%) 
Pain in extremity  1  48/461 (10.41%)  22/450 (4.89%) 
Back pain  1  37/461 (8.03%)  29/450 (6.44%) 
Muscular weakness  1  29/461 (6.29%)  33/450 (7.33%) 
Musculoskeletal pain  1  39/461 (8.46%)  12/450 (2.67%) 
Myalgia  1  28/461 (6.07%)  12/450 (2.67%) 
Nervous system disorders     
Headache  1  172/461 (37.31%)  130/450 (28.89%) 
Dizziness  1  46/461 (9.98%)  53/450 (11.78%) 
Dysgeusia  1  39/461 (8.46%)  33/450 (7.33%) 
Convulsion  1  36/461 (7.81%)  39/450 (8.67%) 
Psychiatric disorders     
Insomnia  1  53/461 (11.50%)  42/450 (9.33%) 
Depression  1  43/461 (9.33%)  30/450 (6.67%) 
Anxiety  1  29/461 (6.29%)  25/450 (5.56%) 
Renal and urinary disorders     
Proteinuria  1  72/461 (15.62%)  19/450 (4.22%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  98/461 (21.26%)  22/450 (4.89%) 
Cough  1  55/461 (11.93%)  46/450 (10.22%) 
Dysphonia  1  42/461 (9.11%)  7/450 (1.56%) 
Dyspnoea  1  26/461 (5.64%)  18/450 (4.00%) 
Oropharyngeal pain  1  29/461 (6.29%)  12/450 (2.67%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  180/461 (39.05%)  162/450 (36.00%) 
Rash  1  76/461 (16.49%)  60/450 (13.33%) 
Pruritus  1  54/461 (11.71%)  37/450 (8.22%) 
Dry skin  1  34/461 (7.38%)  24/450 (5.33%) 
Vascular disorders     
Hypertension  1  175/461 (37.96%)  51/450 (11.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00943826     History of Changes
Other Study ID Numbers: BO21990
2008-006146-26 ( EudraCT Number )
First Submitted: July 17, 2009
First Posted: July 22, 2009
Results First Submitted: March 29, 2013
Results First Posted: May 20, 2013
Last Update Posted: September 25, 2017