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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00943826
First Posted: July 22, 2009
Last Update Posted: September 25, 2017
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.
Information provided by (Responsible Party):
Hoffmann-La Roche
Results First Submitted: March 29, 2013  
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

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Bevacizumab + RT + Temozolomide 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.
Placebo + RT + Temozolomide 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.

Participant Flow for 4 periods

Period 1:   Concurrent Phase
    Bevacizumab + RT + Temozolomide   Placebo + RT + Temozolomide
STARTED   458   463 
Treated   452   459 
COMPLETED   397   421 
NOT COMPLETED   61   42 
Adverse Event                50                27 
Withdrew consent                3                7 
Refused treatment/Did not cooperate                5                7 
Administrative reasons                2                1 
Protocol Violation                1                0 

Period 2:   Maintenance Phase
    Bevacizumab + RT + Temozolomide   Placebo + RT + Temozolomide
STARTED   396 [1]   370 [1] 
COMPLETED   353   331 
NOT COMPLETED   43   39 
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 3:   Monotherapy Phase
    Bevacizumab + RT + Temozolomide   Placebo + RT + Temozolomide
STARTED   269 [1]   159 [1] 
COMPLETED   204   143 
NOT COMPLETED   65   16 
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 4:   After Primary Overall Survival Analysis
    Bevacizumab + RT + Temozolomide   Placebo + RT + Temozolomide
STARTED   27 [1]   20 [1] 
COMPLETED   0   0 
NOT COMPLETED   27   20 
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.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat population included all randomized participants.

Reporting Groups
  Description
Bevacizumab + RT + Temozolomide 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.
Placebo + RT +Temozolomide 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 Total of all reporting groups

Baseline Measures
   Bevacizumab + RT + Temozolomide   Placebo + RT +Temozolomide   Total 
Overall Participants Analyzed 
[Units: Participants]
 458   463   921 
Age 
[Units: Years]
Mean (Full Range)
 55.9 
 (20 to 84) 
 55.9 
 (18 to 79) 
 55.9 
 (18 to 84) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      176  38.4%      165  35.6%      341  37.0% 
Male      282  61.6%      298  64.4%      580  63.0% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator   [ Time Frame: Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months) ]

2.  Primary:   Co-Primary: Overall Survival (OS)   [ Time Frame: Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months]) ]

3.  Secondary:   PFS as Assessed by an Independent Review Facility   [ Time Frame: Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months]) ]

4.  Secondary:   Kaplan-Meier (KM) Estimate of One Year Overall Survival   [ Time Frame: Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months]) ]

5.  Secondary:   Kaplan-Meier (KM) Estimate of Two Year Overall Survival   [ Time Frame: Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months]) ]

6.  Secondary:   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)   [ Time Frame: Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months) ]

7.  Secondary:   Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death   [ Time Frame: Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months]) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com


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