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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00943826




Registration number
NCT00943826
Ethics application status
Date submitted
17/07/2009
Date registered
21/07/2009
Date last updated
25/08/2017

Titles & IDs
Public title
A Study of Bevacizumab (Avastin®) in Combination With Temozolomide and Radiotherapy in Participants With Newly Diagnosed Glioblastoma
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of Bevacizumab, Temozolomide and Radiotherapy, Followed by Bevacizumab and Temozolomide Versus Placebo, Temozolomide and Radiotherapy Followed by Placebo and Temozolomide in Patients With Newly Diagnosed Glioblastoma
Secondary ID [1] 0 0
2008-006146-26
Secondary ID [2] 0 0
BO21990
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Glioblastoma 0 0
Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Temozolomide
Treatment: Other - Radiation therapy
Treatment: Drugs - Placebo
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Temozolomide
Treatment: Other - Radiation therapy
Treatment: Drugs - Placebo
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Temozolomide
Treatment: Other - Radiation therapy
Treatment: Drugs - Placebo

Experimental: Bevacizumab + RT + Temozolomide - In the Concurrent Phase participants will receive radiotherapy (RT) in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue 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 will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they receive six 28-day cycle of bevacizumab 10 mg/kg IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive bevacizumab 15 mg/kg IV q3w until disease progression/unacceptable toxicity.

Placebo Comparator: Placebo + RT + Temozolomide - In the Concurrent Phase participants will receive radiotherapy in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue 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 will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they will receive six 28-day cycle of placebo IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive placebo IV q3w until disease progression/unacceptable toxicity.

Experimental: Bevacizumab + RT + Temozolomide - In the Concurrent Phase participants will receive radiotherapy (RT) in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue 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 will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they receive six 28-day cycle of bevacizumab 10 mg/kg IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive bevacizumab 15 mg/kg IV q3w until disease progression/unacceptable toxicity.

Placebo Comparator: Placebo + RT + Temozolomide - In the Concurrent Phase participants will receive radiotherapy in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue 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 will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they will receive six 28-day cycle of placebo IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive placebo IV q3w until disease progression/unacceptable toxicity.

Experimental: Bevacizumab + RT + Temozolomide - In the Concurrent Phase participants will receive radiotherapy (RT) in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue 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 will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they receive six 28-day cycle of bevacizumab 10 mg/kg IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive bevacizumab 15 mg/kg IV q3w until disease progression/unacceptable toxicity.

Placebo Comparator: Placebo + RT + Temozolomide - In the Concurrent Phase participants will receive radiotherapy in daily fractions of 2 Gy to be given 5 days per week for 6 weeks and temozolomide 75 mg/m^2 daily from the first day to the last day of radiotherapy (it may continue 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 will be a 4 week treatment break. Participants will then enter the Maintenance Phase where they will receive six 28-day cycle of placebo IV q2w and temozolomide 150 to 200 mg/m^2 daily in the first 5 days of each cycle. The participants will then enter the Monotherapy Phase where they will receive placebo IV q3w until disease progression/unacceptable toxicity.


Treatment: Drugs: Bevacizumab
10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase.

Treatment: Drugs: Temozolomide
75 mg/m^2 once daily for 6 weeks, followed by 150-200 mg/m^2 once daily on days 1-5 of six 4 week cycles.

Treatment: Other: Radiation therapy
30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.

Treatment: Drugs: Placebo
Intravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase.

Treatment: Drugs: Bevacizumab
10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase.

Treatment: Drugs: Temozolomide
75 mg/m^2 once daily for 6 weeks, followed by 150-200 mg/m^2 once daily on days 1-5 of six 4 week cycles.

Treatment: Other: Radiation therapy
30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.

Treatment: Drugs: Placebo
Intravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase.

Treatment: Drugs: Bevacizumab
10 mg/kg intravenously q2w in the Concurrent and Maintenance Phases. 15 mg/kg intravenously q3w in the Monotherapy Phase.

Treatment: Drugs: Temozolomide
75 mg/m^2 once daily for 6 weeks, followed by 150-200 mg/m^2 once daily on days 1-5 of six 4 week cycles.

Treatment: Other: Radiation therapy
30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks.

Treatment: Drugs: Placebo
Intravenously q2w in the Concurrent and Maintenance Phases and q3w in the Monotherapy Phase.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator - 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.
Timepoint [1] 0 0
Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Primary outcome [2] 0 0
Co-Primary: Overall Survival (OS) - Overall Survival was defined as the time from randomization to death due to any cause.
Timepoint [2] 0 0
Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Primary outcome [3] 0 0
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator - 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.
Timepoint [3] 0 0
Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Primary outcome [4] 0 0
Co-Primary: Overall Survival (OS) - Overall Survival was defined as the time from randomization to death due to any cause.
Timepoint [4] 0 0
Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Primary outcome [5] 0 0
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator - 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.
Timepoint [5] 0 0
Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Primary outcome [6] 0 0
Co-Primary: Overall Survival (OS) - Overall Survival was defined as the time from randomization to death due to any cause.
Timepoint [6] 0 0
Randomization until OS Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcome [1] 0 0
PFS as Assessed by an Independent Review Facility - 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.
Timepoint [1] 0 0
Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months])
Secondary outcome [2] 0 0
Kaplan-Meier (KM) Estimate of One Year Overall Survival - 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.
Timepoint [2] 0 0
Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcome [3] 0 0
Kaplan-Meier (KM) Estimate of Two Year Overall Survival - 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.
Timepoint [3] 0 0
Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcome [4] 0 0
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) - 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.
Timepoint [4] 0 0
Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Secondary outcome [5] 0 0
Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death - 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.
Timepoint [5] 0 0
Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
Secondary outcome [6] 0 0
PFS as Assessed by an Independent Review Facility - 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.
Timepoint [6] 0 0
Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months])
Secondary outcome [7] 0 0
Kaplan-Meier (KM) Estimate of One Year Overall Survival - 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.
Timepoint [7] 0 0
Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcome [8] 0 0
Kaplan-Meier (KM) Estimate of Two Year Overall Survival - 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.
Timepoint [8] 0 0
Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcome [9] 0 0
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) - 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.
Timepoint [9] 0 0
Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Secondary outcome [10] 0 0
Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death - 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.
Timepoint [10] 0 0
Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])
Secondary outcome [11] 0 0
PFS as Assessed by an Independent Review Facility - 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.
Timepoint [11] 0 0
Randomization until PFS Event (Until data cutoff= 31 March 2012 [up to 29.5 months])
Secondary outcome [12] 0 0
Kaplan-Meier (KM) Estimate of One Year Overall Survival - 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.
Timepoint [12] 0 0
Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcome [13] 0 0
Kaplan-Meier (KM) Estimate of Two Year Overall Survival - 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.
Timepoint [13] 0 0
Randomization until Overall Survival Event (Until data cutoff= 28 February 2013 [up to 42.2 months])
Secondary outcome [14] 0 0
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) - 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.
Timepoint [14] 0 0
Randomization until PFS Event [Until data cutoff= 31 March 2012 (up to 31.4 months)
Secondary outcome [15] 0 0
Number of Participants With Non-Serious Adverse Events, Serious Adverse Events and Death - 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.
Timepoint [15] 0 0
Randomization until study completion (Until data cutoff= 09 Sep 2015 [up to 64 months])

Eligibility
Key inclusion criteria
Key

- newly diagnosed glioblastoma

- World Health Organization (WHO) performance status less than or equal to (<=2)

- stable or decreasing corticosteroid dose within 5 days prior to randomization

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- evidence of recent hemorrhage on postoperative magnetic resonance imaging (MRI) of
brain

- any prior chemotherapy or immunotherapy for glioblastomas and low grade astrocytomas

- any prior radiotherapy to brain

- clinically significant cardiovascular disease

- history of greater than or equal to (>=) grade 2 hemoptysis within 1 month prior to
randomization

- previous centralized screening for Methylguanine-DNA methyltransferase (MGMT) status
for enrollment into a clinical trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Prince of Wales Hospital; Department of Medical Oncology - Randwick
Recruitment hospital [2] 0 0
North Shore Private Hospital; Northern Specialist Centre - St Leonards
Recruitment hospital [3] 0 0
Royal North Shore Hospital; Department of Medical Oncology - St Leonards
Recruitment hospital [4] 0 0
Princess AleXandra Hospital; Department of Medical Oncology - Woolloongabba
Recruitment hospital [5] 0 0
Calvary North Adelaide; North Adeliade Oncology Centre - North Adelaide
Recruitment hospital [6] 0 0
Royal Melbourne Hospital; Hematology and Medical Oncology - Parkville
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles
Country [11] 0 0
Belgium
State/province [11] 0 0
Edegem
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Belgium
State/province [13] 0 0
Liège
Country [14] 0 0
Belgium
State/province [14] 0 0
Roeselare
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
British Columbia
Country [17] 0 0
Canada
State/province [17] 0 0
Manitoba
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Canada
State/province [20] 0 0
Saskatchewan
Country [21] 0 0
Denmark
State/province [21] 0 0
Aalborg
Country [22] 0 0
Denmark
State/province [22] 0 0
København Ø
Country [23] 0 0
Denmark
State/province [23] 0 0
Odense
Country [24] 0 0
France
State/province [24] 0 0
Bobigny
Country [25] 0 0
France
State/province [25] 0 0
Bordeaux
Country [26] 0 0
France
State/province [26] 0 0
Bron
Country [27] 0 0
France
State/province [27] 0 0
Clermont Ferrand
Country [28] 0 0
France
State/province [28] 0 0
Clichy
Country [29] 0 0
France
State/province [29] 0 0
Dijon
Country [30] 0 0
France
State/province [30] 0 0
Marseille
Country [31] 0 0
France
State/province [31] 0 0
Montpellier
Country [32] 0 0
France
State/province [32] 0 0
Nancy
Country [33] 0 0
France
State/province [33] 0 0
Paris
Country [34] 0 0
Germany
State/province [34] 0 0
Dresden
Country [35] 0 0
Germany
State/province [35] 0 0
Gießen
Country [36] 0 0
Germany
State/province [36] 0 0
Hamburg
Country [37] 0 0
Germany
State/province [37] 0 0
Heidelberg
Country [38] 0 0
Germany
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Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This 2 arm study investigated the efficacy and safety of the addition of bevacizumab to the
current standard of care (multimodality therapy of concurrent radiotherapy plus temozolomide
followed by adjuvant temozolomide) as compared to the current standard of care alone.
Participants were randomly assigned to either the bevacizumab (10 milligrams per kilogram
(mg/kg) intravenously [IV] once every 2 week [q2w]) or the placebo arm, in combination with
radiation therapy (total dose 60 Gray [Gy], administered as 2 Gy fractions, 5 days/week) plus
temozolomide (75 milligrams per meter squared [mg/m^2] oral administration [po] daily) for 6
weeks. After a 4 week treatment break, participants continued to receive bevacizumab (10
mg/kg IV q2w) or placebo, plus temozolomide (150-200 mg/m^2 po daily on days 1-5 of each 4
week cycle) for 6 cycles of maintenance treatment or until disease progression or
unacceptable toxicity, whichever occured first. Following the maintenance phase, bevacizumab
(15 mg/kg iv every 3 weeks [q3w]) or placebo monotherapy continued. The time on study
treatment was until disease progression.
Trial website
https://clinicaltrials.gov/show/NCT00943826
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications