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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00943826




Registration number
NCT00943826
Ethics application status
Date submitted
17/07/2009
Date registered
22/07/2009
Date last updated
25/09/2017

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
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

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.
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
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)
Timepoint [2] 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
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
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
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)
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
Timepoint [5] 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
Sex
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
29/06/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/09/2015
Sample size
Target
Accrual to date
Final
921
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
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United States of America
State/province [2] 0 0
California
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United States of America
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Colorado
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Florida
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Illinois
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Michigan
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Ohio
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Tennessee
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United States of America
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Virginia
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Belgium
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Bruxelles
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Belgium
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Edegem
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Belgium
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Gent
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Belgium
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Liège
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Belgium
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Roeselare
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Canada
State/province [15] 0 0
Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
State/province [18] 0 0
Ontario
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Canada
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Quebec
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Canada
State/province [20] 0 0
Saskatchewan
Country [21] 0 0
Denmark
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Aalborg
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Denmark
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København Ø
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Denmark
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Odense
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France
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Bobigny
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France
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Bordeaux
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France
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Bron
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France
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Clermont Ferrand
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France
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Clichy
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France
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Dijon
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France
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Marseille
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France
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Montpellier
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France
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Nancy
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France
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Paris
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Germany
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Dresden
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Germany
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Gießen
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Ibbenbühren
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Germany
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Mainz
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Germany
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München
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Greece
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Heraklion
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Greece
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Larissa
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Greece
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Thessaloniki
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Hong Kong
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Hong Kong
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Hungary
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Budapest
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Hungary
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Miskolc
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Hungary
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Pecs
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petach Tikva
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Israel
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Tel Hashomer
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Italy
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Emilia-Romagna
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Italy
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Lombardia
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Italy
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Piemonte
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Italy
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Umbria
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Italy
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Veneto
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Japan
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Hiroshima
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Japan
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Ibaraki
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Japan
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Kumamoto
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tokyo
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Korea, Republic of
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Busan
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Daegu
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Korea, Republic of
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Goyang-si
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Korea, Republic of
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Jeollanam-do
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Eindhoven
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Utrecht
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New Zealand
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Auckland
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New Zealand
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Christchurch
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New Zealand
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Hamilton
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Poland
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Bialystok
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Poland
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Bydgoszcz
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Poland
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Lublin
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Portugal
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Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Romania
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Bucharest
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Romania
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Cluj-napoca
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Romania
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Targu Mures
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Russian Federation
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Moscow
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Russian Federation
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St. Petersburg
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Valencia
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Sweden
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Göteborg
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Sweden
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Lund
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Sweden
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Umea
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Sweden
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Uppsala
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Switzerland
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Geneve
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United Kingdom
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Birmingham
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United Kingdom
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Bristol
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United Kingdom
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London
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United Kingdom
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Newcastle Upon Tyne
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United Kingdom
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Nottingham
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United Kingdom
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Romford
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United Kingdom
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Sheffield
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United Kingdom
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Sutton
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United Kingdom
State/province [102] 0 0
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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00943826