Overview

This trial is active, not recruiting.

Condition glioblastoma
Treatments bevacizumab [avastin®], placebo, temozolomide, radiation therapy
Phase phase 3
Sponsor Hoffmann-La Roche
Start date June 2009
End date March 2012
Trial size 921 participants
Trial identifier NCT00943826, 2008-006146-26, BO21990

Summary

This 2 arm study investigated the efficacy and safety of the addition of bevacizumab (Avastin®) 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. Patients were randomly assigned to either the Avastin® (10 mg/kg iv q2w) or the placebo arm, in combination with radiation therapy (total dose 60 Gy, administered as 2 Gy fractions, 5 days/week)plus temozolomide (75 mg/m2 po daily) for 6 weeks. After a 4 week treatment break, patients continued to receive Avastin® (10 mg/kg iv q2w) or placebo, plus temozolomide (150-200 mg/m2 po daily on days 1-5 of each 4 week cycle) for 6 cycles of maintenance treatment. Following the maintenance phase, Avastin® (15 mg/kg iv q3w) or placebo monotherapy was continued. The anticipated time on study treatment was until disease progression/unacceptable toxicity.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
In the Concurrent Phase participants received radiotherapy (RT) in daily fractions of 2 Gy given 5 days per week for 6 week and temozolomide 75 mg/m^2 daily for a maximum of 49 days 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.
bevacizumab [avastin®]
10 mg/kg intravenously every 2 weeks in the Concurrent and Maintenance Phases. 15 mg/kg intravenously every 3 weeks in the Monotherapy Phase.
temozolomide
75 mg/m2 once daily for 6 weeks, followed by 150-200 mg/m2 once daily on days 1-5 of each 6 x 4 week cycle.
radiation therapy
30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks
(Placebo Comparator)
In the Concurrent Phase participants received radiotherapy in daily fractions of 2 Gy given 5 days per week for 6 week and temozolomide 75 mg/m^2 daily for a maximum of 49 days 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.
placebo
Intravenously every 2 weeks in the Concurrent and Maintenance Phases and every 3 weeks in the Monotherapy Phase.
temozolomide
75 mg/m2 once daily for 6 weeks, followed by 150-200 mg/m2 once daily on days 1-5 of each 6 x 4 week cycle.
radiation therapy
30 fractions of 2 Gy delivered on days 1-5 per week for 6 weeks

Primary Outcomes

Measure
Co-Primary: Progression-free Survival (PFS) as Assessed by Investigator
time frame: Randomization until Progressive Free Survival Event [Until data cutoff= 31 March 2012 (up to 34 months)]
Co-Primary: Overall Survival (OS)
time frame: Randomization until Overall Survival Event

Secondary Outcomes

Measure
Progression-free Survival (PFS) as Assessed by an Independent Review Facility
time frame: Randomization until Progressive Free Survival Event [Until data cutoff= 31 March 2012 (up to 34 months)]
Percentage of Participants With One-Year Survival
time frame: 1 year
Percentage of Participants With Two-year Survival
time frame: 2 years
Duration of Stable/Improved Health Related Quality of Life (HRQoL) Using the European Organisation for Research and Treatment of Cancer Scales (EORTC) QLQ-C30 and BN20
time frame: Randomization until Progressive Free Survival Event [Until data cutoff= 31 March 2012 (up to 34 months)]
Number of Participants With Adverse Events, Serious Adverse Events and Death
time frame: Until data cutoff= 31 March 2012 (up to 34 months)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - adult patients, >=18 years of age; - newly diagnosed glioblastoma; - World Health Organization (WHO) performance status <=2; - stable or decreasing corticosteroid dose within 5 days prior to randomization. Exclusion Criteria: - evidence of recent hemorrhage or 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 >=grade 2 hemoptysis within 1 month prior to randomization; - previous centralized screening for Methylguanine-DNA methyltransferase (MGMT) status for enrollment into a clinical trial.

Trial information was received from ClinicalTrials.gov and was last updated in September 2013.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.