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

Roche

Status and phase: Completed; Phase 3

Conditions: Glioblastoma

Treatments: Radiation: Radiation therapy; Drug: Temozolomide; Drug: Placebo; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00943826

2008-006146-26 (EudraCT Number)

BO21990

Details and patient eligibility

About

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.

Enrollment: 921 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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921 participants in 2 patient groups, including a placebo group

Bevacizumab + RT + Temozolomide

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: Bevacizumab

Radiation: Radiation therapy

Placebo + RT + Temozolomide

Placebo Comparator group

Description:

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:

Drug: Temozolomide

Drug: Placebo

Radiation: Radiation therapy