Clinical trial NCT00611325
Conditions: Glioblastoma Gliosarcoma
Keywords: Glioblastoma Gliosarcoma Glioblastoma multiforme Recurrent malignant glioma GBM Recurrent GBM Malignant glioma Brain tumor Avastin Bevacizumab Bortezomib Velcade
Sponsor: Duke University
Start date: 2008-05-01; Completion date: 2013-10-01
Enrollment: 56 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary Objective To estimate 6-month progression free survival probability of patients with recurrent glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs and non enzyme-inducing anti-epileptic drugs.

Secondary Objectives To evaluate safety \& tolerability of bortezomib plus Avastin among patients with recurrent malignant glioma.

To evaluate radiographic response, progression free survival \& overall survival of patients with recurrent malignant glioma treated with bortezomib plus Avastin

Detailed description:
This is an open-label, 2-arm Phase II study assessing safety \& efficacy of bortezomib in combination with Avastin for patients with recurrent glioblastoma multiforme (gbm). 56 total patients with recurrent WHO grade IV malignant gliomas have been enrolled on study. Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, \& 32 of a 42-day cycle. The dose of bortezomib was 1.7 mg/m2 for non-EIAED patients \& 2.5 mg/m2 for EIAED patients. Treatment continued until either evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up / withdrawal of consent. Brain MRIs were obtained after every cycle.

Bortezomib administration is associated with mild toxicity in most patients, such as fatigue, diarrhea \& nausea, constipation \& peripheral neuropathy. Less common, bortezomib administration leads to more significant hematologic toxicities \& peripheral neuropathies. Most significant toxicities associated with Avastin in recently completed phase II clinical trial at Duke were thrombotic complications \& grade 2 proteinuria. "Unacceptable" toxicities rates of 15 percent or less were considered desirable, while rates of 40 percent or greater were considered undesirable. The statistical hypothesis that needed testing differentiated between 15% \& 40% rate of unacceptable toxicity.

Arms: arm 1: Patients taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 2.5 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle. arm 2: Patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 1.7 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle.
Interventions: intervention 1: Avastin intervention 2: Bortezomib
Intervention descriptions: intervention 1: Avastin was administered intravenously at the dose 15 mg/kg every 3 weeks. intervention 2: Bortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, \& 32 of a 42-day cycle. Bortezomib was 1.7 mg/m2 for patients not taking EIAEDs \& 2.5 mg/m2 for patients taking EIAEDs.

Protocol documents: