Phase II Trial of Avastin Plus Bortezomib for Patients With Recurrent Malignant Glioma
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 will be enrolled in study. Avastin
administered intravenously at dose 15 mg/kg every 3 weeks. Bortezomib administered on day 1,
4, 8, 11, 22, 25, 29, & 32 of 42-day cycle. Dose of bortezomib will be 1.7 mg/m2 for
non-EIAED patients & 2.5 mg/m2 for EIAED patients. Treatment will continue until either
evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up
/ withdrawal of consent. Brain MRIs will be 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 < are considered desirable, while rates of 40 percent or > are
considered as undesirable. Statistical hypothesis that needs testing differentiates between
15% & 40% rate of unacceptable toxicity.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
6 month progression-free survival among patients receiving EIAED and patients not receiving EIAED.
6 - 9 months
Katherine B Peters, MD
Duke University Health System
United States: Institutional Review Board
|Duke University Health System||Durham, North Carolina 27705|