Primary Objectives
Cohort A -- monotherapy:
To determine the efficacy of AMG 386 in participants with recurrent glioblastoma (GBM) as
measured by 6-month progression-free survival (PFS6)
Cohort B - combination therapy:
Phase I To determine the maximum tolerated dose of AMG 386 in combination with bevacizumab
given at 10mg/kg every 2 weeks in participants with recurrent glioblastoma.
Phase II To determine the efficacy of AMG 386 plus bevacizumab in participants with recurrent
glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6).
Secondary Objectives:
To evaluate radiographic response in both cohort populations. To evaluate overall survival in
both cohort populations. To assess time-to-progression in both cohort populations. To
investigate the safety profile in both cohort populations.
Exploratory Objectives:
To evaluate expression of factors associated with tumor angiogenesis using a multiples
cytokine assay among participants undergoing therapy with AMG 386 with response to therapy
and development of resistance.
This is an open-label Phase I/II study of AMG 386 monotherapy and AMG 386 in combination with
bevacizumab. Two cohorts will accrue and will be assessed sequentially. Each cohort will
enroll participants with recurrent GBM. Cohort A will assess recurrent GBM participants who
receive AMG 386 monotherapy at 30 g/kg every week. (Cohort A initially accrued at a dose of
15mg/kg, but this was increased to 30 mg/kg every week following an amendment). Cohort B will
assess recurrent GBM participants who receive weekly AMG 386 plus bi-weekly bevacizumab
(10mg/kg). Cohort B will start with a Phase I component to determine the MTD of AMG 386 that
is safe when used in combination with bevacizumab. AMG 386 is administered intravenously,
and, when used in combination with intravenous bevacizumab, will be administered first.
Patients will be required to come to the clinic weekly for study drug administration.
For study purposes, a cycle of therapy will be 4 weeks. Treatment will continue until either
evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up,
or withdrawal of consent.
The estimated rate of accrual is 60 participants per year. The estimated date of accrual
completion is 1.5 years from study initiation. The estimated date of study completion will be
approximately 12 months from enrollment of the last study participant.