Amgen 386 for Recurrent Glioblastoma

Study Summary

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 t

Primary Outcome

PFS6 is the proportion of patients remaining alive and progression-free at 6-months from study entry. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010). RANO criteria has 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown status. CR: disappearance of all enhancing lesions, stable or improved non-enhancing lesions, and stable or improved clinically. P

Interventions

• DRUG Bevacizumab
• DRUG Amgen 386