Clinical trial NCT01290263
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma GBM Brain Tumor Glioma
Sponsor: Dana-Farber Cancer Institute
Start date: 2010-12-01; Completion date: 2017-01-01
Enrollment: 48 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief 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 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.

Detailed description:

Arms: arm 1: Cohort A will assess recurrent Glioblastoma Multiforme (GBM) patients who receive AMG 386 monotherapy at 30mg/kg every week. As of August 1, 2013, Cohort A was closed to new accrual following early interim analysis of first 10 participants enrolled on study. None of these patients had achieved stable disease or response at their initial evaluation after 1-2 months of study therapy. Therefore, study investigators and sponsor agreed that the level of single-agent anti-tumor activity associated with AMG386 for recurrent glioblastoma patients is most likely insufficient to satisfy the stopping rule for low efficacy outlined in Section 14.5 for Cohort A. arm 2: Cohort B will assess recurrent Glioblastoma Multiforme(GBM) patients who receive AMG 386 plus bevacizumab. Because the maximum tolerated dose of this combination therapy has not yet been established, a 3x3 Phase I study was used to determine the maximum tolerated dose. As of June 6, 2014, the MTD was determined to be AMG386 30 mg/kg administered intravenously every week(dose level +1) in combination with bevacizumab at 10mg/kg administered intravenously every other week. As of July 25, 2014 the Cohort B, Phase II portion of the study was opened to accrual.
Interventions: intervention 1: Amgen 386 intervention 2: Bevacizumab
Intervention descriptions: intervention 1: For Cohort A, AMG 386 will be administered intravenously at 30 mg/kg every week.

For Cohort B Phase I, AMG 386 will be administered intravenously at beginning at starting dose level of 15 mg/kg every week.

For Cohort B Phase II, AMG 386 will be administered intravenously at the maximum tolerated dose determined in the Phase I portion of the study every week. intervention 2: The dose of bevacizumab will be 10 mg/kg and will be administered intravenously every other week.

Protocol documents: