Amgen 386 for Recurrent Glioblastoma
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).
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.
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.
Drug: Amgen 386
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Amgen 386 With and Without Bevacizumab for Recurrent Glioblastoma|
- Radiological response rates [ Time Frame: 6 month ] [ Designated as safety issue: No ]The primary outcome is 6 month progression-free survival. The primary basis for assessing efficacy will be the proportion of patients who survive 6 months without disease progression (PFS-6).
- Radiographic response and Median progression free survival and overall survival. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]Median progression free survival and overall survival. The primary measure of safety outcome will include a tabulation of all grade 2 or greater, treatment related toxicities.
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Amgen 386
Cohort A will assess recurrent Glioblastoma Multiforme (GBM) patients who receive AMG 386 monotherapy. For each cohort, AMG 386 will be administered intravenously at 15 mg/kg every week. The dose of bevacizumab will be 10 mg/kg and will be administered intravenously every other 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.
Drug: Amgen 386
For each cohort, AMG 386 will be administered intravenously at 15 mg/kg every week.
Experimental: Amgen 386 and Bevacizumab
Cohort B will assess recurrent Glioblastoma Multiforme(GBM) patients who receive AMG 386 plus bevacizumab. For each cohort, AMG 386 will be administered intravenously at 15 mg/kg every week. The dose of bevacizumab will be 10 mg/kg and will be administered intravenously every other week.
Drug: Amgen 386
For each cohort, AMG 386 will be administered intravenously at 15 mg/kg every week.Drug: Bevacizumab
The dose of bevacizumab will be 10 mg/kg and will be administered intravenously every other week.
Other Name: Avastin
|Contact: David Reardon, M.D.||firstname.lastname@example.org|
|United States, California|
|University of California Los Angeles||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Emese Filka 310-794-3521 email@example.com|
|Principal Investigator: Timothy Cloughesy, MD|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Lisa Doherty, N.P. 617-632-5925 Lisa_Doherty@dfci.harvard.edu|
|Contact: Julee Pulverenti, P.A. 617-632-5749 JPulverenti@partners.org|
|Principal Investigator: David A. Reardon, MD|
|Massachusetts General Hosptial||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Edwin Nunez 617-643-4395 firstname.lastname@example.org|
|Principal Investigator: Elizabeth R. Gerstner, MD, MMSc|
|University of Massachusetts, Worcester||Recruiting|
|Worcester, Massachusetts, United States|
|Contact: Barbara Butler, RN 508-856-1956 Barbara.Butler@umassmemorial.org|
|Principal Investigator: Shakeeb Yunus, MD|
|United States, New York|
|New York - Presbyterian/Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Francine Armentano, NP, NP 212-305-5969 email@example.com|
|Principal Investigator: Andrew B. Lassman, MD|
|Sub-Investigator: Fabio Iwamoto, MD|
|United States, Virginia|
|University of Virginia||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Monika Thielen 434-243-9900 MJT3C@hscmail.mcc.virginia.edu|
|Principal Investigator: David Schiff, MD|
|Principal Investigator:||David Reardon, MD||Dana-Farber Cancer Institute|