Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of AMG 386 (trebananib) 15 mg/kg weekly in
combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1). (closed to accrual 10/2/12)
II. To assess the efficacy of AMG 386 in combination with bevacizumab 10 mg/kg every 2 weeks
compared to bevacizumab monotherapy in bevacizumab-naïve patients, as measured by 6-month
progression-free survival (PFS6) (Cohort 2).
SECONDARY OBJECTIVES:
I. To further assess the toxicity profile (Cohorts 1 and 2). II. To assess feasibility of
AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1
[closed to accrual 10/2/12]), as measured by the percentage of patients requiring dose
reduction/interruption or discontinuation in the first 2 and subsequent cycles.
III. To determine the radiographic response rate (RR), median progression-free survival
(PFS), and overall survival (OS) in bevacizumab-naïve patients (Cohort 2).
IV. To assess the efficacy of AMG 386 15 mg/kg weekly in combination with bevacizumab 10
mg/kg every 2 weeks in patients who have progressed while on bevacizumab, as measured by
overall survival (OS) (cross-over from placebo arm of Cohort 2).
V. To correlate outcome to treatment with tumor genotype, expression profile, and
circulating angiogenesis biomarkers in tumor specimens (Cohort 2).
VI. To determine the RR, PFS6, and PFS in patients who have progressed while on bevacizumab
therapy and receive AMG 386 in combination with bevacizumab (cross-over from placebo arm of
Cohort 2).
VII. To determine the serum pharmacokinetics of AMG 386 in patients receiving bevacizumab
(Cohort 1 and cross-over from placebo arm of Cohort 2).
OUTLINE: This is a safety study (cohort 1 [closed to accrual 10/2/12]) followed by a
randomized study (cohort 2).
Cohort 1: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and
15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity. (closed to accrual
10/2/12)
Cohort 2: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive bevacizumab and trebananib as in Cohort 1.
ARM II: Patients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days
1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity. Patients with disease progression may cross over to Arm I.
After completion of study treatment, patients are followed up at 30 days, every 2 months for
1 year, every 6 months for 1 year, and then annually thereafter.
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