Bevacizumab With or Without Trebananib in Treating Patients With Recurrent Brain Tumors

Glioblastoma Clinical Trial

Official title: Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma

Status Completed

Clinical Trial Summary

This partially randomized phase II trial with a safety run-in component studies the side effects and how well bevacizumab given with or without trebananib works in treating patients with brain tumors that have come back (recurrent). Immunotherapy with monoclonal antibodies, such as bevacizumab, may induce changes in the body's immune system and interfere with the ability of tumor cells to grow and spread. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together with trebananib is more effective than bevacizumab alone in treating brain tumors.

Clinical Trial Description

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-naive 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-naive 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. ;

Related Conditions & MeSH terms

• Brain Neoplasms
• Giant Cell Glioblastoma
• Glioblastoma
• Gliosarcoma
• Oligodendroglioma
• Recurrence
• Recurrent Brain Neoplasm
• Recurrent Glioblastoma

• NCT number: NCT01609790
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 2
• Start date: June 4, 2012
• Completion date: May 20, 2022