RO4929097and Bevacizumab in Treating Patients With Progressive or Recurrent Malignant Glioma

Adult Glioblastoma Clinical Trial

Official title: Phase I/II Study of R04929097 With Bevacizumab in Patients With Recurrent Malignant Glioma

Status Terminated

Clinical Trial Summary

This phase I/II trial is studying the side effects and the best dose of RO4929097 to see how well it works when given together with bevacizumab compared to bevacizumab alone in treating patients with progressive or recurrent malignant glioma. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving RO4929097 together with bevacizumab may kill more tumor cells.

Clinical Trial Description

Phase I

Primary Objective:

1. To assess the safety profile of R04929097 in combination with bevacizumab and to determine a recommended Phase II dose of R04929097 in combination with bevacizumab in patients with recurrent malignant glioma

Secondary Objectives:

2. To describe the toxicity associated with this combination regimen

3. To assess pharmacokinetics of R04929097 in combination with bevacizumab

Phase II I. Assess the safety profile and the recommended phase II dose of gamma-secretase inhibitor RO4929097 (RO4929097) in combination with bevacizumab in patients with recurrent malignant glioma.

II. Assess the progression-free survival at 6 months of patients treated with this regimen.

III. Compare the overall survival of patients with recurrent glioblastoma treated with RO4929097 and bevacizumab versus bevacizumab alone.

SECONDARY OBJECTIVES:

I. Describe the toxicity associated with this regimen in these patients. II. Assess the pharmacokinetics of this regimen in these patients. III. Estimate the proportion of patients alive and progression-free survival at 6 months in patients treated with RO4929097 and bevacizumab versus bevacizumab alone.

IV. Evaluate the safety and tolerability of these regimens in these patients. V. Explore potential prognostic biomarkers from glioma tissue at baseline and potential association with Notch pathway inhibition.

OUTLINE: This is a multicenter, phase I, dose-escalation study of gamma-secretase inhibitor RO4929097 (RO4929097) followed by a randomized phase II study.

PHASE I: Patients receive oral RO4929097 on days 1-3, 8-10, 15-17, and 22-24, and bevacizumab IV over 30-90 minutes on days 1 and 15 (days 2 or 3 and 15 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized* to 1 of 2 treatment arms.

ARM I: Patients receive oral RO4929097 on days 1-3, 8-10, 15-17, and 22-24, and bevacizumab IV over 30-90 minutes on days 1 and 15.

ARM II: Patients receive bevacizumab as in arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *If phase II single-arm study demonstrates effectiveness, it will proceed to the phase II randomized study.

Some patients undergo blood sample collection for pharmacokinetic studies. Archived tumor tissue samples are analyzed for potential biomarkers and Notch pathway inhibition.

After completion of study therapy, patients are followed up every 2 months. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Anaplastic Astrocytoma
• Adult Anaplastic Oligodendroglioma
• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Astrocytoma
• Glioblastoma
• Gliosarcoma
• Oligodendroglioma
• Recurrent Adult Brain Tumor

• NCT number: NCT01189240
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 2010
• Completion date: February 2015