RATIONALE: RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II clinical trial is studying how well RO4929097 works in treating patients with recurrent or progressive glioblastoma.
- To determine 6-month progression-free survival (PFS) of patients with recurrent or progressive glioblastoma treated with gamma-secretase inhibitor RO4929097. (Group A)
- To determine the efficiency of neurosphere generation after pretreatment with gamma-secretase inhibitor RO4929097. (Group B)
- To determine radiographic response rate. (Group A)
- To determine toxicities associated with this treatment. (Group A and B)
- To determine overall survival. (Group A and B)
- To determine the expression levels of Notch pathway components and downstream targets. (Group B)
- To determine tumor propagation (an extension of lifespan by 50% in tumor-bearing mice). (Group B)
- To determine patient event-free survival in correlation with expression levels of Notch pathway components and downstream targets. (Group B)
- To determine 6-month PFS. (Group B)
OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups.
- Group A: Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Group B (surgical resection indicated): Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days -6 to -1. Patients undergo surgical resection on day 0. Within 30 days after surgical resection, patients receive gamma-secretase inhibitor RO4929097 as in group A.
Tumor tissue from the initial diagnosis (before any treatment) and from surgical re-resection and pre- and post-surgery plasma samples are collected from patients in group B for pharmacokinetic and correlative studies.
After completion of study treatment, patients are followed up every 2 months.
PROJECTED ACCRUAL: A total of 60 patients (40 patients in group A and 20 patients in group B) will be accrued for this study.