A Phase II and Pharmacodynamic Trial of RO4929097 for Patients With Recurrent/Progressive Glioblastoma

Status
Active
Cancer Type
Brain Cancer
Trial Phase
Phase II
Eligibility
18 and over, Male and Female
Study Type
Biomarker/Laboratory analysis
Treatment
NCD ID
NCT01122901
Protocol IDs
CDR0000672628 (primary)
U01CA137443
ABTC-0906
Study Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Summary

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.

Objectives

OBJECTIVES:

Primary

  • 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)

Secondary

  • 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.