NCT01269411

RO4929097 in Treating Patients With Recurrent Invasive Gliomas

Phase I Pharmacodynamic and "High Content" Study of the Gamma-Secretase Inhibitor RO4929097 in Patients With Recurrent Malignant Gliomas (MGs) Targeting p75NTR to Inhibit Brain Tumor Initiating Cells (BTICs) and Recurrent Invasive Gliomas

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of RO4929097 in treating patients with recurrent invasive gliomas. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed description

PRIMARY OBJECTIVES: I. Determine, in patients with recurrent MGs (many of whom receive dexamethasone, a moderate CYP3A4 inducer), the safety and maximum-tolerated dose of RO4909297 administered at 2 dose levels. II. Determine the pharmacokinetics, intratumoral drug concentration, target modulation, and evidence of any treatment effect in the malignant glioma tumor tissue by R04929097 administered at the dose found in Part A. SECONDARY OBJECTIVES: I. Determine the pharmacokinetic (PK) profile of RO4909297 in patients with recurrent MGs (many of whom receive dexamethasone, a moderate CYP3A4 inducer). II. Determine the progression-free survival of patients with recurrent malignant glioma following treatment with R04929097. III. Determine if the RPTD dose of RO4929097 significantly inhibits p75\^NTR cleavage and processing. IV. Determine the effects of RO4929097 on the establishment and growth of BTIC cultures in neurosphere growth conditions, effects on proliferation, ability to self-renewal, and ability to differentiate along lineage-specific pathways. V. Determine the ability of RO4929097 to inhibit Notch signaling, by assessing downstream target activation, in glioma tissue of patients with recurrent MG. VI. Determine the association between a number of serum, tumor, and BTIC markers and response to R04929097. OUTLINE: This is a multicenter, dose-escalation (part A) study followed by an open-label (part B) study. PART A: Patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. PART B: Patients receive oral RO4929097 once daily on days 1-7 and undergo surgery on day 8. Beginning 28 days later, patients receive oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Post resection tumor specimens are collected for correlative studies, including pharmacokinetic and biomarker assays. After completion of study therapy, patients are followed up at 30 days and then every 3 month for up to 6-12 months.

Conditions

• Adult Anaplastic Oligodendroglioma
• Adult Brain Stem Glioma
• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Adult Mixed Glioma
• Recurrent Adult Brain Tumor

Interventions

Type	Name	Description
DRUG	gamma-secretase/Notch signalling pathway inhibitor RO4929097	Given orally
PROCEDURE	therapeutic conventional surgery	Undergo surgery
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative

Timeline

• Start date: 2011-07-01
• Primary completion: 2012-02-01
• First posted: 2011-01-04
• Last updated: 2013-02-07

Locations

1 site across 1 country: Canada