NCT01122901

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Recurrent or Progressive Glioblastoma

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial is studying how well gamma-secretase/Notch signalling pathway inhibitor RO4929097 works in treating patients with recurrent or progressive glioblastoma. Gamma-secretase/Notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. 6-month progression-free survival (PFS6). (Group A) II. Efficiency of neurosphere generation after pretreatment with RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097). (Group B) SECONDARY OBJECTIVES: I. Radiographic response rate. (Group A) II. Toxicities associated with this regimen. (Group A) III. Overall survival. (Group A) IV. Expression levels of Notch pathway components and downstream targets. (Group B) V. Tumor propagation. An extension of lifespan by 50% in tumor bearing mice (mice bearing fresh tumor tissue). (Group B) VI. Patient event-free survival in correlation with expression levels of Notch pathway components and downstream targets. VII. 6-month progression-free survival (PFS6). VIII. Toxicities associated with this regimen. IX. Overall survival. OUTLINE: Patients are assigned to 1 of 2 treatment groups. GROUP A: Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 orally (PO) once daily (QD) 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 gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days -6 to -1. Patients undergo surgical resection on day 0. Within 30 days after surgical resection, patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 as in Group A. After completion of study treatment, patients are followed up every 2 months.

Conditions

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Recurrent Adult Brain Tumor

Interventions

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

Timeline

• Start date: 2010-12-01
• Primary completion: 2015-08-01
• Completion: 2015-08-01
• First posted: 2010-05-13
• Last updated: 2017-05-03
• Results posted: 2017-05-03

Locations

5 sites across 1 country: United States