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Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Recurrent or Progressive Glioblastoma | Clinical Trials | Clareo Health

TERMINATEDPHASE2

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

NCT01122901•National Cancer Institute (NCI)

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have histologically proven glioblastoma which is progressive or recurrent following radiation therapy +/- chemotherapy
•Patients must have measurable contrast-enhancing progressive or recurrent glioblastoma by magnetic resonance imaging (MRI) imaging within two weeks of starting treatment; patient must be able to tolerate MRIs
•GROUP B PATIENTS ONLY: Patients must be eligible for surgical resection according to the following criteria:
•* Expectation that the surgeon can resect \>= 50% of the Gd-enhancing tumor with low risk of inducing neurological injury
•* Absence of hematologic, cardiac or other medical contraindications to surgery
•* Surgery must take place Monday-Thursday with the exception of patients being treated at Cleveland Clinic/University Hospitals: these patients may undergo surgery Monday-Friday
•* Patients must have a tumor size \>= 2.5 cm in diameter in two perpendicular planes in order to enable correlative studies
•* Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment)
•Patients may have an unlimited number of prior therapy regimens but no prior gamma-secretase inhibitors
•Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
+28 more criteria

Exclusion Criteria

•Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety, are ineligible
•Patients with prior treatment with gamma-secretase inhibitors are ineligible
•Patients may not be receiving any other investigational agents
•Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 or other agents used in the study are ineligible
•Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption are ineligible; patients must be able to swallow capsules
•Patients with the following cardiovascular abnormalities are ineligible: baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female)
•Patients with a requirement for antiarrhythmics or other medications known to prolong QTc are ineligible
•Patients with a history of being serologically positive for hepatitis B or C, or who have a history of cirrhosis are ineligible
•Patients with a history of uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
•Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, a history of torsades de pointes or other significant cardiac arrhythmias other than chronic stable atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
+2 more criteria

Locations (5)

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

Henry Ford Hospital

Detroit, Michigan, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Key Dates

Start Date

December 1, 2010

Primary Completion Date

August 1, 2015

Completion Date

August 1, 2015

Last Updated

May 3, 2017

Enrollment

ACTUAL participants

Conditions

Adult Giant Cell GlioblastomaAdult GlioblastomaAdult GliosarcomaRecurrent Adult Brain Tumor

Interventions

gamma-secretase/Notch signalling pathway inhibitor RO4929097

DRUG

therapeutic conventional surgery

PROCEDURE

pharmacological study

OTHER

laboratory biomarker analysis

OTHER

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COMPLETEDPHASE2

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 3, 2017Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Advanced MR Imaging as Predictor of Treatment Response in Newly Diagnosed Glioblastomas

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