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

Stopped early · Phase 2

Conditions studied: Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

In brief

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.

Key facts

Study ID: NCT01122901
Run by: National Cancer Institute (NCI)
People needed: 47
Starts: 2010-12-01
Expected to finish: 2015-08-01
Last updated by the study team: 2017-05-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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:
3 months from the completion of radiation
6 weeks from a nitrosourea chemotherapy
3 weeks from a non-nitrosourea chemotherapy
4 weeks from any investigational (not Food and Drug Administration [FDA]-approved) agents
2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., small molecule targeted therapy, thalidomide, bevacizumab, etc.)
Patients may not be on an enzyme-inducing anti-epileptic drug (EIAED); if previously on an EIAED, patient must be off for at least 14 days prior to the first dose of RO4929097
Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
Hemoglobin >= 9 g/dL
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
Total bilirubin =< institutional upper limit of normal
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 4.0 x institutional upper limit of normal
Creatinine within institutional upper limit of normal OR
Creatinine clearance >= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
Electrolytes - calcium, chloride, magnesium, potassium, phosphorus, sodium within institutional normal limits

You may not qualify if…

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
Pregnant women or those who are breastfeeding are ineligible
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Patients who have not recovered to < Common Terminology Criteria for Adverse Events (CTCAE) grade 2 toxicities related to prior therapy are not eligible to participate in this study

Where it is running

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

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.