Phase I/II Study of R04929097 With Bevacizumab in Patients With Recurrent Malignant Glioma
I. Assess the safety profile and the recommended phase II dose of gamma-secretase inhibitor
RO4929097 (RO4929097) in combination with bevacizumab in patients with recurrent malignant
II. Assess the progression-free survival at 6 months of patients treated with this regimen.
III. Compare the overall survival of patients with recurrent glioblastoma treated with
RO4929097 and bevacizumab versus bevacizumab alone.
I. Describe the toxicity associated with this regimen in these patients. II. Assess the
pharmacokinetics of this regimen in these patients. III. Estimate the proportion of patients
alive and progression-free survival at 6 months in patients treated with RO4929097 and
bevacizumab versus bevacizumab alone.
IV. Evaluate the safety and tolerability of these regimens in these patients. V. Explore
potential prognostic biomarkers from glioma tissue at baseline and potential association
with Notch pathway inhibition.
OUTLINE: This is a multicenter, phase I, dose-escalation study of gamma-secretase inhibitor
RO4929097 (RO4929097) followed by a randomized phase II study.
PHASE I: Patients receive oral RO4929097 on days 1-3, 8-10, 15-17, and 22-24, and
bevacizumab IV over 30-90 minutes on days 1 and 15 (days 2 or 3 and 15 of course 1 only).
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized* to 1 of 2 treatment arms.
ARM I: Patients receive oral RO4929097 on days 1-3, 8-10, 15-17, and 22-24, and bevacizumab
IV over 30-90 minutes on days 1 and 15.
ARM II: Patients receive bevacizumab as in arm I.
In both arms, courses repeat every 28 days in the absence of disease progression or
NOTE: *If phase II single-arm study demonstrates effectiveness, it will proceed to the phase
II randomized study.
Some patients undergo blood sample collection for pharmacokinetic studies. Archived tumor
tissue samples are analyzed for potential biomarkers and Notch pathway inhibition.
After completion of study therapy, patients are followed up every 2 months.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose and the recommended phase II dose of gamma-secretase inhibitor RO4929097 in combination with bevacizumab determined by dose-limiting toxicity rate (Phase I)
National Cancer Institute (NCI)
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Adult Brain Tumor Consortium||Baltimore, Maryland 21231-1000|