RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma
This phase I trial studies the side effects and best dose of gamma-secretase/Notch signalling pathway inhibitor RO4929097 (RO4929097) when given together with temozolomide and radiation therapy in treating patients with newly diagnosed malignant glioma. Enzyme inhibitors, such as gamma-secretase/Notch signalling pathway inhibitor RO4929097, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving gamma-secretase/Notch signalling pathway inhibitor RO4929097 together with temozolomide and radiation therapy may kill more tumor cells.
Adult Anaplastic (Malignant) Meningioma
Adult Anaplastic Astrocytoma
Adult Anaplastic Ependymoma
Adult Brain Stem Glioma
Adult Choroid Plexus Neoplasm
Adult Diffuse Astrocytoma
Adult Giant Cell Glioblastoma
Adult Grade I Meningioma
Adult Grade II Meningioma
Adult Mixed Glioma
Adult Myxopapillary Ependymoma
Adult Papillary Meningioma
Adult Pilocytic Astrocytoma
Adult Pineal Gland Astrocytoma
Adult Primary Melanocytic Lesion of Meninges
Adult Subependymal Giant Cell Astrocytoma
Adult Supratentorial Primitive Neuroectodermal Tumor
Malignant Adult Intracranial Hemangiopericytoma
Drug: Gamma-Secretase Inhibitor RO4929097
Procedure: Therapeutic Conventional Surgery
Radiation: Intensity-Modulated Radiation Therapy
Radiation: 3-Dimensional Conformal Radiation Therapy
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Trial of RO4929097 in Combination With Standard Radiotherapy and Temozolomide for Newly Diagnosed Malignant Glioma: A Pharmacokinetic and Pharmacodynamic Study|
- Maximum-tolerated dose defined as the highest dose studied for which the incidence of dose limiting toxicity is less than 33% using National Cancer Institute Common Toxicity Criteria [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]The percentage of patients who experience toxicity at each dose level will be calculated, with a 95% confidence interval.
- Pharmacokinetic (PK) parameters of gamma-secretase/Notch signalling pathway inhibitor RO4929097 [ Time Frame: Pre-dose, 30 minutes, 1, 2, 4, 6, and 8 hours ] [ Designated as safety issue: No ]Noncompartmental and/or compartmental methods will be used to calculate PK parameters of gamma-secretase/Notch signalling pathway inhibitor RO4929097 and temozolomide from the plasma concentration-time data collected from each individual. Descriptive statistics (including number, mean and/or median, standard deviation, coefficient of variation, and range) for PK parameters will be tabulated by dose level.
- Changes in MRI parameters [ Time Frame: Baseline to up to 4 years ] [ Designated as safety issue: No ]Perfusion and diffusion-based MRI parameters including but not restricted to blood volume, mean and median apparent diffusion coefficient and structural volumes will be analyzed. Results will be summarized, and mean and median values at different time points will be tabulated. Changes in such parameters will be checked for statistical significance and correlated with the disease status.
- Percent changes in serum YKL-40 levels and hair follicle HES1 levels [ Time Frame: Baseline to up to 4 years ] [ Designated as safety issue: No ]Means and medians of all patients together will be calculated and tabulated for each time point, with depiction of standard deviations. A Wilcoxon test will be used to determine p value of changes in mean values of YKL-40 and hairy and enhancer of split 1, (Drosophila) (HES1), with a p value of less than 0.05 considered statistically significant.
- Expression of a variety of proteins through immunohistochemistry and/or real time quantitative polymerase chain reaction and tumor tissue culture [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Analyses will include comparison of results before and after exposure to gamma-secretase/Notch signalling pathway inhibitor RO4929097 (Wilcoxon rank sum test), as well as status of the Notch pathway and cancer stem cells in a control population of 20 untreated patients (Mann Whitney test).
|Study Start Date:||May 2010|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (RO4929097, surgery, radiation therapy)
See Detailed Description.
Drug: Gamma-Secretase Inhibitor RO4929097
Other Name: RO4929097Procedure: Therapeutic Conventional Surgery
Undergo surgeryRadiation: Intensity-Modulated Radiation Therapy
Other Names:Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3-D conformal radiation therapy
Other Names:Drug: Temozolomide
Other Name: TMZOther: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01119599
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Antonio Omuro||Memorial Sloan Kettering Cancer Center.|