RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma
|ClinicalTrials.gov Identifier: NCT01119599|
Recruitment Status : Completed
First Posted : May 7, 2010
Last Update Posted : September 29, 2015
|Condition or disease||Intervention/treatment||Phase|
|Acoustic Schwannoma Adult Anaplastic (Malignant) Meningioma Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma Adult Brain Stem Glioma Adult Choroid Plexus Neoplasm Adult Craniopharyngioma Adult Diffuse Astrocytoma Adult Ependymoblastoma Adult Ependymoma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Grade I Meningioma Adult Grade II Meningioma Adult Medulloblastoma Adult Mixed Glioma Adult Myxopapillary Ependymoma Adult Oligodendroglioma Adult Papillary Meningioma Adult Pilocytic Astrocytoma Adult Pineal Gland Astrocytoma Adult Pineoblastoma Adult Pineocytoma Adult Primary Melanocytic Lesion of Meninges Adult Subependymal Giant Cell Astrocytoma Adult Subependymoma Adult Supratentorial Primitive Neuroectodermal Tumor Malignant Adult Intracranial Hemangiopericytoma||Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Gamma-Secretase Inhibitor RO4929097 Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Temozolomide Procedure: Therapeutic Conventional Surgery||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Trial of RO4929097 in Combination With Standard Radiotherapy and Temozolomide for Newly Diagnosed Malignant Glioma: A Pharmacokinetic and Pharmacodynamic Study|
|Study Start Date :||May 2010|
|Actual Primary Completion Date :||June 2013|
Experimental: Treatment (RO4929097, surgery, radiation therapy)
See Detailed Description.
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3-D conformal radiation therapy
Drug: Gamma-Secretase Inhibitor RO4929097
Other Name: RO4929097
Radiation: Intensity-Modulated Radiation Therapy
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Procedure: Therapeutic Conventional Surgery
- 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 ]The percentage of patients who experience toxicity at each dose level will be calculated, with a 95% confidence interval.
- Changes in MRI parameters [ Time Frame: Baseline to up to 4 years ]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 ]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.
- Pharmacokinetic (PK) parameters of gamma-secretase/Notch signalling pathway inhibitor RO4929097 [ Time Frame: Pre-dose, 30 minutes, 1, 2, 4, 6, and 8 hours ]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.
- 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 ]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).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01119599
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Virginia|
|University of Virginia Cancer Center|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Antonio Omuro||Memorial Sloan Kettering Cancer Center|