Cediranib, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma
This phase I/II trial is studying the side effects and best dose of cediranib to see how well it works when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cediranib together with temozolomide and radiation therapy may kill more tumor cells.
Adult Giant Cell Glioblastoma
Drug: Cediranib Maleate
Radiation: Intensity-Modulated Radiation Therapy
Radiation: Fludeoxyglucose F-18
Procedure: Perfusion Magnetic Resonance Imaging
Procedure: Diffusion Tensor Imaging
Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Procedure: Diffusion Weighted Imaging
Procedure: Positron Emission Tomography
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase Ib/II Study of AZD2171 in Combination With Daily Temozolomide and Radiation in Patients With Newly Diagnosed Glioblastoma Not Taking Enzyme-Inducing Anti-epileptic Drugs|
- Safety profile and optimal dose of cediranib during chemoradiotherapy (Phase I) [ Time Frame: Up to 30 days after the last dose ] [ Designated as safety issue: Yes ]A dose-limiting toxicity of cediranib is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications/temozolomide and occurs following the first dose of cediranib in the chemoradiation.
- Progression-free survival (Phase II) [ Time Frame: At day 218 ] [ Designated as safety issue: No ]The fraction of patients alive and free of disease progression after the MRI scan scheduled. This fraction will be compared, using a one sample, two-sided exact binomial test, to 50% progression-free survival (PFS). For safety assessment, the study will be powered to ensure at least 85% chance of observing a serious adverse event, if the probability of such an event on treatment were >=5%.
- MRI parameters (Phase II) [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]The comparisons of all MRI measurements will be against their day -1 values (baseline), using a 2-sided, paired Wilcoxon test (Hollander and Wolfe 1973).
- Blood biomarkers (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Log-transformation is expected to yield approximately homogenous and symmetric standard errors, both for Poisson events and quantities obtained by assays with successive dilutions. We will plot the median levels and quartiles over time. First, we will compare on-study values to baseline, than we will test for an association between treatment time and markers, using a linear mixed effects model with log-transformed data and a spline function of time. The two-sided, paired t-test test will be powered to detect an effect-size of 0.5.
- Tumor biomarkers (Phase II) [ Time Frame: At baseline ] [ Designated as safety issue: No ]Exploratory analyses will be performed to determine if there is any correlation between the molecular/vascular phenotype of the tumor or quantitative measurements, we will use for this purpose ANOVA on log-transformed marker measurements. We will analyze changes in the measurements, and correlate biomarkers with clinical and radiographic response, similarly as for blood and urine biomarkers.
|Study Start Date:||April 2008|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor therapy, chemotherapy, IMRT)
See Detailed Description
Drug: Cediranib Maleate
Other Names:Drug: Temozolomide
Other Name: TMZRadiation: Intensity-Modulated Radiation Therapy
Other Names:Radiation: Fludeoxyglucose F-18
Undergo 18 FDG PET
Other Name: 18FDGProcedure: Perfusion Magnetic Resonance Imaging
Other Name: PW-MRIProcedure: Diffusion Tensor Imaging
Other Name: DTIProcedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Other Names:Procedure: Diffusion Weighted Imaging
Undergo T1 weighted DCE-MRI
Other Names:Procedure: Positron Emission Tomography
Undergo 18 F FDG-PET
Other Names:Other: Laboratory Biomarker Analysis
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00662506
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Tracy Batchelor||Massachusetts General Hospital|