Vandetanib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Diffuse Brainstem Glioma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Vandetanib (ZD6474, ZACTIMA) With Concurrent Radiation in Treatment of Newly Diagnosed Brainstem Glioma|
- To estimate the maximum tolerated dose (MTD) and to determine the dose-limiting toxicity (DLT) of vandetanib administered concurrently with radiation therapy (RT) in pediatric patients with newly diagnosed diffuse brainstem glioma. [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]
- To determine the toxicities associated with the chronic use of vandetanib in pediatric patients [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]
- To characterize the pharmacokinetics of vandetanib in pediatric patients [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
- To evaluate the influence of specific polymorphisms on the pharmacokinetics of vandetanib in children [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
- To prospectively investigate the role of innovative imaging techniques (e.g., perfusion/diffusion, susceptibility-weighted imaging, arterial spin labeling) in assessing the response to therapy, particularly in tumor vascularization and perfusion [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
- To prospectively estimate the cumulative incidence of intratumoral hemorrhage in patients with diffuse brainstem glioma treated with vandetanib concurrently with and after RT in the context of a Phase I study [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
- Prospectively assess the number of circulating endothelial cells and circulating endothelial progenitors before the start and during therapy and, if possible, to correlate these findings with tumor response, imaging studies, and other biological assays [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
|Study Start Date:||April 2007|
|Study Completion Date:||October 2011|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Experimental: Pediatric Diffuse Brainstem Glioma Patients
Patients with newly diagnosed diffuse brainstem gliomas receive vandetanib.
Oral vandetanib administration will start on the same day as RT. Treatment with vandetanib will extend for the entire duration of RT, and then will be continued after completion of RT for a maximum duration of 2 years.
Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving vandetanib together with radiation therapy may kill more tumor cells.
Patients undergo conformal radiotherapy once daily, 5 days a week, for 6 weeks. Patients also receive oral vandetanib once daily beginning on the same day as radiotherapy and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of vandetanib until the maximum tolerated dose (MTD) is determined.
Blood samples are collected periodically for pharmacokinetic studies, polymorphism analysis (e.g., CYP3A4/5), and immunological laboratory methods (e.g., western blot assay). Imaging studies are also conducted periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00472017
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Principal Investigator:||Alberto Broniscer, MD||St. Jude Children's Research Hospital|