This phase I trial is studying the side effects and best dose of vandetanib when given together with radiation therapy in treating young patients with newly diagnosed diffuse brain stem glioma.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
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.
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
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
To determine the toxicities associated with the chronic use of vandetanib in pediatric patients
Time frame: 3 Years
To characterize the pharmacokinetics of vandetanib in pediatric patients
Time frame: 3 Years
To evaluate the influence of specific polymorphisms on the pharmacokinetics of vandetanib in children
Time frame: 3 Years
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
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
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
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