Brain and Central Nervous System Tumors
Conditions
Keywords
untreated childhood brain stem glioma
Brief summary
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.
Detailed description
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.
Interventions
DRUGvandetanib
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.
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of 1 of the following: * Diffuse brainstem glioma * High-grade glioma originating from brainstem * Age must be greater than or equal to 2 years and less than 21 years * Newly diagnosed disease * Lansky OR Karnofsky performance status 40-100% * ANC ≥ 1,000/mm³ * Platelet count ≥ 100,000/mm³ (transfusion independent) * Hemoglobin ≥ 8 g/dL (transfusion allowed) * Bilirubin \< 1.5 times upper limit of normal (ULN) for age * ALT \< 5 times ULN * Albumin ≥ 2 g/dL * Creatinine \< 2 times ULN for age OR glomerular filtration rate \> 70 mL/min * QTc interval \< 450 msec by EKG * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | 3 Years |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the influence of specific polymorphisms on the pharmacokinetics of vandetanib in children | 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 | 3 Years |
| To characterize the pharmacokinetics of vandetanib in pediatric patients | 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 | 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 | 3 Years |
| To determine the toxicities associated with the chronic use of vandetanib in pediatric patients | 3 Years |
Countries
United States
Outcome results
None listed