Vandetanib and Radiation Therapy in Treating Young Patients With Newly Diagnosed Diffuse Brainstem 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.

• 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