Phase I Trial of Vandetanib (ZD6474, ZACTIMA) With Concurrent Radiation in Treatment of Newly Diagnosed Brainstem Glioma
Phase I Trial of Vandetanib (ZD6474, ZACTIMA) With Concurrent Radiation in Treatment of Newly Diagnosed Brainstem Glioma
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.
Diagnosis of 1 of the following:
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