This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Children with newly diagnosed intrinsic brain stem gliomas (BSG) and incompletely resected supratentorial malignant gliomas (STMG) with residual tumor on imaging will be eligible for this study. The study will consist of an initial dose finding (phase I) component, and a subsequent efficacy (phase II) component for patients with brain stem gliomas. For the purpose of dose finding, two strata will be identified. 1) BSG and STMG not receiving enzyme inducing anticonvulsant drugs (EIACD) and 2) STMG receiving anticonvulsants. In each stratum, the beginning dose of ZD1839 will be 100 mg/m2/day commencing with the beginning of radiation therapy. In the absence of disease progression or dose-limiting toxicity, treatment will continue for one year. Treatment may continue longer if drug is benefiting the patients and continues to be available. Daily doses of ZD1839 to be studied subsequently are 250 mg/m2, 375 mg/m2, 500 mg/m2, 650 mg/m2 and 850 mg/m 2. De-escalation of the starting dose to 75 mg/m2 will be permitted, in the event of a dose limiting toxicity at the first dose level. The dose-limiting toxicity observation period for the purpose of establishing safety during radiotherapy will conclude two weeks following completion of radiation therapy. Pharmacokinetics will be evaluated for each patient and if the blood levels obtained at 850 mg/m2/day are substantially less than obtained in adults at the adult MTD further dose levels may be studied unless a MTD has been reached. When the MTD is determined or the highest dose level reached (whichever is lowest), efficacy will be investigated further only in patients with BSG by enrolling additional patients at that dose for Stratum 1. The efficacy endpoint will be progression-free survival.
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