PRIMARY OBJECTIVE:~I. To determine the efficacy, as measured by the slope of change of the Cogstate composite Z score from baseline to 12 months, of oral memantine hydrochloride (memantine) administered for a period of 6 months, when compared to placebo, in children ages 4-18 receiving cranial or craniospinal radiotherapy for primary central nervous system tumors.~EXPLORATORY OBJECTIVES:~I. To determine if memantine is associated with improved cognitive function as measured for participants in the optional Children's Oncology Group (COG) Standardized Battery at 12 months.~II. To determine if memantine is associated with change in cognitive function version (vs.) placebo as measured by Cogstate composite score at end of radiation therapy (RT), 3 and 6 months.~III. To determine if memantine is associated with differences in cognitive function vs. placebo as measured by Cogstate composite score at 30 and 60 months for participants in the optional COG Standardized Battery.~IV. To correlate early cognitive changes (end of RT, 3, 6, 12 months Cogstate composite score) with late cognitive function (30 and 60 months Cogstate composite score).~V. To correlate COG Standardized Battery scores to Cogstate composite scores at 12, 30, and 60 months.~VI. To estimate the 36-month disease-free and overall survival (of primary brain tumor) after memantine treatment compared to placebo.~VII. To correlate changes in quantitative volumetric magnetic resonance imaging (MRI) measurements of critical brain regions with cognitive function over time.~VIII. To evaluate impact of memantine versus placebo on molecular biomarkers associated with cognitive decline after radiotherapy.~IX. To determine whether oral memantine, when compared to placebo, is associated with reduction in the incidence of decline of composite Cogstate score at 12 months in children ages 4-18 receiving cranial radiotherapy for primary central nervous system tumors.~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM I: Patients receive memantine hydrochloride orally (PO) twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also complete cognitive testing over 20-30 minutes at baseline, end of radiation therapy, and at 3, 6, 12, 30, and 60 months.~ARM II: Patients receive placebo PO BID for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also complete cognitive testing over 20-30 minutes at baseline, end of radiation therapy, and at 3, 6, 12, 30, and 60 months.
This phase III trial compares memantine to usual treatment in treating patients with brain tumors that are newly diagnosed or have come back (recurrent). Memantine may block receptors (parts of nerve cells) in the brain known to contribute to a decline in cognitive function. Giving memantine may make a difference in cognitive function (attention, memory, or other thought processes) in children and adolescents receiving brain radiation therapy to treat a primary brain tumor.