Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors

Children with brain tumors who have had radiation therapy are at risk for problems with attention, memory, and problem solving. Such problems may cause difficulty in school and daily life. Memantine, the drug being used for this study, is not yet approved for use in children by the U.S. Food and Drug Administration. However, studies have shown some improvements in memory for patients with dementia, Attention Deficit Hyperactivity Disorder, and autism. Scientists have also used this medication for adult cancer patients receiving radiation therapy with results showing less cognitive declines over time compared to patients taking a placebo (inactive pill). These studies have also shown few side effects. This is a pilot/feasibility study and the first known study involving children with a cancer diagnosis or brain tumor. PRIMARY OBJECTIVES: * To estimate the participation rate in a study of memantine used as a neuro-protective agent in children undergoing radiotherapy for localized brain tumors (low grade glioma, craniopharyngioma, ependymoma, or germ cell tumor) * To estimate the rate of memantine medication adherence * To estimate the rate of completion of cognitive assessments SECONDARY OBJECTIVES: * To estimate the effect size of change in neurobehavioral outcomes (cognitive, social, quality of life, neurologic) associated with memantine * To evaluate the frequency and nature of memantine side effects as measured by the Systematic Assessment for Treatment Emergent Events (SAFTEE)

Inclusion Criteria: * Age 6 years to 21 years at time of study enrollment * Diagnosis of localized low grade glioma \[e.g., pilocytic astrocytoma, optic pathway glioma, ogligodendroglioma, ganglioglioma, pleomorphic xanthoastrocytoma (PXA)\], craniopharyngioma, ependymoma, or germ cell tumor * Initiating focal cranial radiation therapy (photon or proton) * Laboratory tests \[transaminases (ALT, AST, ALP), BUN and creatinine not greater than twice normal\] and normal ECG * Speak, read and understand English sufficiently to complete study assessments * Adequate vision and hearing for valid completion of study measures * Negative βHCG pregnancy test among females of childbearing age * Participant must be able to swallow pills (psychology staff will be available to assist with pill swallowing training if needed) * Parent/Legal guardian available and able to speak, read and understand English Exclusion Criteria: * Medical disorder that would endanger subject's well-being (e.g., uncorrected hypothyroidism, cardiac arrhythmia, hypertension requiring treatment, sick sinus syndrome, prolonged QTc) * History of significant neurological disease including poorly controlled seizures (i.e., \> 1 seizure per month; anti-epileptic medications are acceptable), stroke, or head injury with loss of consciousness * Psychiatric condition that would preclude or take precedence over study participation (e.g., active psychosis, suicidal ideation) * IQ below 70 based on baseline/screening assessment * Treatment with psychotropic medication (psychostimulant, antidepressant, anxiolytic, antipsychotic) within the past two weeks, unless being prescribed specifically as an anti-emetic * History of substance abuse * History of hypersensitivity or reaction to NMDA receptor antagonists * History of prior cranial radiation therapy