A Study to See if Memantine Protects the Brain During Radiation Therapy Treatment for a Brain Tumor

Inclusion Criteria:

• >= 4 and < 18 years at time of study entry

• Patients must weigh 15 kg or greater at time of study entry

• Primary central nervous system tumors that have not received prior cranialradiotherapy

• Planned focal, cranial or craniospinal radiation treatment for a primary centralnervous system tumor

• The patient must have receptive and expressive language skills in English, French orSpanish since the neurocognitive function and quality of life (QOL) assessmentinstruments are available in these languages only

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:

• Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female

• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female

• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female

• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female

• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135U/L

• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to thevalue of 45 U/L

• The patient must be able to undergo magnetic resonance imaging

• All patients and/or their parents or legal guardians must sign a written informedconsent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Life expectancy of less than 18 months

• Pre-existing conditions:

• Any contraindication or allergy to study drug (memantine or placebo)

• Intractable seizures while on adequate anticonvulsant therapy, defined as morethan one seizure per month for the past 2 months or since initiatinganticonvulsant therapy

• History of neurodevelopmental disorder such as Down syndrome, Fragile X,William's Syndrome, intellectual disability (presumed intelligence quotient [IQ] < 70), etc

• Co-morbid systemic illnesses, psychiatric conditions, social situations, orother severe concurrent disease which, in the judgment of the investigator,would make the patient inappropriate for entry into this study or interferesignificantly with the proper assessment of safety and toxicity of theprescribed regimens or would limit compliance with the study requirements

• Patients with a motor, visual, or auditory condition that precludesparticipation in computerized neurocognitive assessments

• Patients with any medical condition or taking medications that lead toalterations of urine pH towards the alkaline condition (e.g., renal tubularacidosis, carbonic anhydrase inhibitors, sodium bicarbonate)

• Personal history of prior cranial or craniospinal radiotherapy is not allowed

• Note: Prior anti-cancer therapy including surgery, chemotherapy, targetedagents are allowed as per standard of care clinical treatment guidelines

• Female patients who are pregnant are excluded since fetal toxicities and teratogeniceffects have been noted for the study drug. A pregnancy test is required for femalepatients of childbearing potential

• Lactating females who plan to breastfeed their infants

• Sexually active patients of reproductive potential who do not agree to use aneffective contraceptive method for the duration of their study participation