A Phase 3 Randomized, Placebo-Controlled Trial Evaluating Memantine for Neurocognitive Protection in Children Undergoing Cranial Radiotherapy as Part of Treatment for Primary Central Nervous System Tumors.

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 cranial

radiotherapy

- Planned focal, cranial or craniospinal radiation treatment for a primary central

nervous system tumor

- The patient must have receptive and expressive language skills in English, French or

Spanish since the neurocognitive function and quality of life (QOL) assessment

instruments are available in these languages only

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70

mL/min/1.73 m^2 or a serum creatinine based on age/gender 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]) =< 135

U/L

- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the

value 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 informed

consent

- 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 more

than one seizure per month for the past 2 months or since initiating

anticonvulsant 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, or other

severe concurrent disease which, in the judgment of the investigator, would make

the patient inappropriate for entry into this study or interfere significantly

with the proper assessment of safety and toxicity of the prescribed regimens or

would limit compliance with the study requirements

- Patients with a motor, visual, or auditory condition that precludes participation

in computerized neurocognitive assessments

- Patients with any medical condition or taking medications that lead to

alterations of urine pH towards the alkaline condition (e.g., renal tubular

acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)

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

- Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents

are allowed as per standard of care clinical treatment guidelines

- Female patients who are pregnant are excluded since fetal toxicities and teratogenic

effects have been noted for the study drug. A pregnancy test is required for female

patients of childbearing potential

- Lactating females who plan to breastfeed their infants

- Sexually active patients of reproductive potential who do not agree to use an

effective contraceptive method for the duration of their study participation