A Study to See if Memantine Protects the Brain During Radiation Therapy Treatment for Primary Central Nervous System Tumors

About

Brief Summary

This phase III trial compares memantine to placebo in treating patients with primary central nervous system tumors. 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 central nervous system tumors.

Primary Purpose

Supportive care

Study Type

Interventional

Phase

Phase 3

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

4 Years

Maximum Age

17 Years

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