Memantine for the Reduction of Cognitive Impairment After Radiation Therapy in Pediatric Patients With Central Nervous System Tumors

Study Overview
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Brief Summary
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This early phase I trial studies the feasibility of giving memantine for the reduction of cognitive impairment after radiation therapy in pediatric patients with central nervous system tumors. Memantine may reduce the effects of radiation therapy on memory and thinking.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the feasibility of twice daily memantine started before radiation therapy (RT) and one month after RT. SECONDARY OBJECTIVE: I. To evaluate the feasibility of twice daily (BID) memantine started before RT and continued 3 and 6 months after RT. EXPLORATORY OBJECTIVES: I. To evaluate the change in neurocognitive function (NCF) as found by formal neurocognitive testing between baseline and 12 months post-RT. II. To compare the change in NCF between baseline and the end of RT, 3,and 6 months after RT using both neuropsychological testing and the CogState exam. III. To evaluate changes in quantitative volumetric brain imaging using Neuroquant software analysis of magnetic resonance imaging (MRI) imaging before and 12 months after radiation. IV. To correlate cognitive changes detected by CogState composite score and formal neuropsychological testing. V. Disease-free (of primary tumor) and overall survival. OUTLINE: Patients receive memantine orally (PO) BID beginning at the time of study enrollment (no later than 1st day of RT) up to 6 months after completion of standard of care RT in the absence of unacceptable toxicity. Patients also complete CogState cognitive testing at baseline, at completion of RT, and at 3, 6, and 12 months after completion of RT. After completion of study, patients are followed up periodically.

Official Title
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A Pilot Study Evaluating the Feasibility of Memantine in Reducing Cognitive Impairment in Pediatric Patients After Radiation Therapy for Central Nervous System Tumors

Conditions
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Malignant Central Nervous System Neoplasm, Primary Central Nervous System Neoplasm

Intervention / Treatment
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* Behavioral: Cogstate Assessment Battery
* Drug: Memantine
* Drug: Memantine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Receiving intracranial radiation for a primary central nervous system (CNS) malignancy Histological or radiologic confirmation of intracranial disease Able to use the computer for CogState assessment battery Normal serum creatinine per institutional normal limits (obtained =< 35 days prior to study entry) Total bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN (obtained =< 35 days prior to study entry) Aspartate transaminase (AST) AND alanine transaminase (ALT) =< 2.5 x ULN Provide informed consent if over age 18, or provide assent with consent from parent or legal guardian if age 7-17 Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only. Patients capable of childbearing must use adequate contraception Exclusion Criteria: Patients with World Health Organization (WHO) grade IV astrocytoma or glioblastoma tumors Note: A patient with grade IV tumors of other histology can participate in the study if they meet all other criteria Any prior intracranial radiation Any contraindication or allergy to memantine Use of short-acting benzodiazepines (may excite lethargy/dizziness with memantine) Note: occasional use as a sleep aid or as needed for anxiety or nausea is allowed Intractable seizures while on adequate anticonvulsant therapy, defined as more than one seizure per month for the past 2 months Co-morbid systemic illnesses 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 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention (memantine, CogState)<br>Patients receive memantine PO BID beginning at the time of study enrollment (no later than 1st day of RT) up to 6 months after completion of standard of care RT in the absence of unacceptable toxicity. Patients also complete CogState cognitive testing at baseline, at completion of RT, and at 3, 6, and 12 months after completion of RT. | Behavioral: Cogstate Assessment Battery<br>* Complete CogState testing<br>Drug: Memantine<br>* Given PO<br>Drug: Memantine Hydrochloride<br>* Given PO<br>* Other names: Namenda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who attempt to take appropriate dose of memantine | The rate of feasibility (the percentage of patients who attempt to take at least 80% percent of their prescribed dose) will be calculated, along with corresponding 90% confidence intervals. | At 1 month post-radiation therapy (RT) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who attempt to take appropriate dose of memantine | The rate of feasibility (the percentage of patients who attempt to take at least 80% percent of their prescribed dose) will be calculated, along with corresponding 90% confidence intervals. | At 3 and 6 months post-RT |