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

November 29, 2023 updated by: Mayo Clinic

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

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.

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prevention (memantine, CogState)
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.
Given PO
Other Names:
  • Namenda
  • Ebixia
Complete CogState testing
Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients who attempt to take appropriate dose of memantine
Time Frame: At 1 month post-radiation therapy (RT)
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
Time Frame: At 3 and 6 months post-RT
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in neurocognitive function (NCF)
Time Frame: Baseline up to 12 months post-RT
Will be summarized and reported descriptively. This will be assessed using results from neurocognitive testing. Differences between scores from baseline and 12 months post-RT will be calculated, along with corresponding 90% confidence intervals. Change index (reliable change index [RCI]) will be calculated as well over this time period. A paired t-test or the Wilcoxon rank-sum test will be used as applicable. Additional analyses concerning change in NCF using additional subscales from the results of neurocognitive testing may be performed, but will be hypothesis generating and considered exploratory. These may include the use of other neurocognitive testing subscales using t-tests or the Wilcoxon rank-sum test, variations of RCI, and linear regression to assess the relationship of each subscale with changes in NCF.
Baseline up to 12 months post-RT
Change in NCF
Time Frame: Baseline up to 6 months post-RT
Determined by the CogState composite score. Will be summarized and compared to baseline values. A paired t-test or the Wilcoxon rank-sum test will be used as applicable. Additional analyses concerning NCF at or between various time points may be performed, but will be hypothesis generating and considered exploratory. These may include comparisons of NCF between baseline and the end of RT, 3 months, and 12 months post-RT using a t-test or Wilcoxon rank-sum test, as well as creation of a linear mixed model to longitudinally assess changes over time. Subscales of the results from the CogState may also be used for these analyses.
Baseline up to 6 months post-RT
Change in NCF
Time Frame: Baseline up to 6 months post-RT
Determined by neuropsychological examination. Will be summarized and compared to baseline values. A paired t-test or the Wilcoxon rank-sum test will be used as applicable. Additional analyses concerning change in NCF at or between various time points may be performed, but will be hypothesis generating and considered exploratory. These may include comparisons of NCF between baseline and the end of RT, 3 months, and 12 months post-RT using a t-test or Wilcoxon rank-sum test, as well as creation of a linear mixed model to longitudinally assess changes over time.
Baseline up to 6 months post-RT
Change in quantitative volumetric brain imaging
Time Frame: Baseline up to 12 months post-RT
Neuroquant Software will be used to analyze quantitative magnetic resonance imaging measurements of changes in hippocampal volume. Differences between measurements will be reported, along with corresponding 90% confidence intervals. A paired t-test or the Wilcoxon rank-sum test will be used as applicable. Additional analyses concerning hippocampal volume may be performed, but will be hypothesis generating and considered exploratory.
Baseline up to 12 months post-RT
Change in cognition
Time Frame: Baseline up to 12 months post-RT
Cognitive changes detected by the CogState composite score will be correlated with results from formal neuropsychological testing using Pearson's r or Spearman's rank method, as applicable.
Baseline up to 12 months post-RT
Disease-freedom from primary tumor
Time Frame: Up to 2 years
Will be analyzed using Kaplan-Meier.
Up to 2 years
Overall survival
Time Frame: Up to 2 years
Will be analyzed using Kaplan-Meier.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Nadia N. Laack, M.D., Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 17, 2020

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

December 23, 2019

First Submitted That Met QC Criteria

January 2, 2020

First Posted (Actual)

January 3, 2020

Study Record Updates

Last Update Posted (Estimated)

December 5, 2023

Last Update Submitted That Met QC Criteria

November 29, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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