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

Primary Purpose

Malignant Central Nervous System Neoplasm, Primary Central Nervous System Neoplasm

Status

Active

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cogstate Assessment Battery

Memantine

Memantine Hydrochloride

About this trial

This is an interventional supportive care trial for Malignant Central Nervous System Neoplasm

Eligibility Criteria

4 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prevention (memantine, CogState)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT04217694

First Posted

December 23, 2019

Last Updated

July 20, 2023

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04217694

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 17, 2020 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Central Nervous System Neoplasm, Primary Central Nervous System Neoplasm

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Prevention (memantine, CogState)

Arm Type

Experimental

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Cogstate Assessment Battery

Intervention Description

Complete CogState testing

Intervention Type

Drug

Intervention Name(s)

Memantine

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

Memantine Hydrochloride

Other Intervention Name(s)

Ebixia, Namenda

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Percentage of patients who attempt to take appropriate dose of memantine

Description

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.

Time Frame

At 1 month post-radiation therapy (RT)

Secondary Outcome Measure Information:

Title

Percentage of patients who attempt to take appropriate dose of memantine

Description

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.

Time Frame

At 3 and 6 months post-RT

Other Pre-specified Outcome Measures:

Title

Change in neurocognitive function (NCF)

Description

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.

Time Frame

Baseline up to 12 months post-RT

Title

Change in NCF

Description

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.

Time Frame

Baseline up to 6 months post-RT

Title

Change in NCF

Description

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.

Time Frame

Baseline up to 6 months post-RT

Title

Change in quantitative volumetric brain imaging

Description

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.

Time Frame

Baseline up to 12 months post-RT

Title

Change in cognition

Description

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.

Time Frame

Baseline up to 12 months post-RT

Title

Disease-freedom from primary tumor

Description

Will be analyzed using Kaplan-Meier.

Time Frame

Up to 2 years

Title

Overall survival

Description

Will be analyzed using Kaplan-Meier.

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nadia N Laack

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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