- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04217694
Memantine for the Reduction of Cognitive Impairment After Radiation Therapy in Pediatric Patients With Central Nervous System Tumors
A Pilot Study Evaluating the Feasibility of Memantine in Reducing Cognitive Impairment in Pediatric Patients After Radiation Therapy for Central Nervous System Tumors
Study Overview
Status
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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
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:
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.
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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.
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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.
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Baseline up to 12 months post-RT
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Change in NCF
Time Frame: Baseline up to 6 months post-RT
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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.
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Baseline up to 6 months post-RT
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Change in NCF
Time Frame: Baseline up to 6 months post-RT
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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
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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.
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Baseline up to 12 months post-RT
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Disease-freedom from primary tumor
Time Frame: Up to 2 years
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Will be analyzed using Kaplan-Meier.
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Up to 2 years
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Overall survival
Time Frame: Up to 2 years
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Will be analyzed using Kaplan-Meier.
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Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Nadia N. Laack, M.D., Mayo Clinic
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Neoplasms by Site
- Neurocognitive Disorders
- Cognition Disorders
- Neoplasms
- Cognitive Dysfunction
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Dopamine Agents
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Memantine
Other Study ID Numbers
- MC1911 (Other Identifier: Mayo Clinic)
- NCI-2019-08538 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 19-004245 (Other Identifier: Mayo Clinic Institutional Review Board)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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