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Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors

Primary Purpose

Glioma of Brain, Craniopharyngioma, Ependymoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Memantine

Placebo

Cognitive Assessment

About this trial

This is an interventional supportive care trial for Glioma of Brain focused on measuring Pediatric oncology, Brain tumor, Low grade glioma, Cognitive late effects, Radiation therapy, Neuroprotection, Memantine

Eligibility Criteria

6 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 6 years to 21 years at time of study enrollment
Diagnosis of localized low grade glioma [e.g., pilocytic astrocytoma, optic pathway glioma, ogligodendroglioma, ganglioglioma, pleomorphic xanthoastrocytoma (PXA)], craniopharyngioma, ependymoma, or germ cell tumor
Initiating focal cranial radiation therapy (photon or proton)
Laboratory tests [transaminases (ALT, AST, ALP), BUN and creatinine not greater than twice normal] and normal ECG
Speak, read and understand English sufficiently to complete study assessments
Adequate vision and hearing for valid completion of study measures
Negative βHCG pregnancy test among females of childbearing age
Participant must be able to swallow pills (psychology staff will be available to assist with pill swallowing training if needed)
Parent/Legal guardian available and able to speak, read and understand English

Exclusion Criteria:

Medical disorder that would endanger subject's well-being (e.g., uncorrected hypothyroidism, cardiac arrhythmia, hypertension requiring treatment, sick sinus syndrome, prolonged QTc)
History of significant neurological disease including poorly controlled seizures (i.e., > 1 seizure per month; anti-epileptic medications are acceptable), stroke, or head injury with loss of consciousness
Psychiatric condition that would preclude or take precedence over study participation (e.g., active psychosis, suicidal ideation)
IQ below 70 based on baseline/screening assessment
Treatment with psychotropic medication (psychostimulant, antidepressant, anxiolytic, antipsychotic) within the past two weeks, unless being prescribed specifically as an anti-emetic
History of substance abuse
History of hypersensitivity or reaction to NMDA receptor antagonists
History of prior cranial radiation therapy

Sites / Locations

St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Memantine

Placebo

Arm Description

Beginning at least two weeks prior to radiation therapy, participants receive memantine. Treatment continues for 12 weeks with periodic cognitive assessments and lab work.

Beginning at least two weeks prior to radiation therapy, participants receive a placebo. Treatment and assessment are identical to the memantine group.

Outcomes

Primary Outcome Measures

Percent of approached participants who consent to study participation

The rates of study participation and related 90% Blyth-Still-Casella intervals, as well as their regular 90% confidence interval, will be estimated. Test of one proportion will be performed against an estimated rate of 60%. The rate will be evaluated for the group as a whole as well as separately for the memantine intervention and placebo-control groups.

Percent of participants who complete all 12 weeks of memantine/placebo therapy

The rates of medication adherence and related 90% Blyth-Still-Casella intervals, as well as their regular 90% confidence interval, will be estimated. Test of one proportion will be performed against an estimated rate of 80%. The rate will be evaluated for the group as a whole as well as separately for the memantine intervention and placebo-control groups.

Percent of participants who complete at least 3 of 4 cognitive assessments

The rates of completion of cognitive assessments and related 90% Blyth-Still-Casella intervals, as well as their regular 90% confidence interval, will be estimated. Test of one proportion will be performed against an estimated rate of 75%. The rate will be evaluated for the group as a whole as well as separately for the memantine intervention and placebo-control groups.

Secondary Outcome Measures

Change in neurobehavioral outcome

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at 6 weeks (end of radiation therapy) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 6 weeks.

Change in neurobehavioral outcome

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at 12 weeks (end of medication trial) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 12 weeks.

Change in neurobehavioral outcome

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at follow-up (up to 1 year) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 1 year.

Frequency of memantine side effects

The frequency and nature of memantine side effects as measured by the SAFTEE will be evaluated qualitatively by calculating the frequency of side effect reporting by severity rating at different time points in the medication trial and comparing these frequencies across the memantine intervention and placebo-control groups. The frequency of side effects will be compared between the intervention and placebo-control groups using at t-test or other appropriate test, depending on the data distribution features of the compared outcome.

Full Information

NCT ID

NCT03194906

First Posted

June 19, 2017

Last Updated

July 12, 2023

Sponsor

St. Jude Children's Research Hospital

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03194906

Brief Title

Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors

Official Title

Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors: A Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

November 7, 2017 (Actual)

Primary Completion Date

June 28, 2023 (Actual)

Study Completion Date

June 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

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

Children with brain tumors who have had radiation therapy are at risk for problems with attention, memory, and problem solving. Such problems may cause difficulty in school and daily life. Memantine, the drug being used for this study, is not yet approved for use in children by the U.S. Food and Drug Administration. However, studies have shown some improvements in memory for patients with dementia, Attention Deficit Hyperactivity Disorder, and autism. Scientists have also used this medication for adult cancer patients receiving radiation therapy with results showing less cognitive declines over time compared to patients taking a placebo (inactive pill). These studies have also shown few side effects. This is a pilot/feasibility study and the first known study involving children with a cancer diagnosis or brain tumor. PRIMARY OBJECTIVES: To estimate the participation rate in a study of memantine used as a neuro-protective agent in children undergoing radiotherapy for localized brain tumors (low grade glioma, craniopharyngioma, ependymoma, or germ cell tumor) To estimate the rate of memantine medication adherence To estimate the rate of completion of cognitive assessments SECONDARY OBJECTIVES: To estimate the effect size of change in neurobehavioral outcomes (cognitive, social, quality of life, neurologic) associated with memantine To evaluate the frequency and nature of memantine side effects as measured by the Systematic Assessment for Treatment Emergent Events (SAFTEE)

Detailed Description

Participants will be randomized to take part in one of two groups: The Memantine Group will be prescribed memantine at a dosage following FDA-approved adult labeling. A low dose will initially be given beginning at least two weeks (± 7 days) prior to beginning radiation therapy. The dose will increase until participants reach the target dose of 20 mg/day. Memantine will be given for a total of 12 weeks. The Placebo Group will be prescribed identical capsules with no active drug. The placebo drug will be given in the same dose and frequency as described for the Memantine group. Participants will undergo the same evaluations and monitoring throughout the medication phase. Assessments will be done at baseline prior to study start, with follow-up assessments at 6 weeks (end of radiation therapy), and 12 weeks (end of study medication). Psychological testing to measure attention, working memory, problem solving, intelligence and academics will be done for each participant. Caregivers will also complete questionnaires about attention, problem solving, mood and interpersonal interactions. Caregivers will also be asked to complete a questionnaire about the family's general characteristics and medical history. At the time points noted above, blood work, vital signs and echocardiograms will be obtained, and the study neurologist will examine the participant to monitor side effects and neurological functioning. A study nurse will contact the participant once per week during the 12 weeks of medication administration to identify possible medication-related side effects and to check on rate of compliance with taking the medication. A remote app will be installed on the participant's home computer or cell phone to help remind them to take the medication and track success. At one year post medication, psychological and neurological examinations will be repeated.

6. Conditions and Keywords

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

Glioma of Brain, Craniopharyngioma, Ependymoma, Germ Cell Tumor

Keywords

Pediatric oncology, Brain tumor, Low grade glioma, Cognitive late effects, Radiation therapy, Neuroprotection, Memantine

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Randomized, double-blind, placebo-controlled trial design.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Memantine

Arm Type

Active Comparator

Arm Description

Beginning at least two weeks prior to radiation therapy, participants receive memantine. Treatment continues for 12 weeks with periodic cognitive assessments and lab work.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Beginning at least two weeks prior to radiation therapy, participants receive a placebo. Treatment and assessment are identical to the memantine group.

Intervention Type

Drug

Intervention Name(s)

Memantine

Other Intervention Name(s)

Memantine hydrochloride, Namenda®

Intervention Description

Medication dosing will be overseen by one of the study neurologists, with step-wise dose reductions (5 mg intervals) allowable in the case of side effects.

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

Look-alike drug

Intervention Description

A placebo that appears exactly like the study drug, memantine, will be given in a manner identical to the study drug.

Intervention Type

Other

Intervention Name(s)

Cognitive Assessment

Other Intervention Name(s)

Cognitive and neurologic examinations

Intervention Description

Cognitive and neurologic examinations will be conducted to assess cognitive, social, quality of life, and neurological outcomes associated with memantine will be completed at baseline prior to medication start, and at 6 weeks (end of radiation therapy), 12 weeks (discontinuation of study medication or placebo), and one year post radiation therapy.

Primary Outcome Measure Information:

Title

Percent of approached participants who consent to study participation

Description

Time Frame

Once, prior to enrollment

Title

Percent of participants who complete all 12 weeks of memantine/placebo therapy

Description

Time Frame

At completion of memantine/placebo therapy (12 weeks)

Title

Percent of participants who complete at least 3 of 4 cognitive assessments

Description

Time Frame

At end of study (up to one year after study enrollment)

Secondary Outcome Measure Information:

Title

Change in neurobehavioral outcome

Description

Time Frame

At baseline (prior to start of therapy) compared at end of radiation therapy (6 weeks later)

Title

Change in neurobehavioral outcome

Description

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at 12 weeks (end of medication trial) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 12 weeks.

Time Frame

At baseline (prior to start of therapy) compared at end of medication trial (12 weeks later)

Title

Change in neurobehavioral outcome

Description

The effect size (Cohen's d- the standardized difference between two means) of memantine on neurobehavioral outcomes (cognitive, social, quality of life, neurologic) will be estimated by comparing performance at baseline to performance at follow-up (up to 1 year) using paired difference divided by its estimated standard deviation. In addition, due to the missing data, mixed-effects models will be fitted to investigate the change of outcome from baseline to 1 year.

Time Frame

At baseline (prior to start of therapy) compared at follow-up (up to 1 year later)

Title

Frequency of memantine side effects

Description

Time Frame

From start of memantine/placebo therapy through end of therapy (up to 12 weeks later)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 6 years to 21 years at time of study enrollment Diagnosis of localized low grade glioma [e.g., pilocytic astrocytoma, optic pathway glioma, ogligodendroglioma, ganglioglioma, pleomorphic xanthoastrocytoma (PXA)], craniopharyngioma, ependymoma, or germ cell tumor Initiating focal cranial radiation therapy (photon or proton) Laboratory tests [transaminases (ALT, AST, ALP), BUN and creatinine not greater than twice normal] and normal ECG Speak, read and understand English sufficiently to complete study assessments Adequate vision and hearing for valid completion of study measures Negative βHCG pregnancy test among females of childbearing age Participant must be able to swallow pills (psychology staff will be available to assist with pill swallowing training if needed) Parent/Legal guardian available and able to speak, read and understand English Exclusion Criteria: Medical disorder that would endanger subject's well-being (e.g., uncorrected hypothyroidism, cardiac arrhythmia, hypertension requiring treatment, sick sinus syndrome, prolonged QTc) History of significant neurological disease including poorly controlled seizures (i.e., > 1 seizure per month; anti-epileptic medications are acceptable), stroke, or head injury with loss of consciousness Psychiatric condition that would preclude or take precedence over study participation (e.g., active psychosis, suicidal ideation) IQ below 70 based on baseline/screening assessment Treatment with psychotropic medication (psychostimulant, antidepressant, anxiolytic, antipsychotic) within the past two weeks, unless being prescribed specifically as an anti-emetic History of substance abuse History of hypersensitivity or reaction to NMDA receptor antagonists History of prior cranial radiation therapy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Heather M. Conklin, PhD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

Clinical Trials Open at St. Jude

Learn more about this trial

Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors

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