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

NCT03194906 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: MEMCRTR21CA218625NCI-2017-01279
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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)

Conditions

Glioma of Brain; Craniopharyngioma; Ependymoma; Germ Cell Tumor

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  Once, prior to enrollment

• 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.

  At completion of memantine/placebo therapy (12 weeks)

• 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.

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

Secondary Outcomes (4)

• Change in neurobehavioral outcome

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

• Change in neurobehavioral outcome

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

• Change in neurobehavioral outcome

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

• Frequency of memantine side effects

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

Study Arms (2)

Memantine

ACTIVE COMPARATOR

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

Drug: Memantine; Other: Cognitive Assessment

Placebo

PLACEBO COMPARATOR

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

Other: Placebo; Other: Cognitive Assessment

Interventions

Memantine DRUG

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.

Also known as: Memantine hydrochloride, Namenda®

Memantine

Placebo OTHER

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

Also known as: Look-alike drug

Placebo

Cognitive Assessment OTHER

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.

Also known as: Cognitive and neurologic examinations

Memantine; Placebo

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Craniopharyngioma; Ependymoma; Neoplasms, Germ Cell and Embryonal; Brain Neoplasms

Interventions

Memantine; Medication Errors; Mental Status and Dementia Tests

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Drug Therapy; Therapeutics; Medical Errors; Health Services; Health Care Facilities Workforce and Services; Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Heather M. Conklin, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled trial design.

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 21, 2017
• Study Start: November 7, 2017
• Primary Completion: June 28, 2023
• Study Completion: June 28, 2023
• Last Updated: July 13, 2023

Record last verified: 2023-07

Locations

US (1)