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

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

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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Percent of approached participants who consent to study participation

Secondary Outcome

 Change in neurobehavioral outcome

Condition

Glioma of Brain

Intervention

Memantine

Study Arms / Comparison Groups

 Memantine

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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

50

Start Date

November 7, 2017

Completion Date

March 2023

Primary Completion Date

March 2022

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
      

Gender

All

Ages

6 Years - 21 Years

Accepts Healthy Volunteers

No

Contacts

Heather M. Conklin, PhD, 866-278-5833, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT03194906

Organization ID

MEMCRT

Secondary IDs

R21CA218625

Responsible Party

Sponsor

Study Sponsor

St. Jude Children's Research Hospital

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Heather M. Conklin, PhD, Principal Investigator, St. Jude Children's Research Hospital

Verification Date

April 2021