Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
Condition: Glioma of Brain; Craniopharyngioma; Ependymoma; Germ Cell Tumor
MeSH terms: Brain Neoplasms; Neoplasms, Germ Cell and Embryonal; Ependymoma; Craniopharyngioma; Adamantinoma
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Memantine; Placebo; Cognitive Assessment
Intervention type(s): Drug; Other; Other
Intervention description(s): 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.; A placebo that appears exactly like the study drug, memantine, will be given in a manner identical to the study drug.; 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.
Other intervention name(s): Memantine hydrochloride; Namenda®; Look-alike drug; Cognitive and neurologic examinations
Intervention MeSH terms: Memantine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind, placebo-controlled trial design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Pediatric oncology; Brain tumor; Low grade glioma; Cognitive late effects; Radiation therapy; Neuroprotection; Memantine