Clinical trial NCT03194906: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioma of Brain
Craniopharyngioma
Ependymoma
Germ Cell Tumor
Keywords: Pediatric oncology
Brain tumor
Low grade glioma
Cognitive late effects
Radiation therapy
Neuroprotection
Memantine
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-06-21
Enrollment: 34
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled trial design.
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Percent of approached participants who consent to study participation
timeFrame: Once, prior to enrollment
measure: Percent of participants who complete all 12 weeks of memantine/placebo therapy
timeFrame: At completion of memantine/placebo therapy (12 weeks)
measure: Percent of participants who complete at least 3 of 4 cognitive assessments
timeFrame: At end of study (up to one year after study enrollment)
Secondary outcomes:
measure: Change in neurobehavioral outcome
timeFrame: At baseline (prior to start of therapy) compared at end of radiation therapy (6 weeks later)
measure: Change in neurobehavioral outcome
timeFrame: At baseline (prior to start of therapy) compared at end of medication trial (12 weeks later)
measure: Change in neurobehavioral outcome
timeFrame: At baseline (prior to start of therapy) compared at follow-up (up to 1 year later)
measure: Frequency of memantine side effects
timeFrame: From start of memantine/placebo therapy through end of therapy (up to 12 weeks later)
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Heather M. Conklin, PhD
role: PRINCIPAL_INVESTIGATOR
References: