Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03194906
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : April 18, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

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)

Condition or disease Intervention/treatment Phase
Glioma of Brain Craniopharyngioma Ependymoma Germ Cell Tumor Drug: Memantine Other: Placebo Other: Cognitive Assessment Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
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
Official Title: Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors: A Pilot Study
Actual Study Start Date : November 7, 2017
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021


Arm Intervention/treatment
Active Comparator: Memantine
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
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.
Other Names:
  • Memantine hydrochloride
  • Namenda®

Other: Cognitive Assessment
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 Name: Cognitive and neurologic examinations

Placebo Comparator: Placebo
Beginning at least two weeks prior to radiation therapy, participants receive a placebo. Treatment and assessment are identical to the memantine group.
Other: Placebo
A placebo that appears exactly like the study drug, memantine, will be given in a manner identical to the study drug.
Other Name: Look-alike drug

Other: Cognitive Assessment
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 Name: Cognitive and neurologic examinations




Primary Outcome Measures :
  1. Percent of approached participants who consent to study participation [ Time Frame: Once, prior to enrollment ]
    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.

  2. Percent of participants who complete all 12 weeks of memantine/placebo therapy [ Time Frame: At completion of memantine/placebo therapy (12 weeks) ]
    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.

  3. Percent of participants who complete at least 3 of 4 cognitive assessments [ Time Frame: At end of study (up to one year after study enrollment) ]
    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 :
  1. Change in neurobehavioral outcome [ Time Frame: At baseline (prior to start of therapy) compared at end of radiation therapy (6 weeks later) ]
    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.

  2. Change in neurobehavioral outcome [ Time Frame: At baseline (prior to start of therapy) compared at end of medication trial (12 weeks later) ]
    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.

  3. Change in neurobehavioral outcome [ Time Frame: At baseline (prior to start of therapy) compared at follow-up (up to 1 year later) ]
    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.

  4. Frequency of memantine side effects [ Time Frame: From start of memantine/placebo therapy through end of therapy (up to 12 weeks later) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03194906


Contacts
Layout table for location contacts
Contact: Heather M. Conklin, PhD 866-278-5833 referralinfo@stjude.org

Locations
Layout table for location information
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Heather M Conklin, PhD         
Principal Investigator: Heather M. Conklin, PhD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Heather M. Conklin, PhD St. Jude Children's Research Hospital

Additional Information:
Layout table for additonal information
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT03194906     History of Changes
Other Study ID Numbers: MEMCRT
R21CA218625 ( U.S. NIH Grant/Contract )
NCI-2017-01279 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Jude Children's Research Hospital:
Pediatric oncology
Brain tumor
Low grade glioma
Cognitive late effects
Radiation therapy
Neuroprotection
Memantine
Additional relevant MeSH terms:
Layout table for MeSH terms
Craniopharyngioma
Adamantinoma
Brain Neoplasms
Ependymoma
Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Bone Neoplasms
Bone Diseases
Musculoskeletal Diseases
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents