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Evaluation of Memantine in the Preservation of Memory and Neurocognition Following CSI

Phase 3
Recruiting
Conditions
Neurocognitive Dysfunction
Interventions
Registration Number
NCT06275035
Lead Sponsor
Tata Memorial Centre
Brief Summary

The goal of this clinical trial is to evaluate the role of memantine in preservation of memory and neurocognition in patients undergoing craniospinal irradiation. Participants will be randomised into two arms and the interventional arm will receive memantine along with the standard treatment. Researchers will compare the neurocognitive tests of participants in both the arms to see if memantine leads to significant preservation of memory and cognition post radiation therapy.

Detailed Description

Craniospinal irradiation (CSI) involving radiation (RT) of brain and spine, along with tumor-bed boost with or without chemotherapy, is the current standard treatment for medulloblastoma and other primitive embryonal tumors of the central nervous system (CNS). The delayed side effects following CSI include memory loss, hearing and balance difficulties, hormonal imbalance, and secondary cancers. Decline in memory severely affects the quality of life in long term survivors of these diseases. Hence, various strategies are being tried to prevent it. Memantine has been proven to effectively prevent the memory decline induced by RT. It is FDA-approved for Alzheimer's disease and is widely used in the children for several developmental disorders. With this study, we are trying to investigate the role of memantine in patients receiving CSI to prevent memory decline.

After screening for the study, eligible patients will be randomly allocated (by computerised system) to one of the two arms that are described as follows. Patients in the experimental arm (memantine) will be started on memantine, starting dose of the same will be 5mg once daily at bedtime for 1 week, followed by 5mg twice daily for 1 week, and finally increased to the full dose of 10 mg twice daily for 6 months. Patients will continue on radiation and chemotherapy (when indicated) as per schedule. All patients in the study will undergo neurocognitive evaluation, the time points for which will be pre-radiation (baseline), 6 months post-RT, 1-year post-RT, and annually after that for 5 years from radiation. Following completion of RT or treatment, standard follow-up protocols will include a clinical examination 3 monthly for the first 2 years, followed by 6 monthly visits till 5 years post-RT. No additional risk is expected from the current study other than the common side effects of the standard treatment. Based on the results from the study, if primary endpoints are achieved, it will establish the role of memantine in preventing memory decline from CSI, which can be used as a standard treatment measure to help patients in the future.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
101
Inclusion Criteria
  • Age at irradiation: 5 to 39 years
  • Planned for CSI (with or without boost dose) with or without systemic chemotherapy
  • Informed consent or assent taken
  • Karnofsky Performance Status / Lansky Performance Status ≥ 60
Exclusion Criteria
  • Re-irradiation
  • Prior exposure to memantine
  • Inability to undergo Wechsler test

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Experimental armMemantine Oral TabletParticipants in the experimental arm (memantine) will be started on memantine. The starting dose of memantine will be 5mg once daily at bedtime for 1 week, followed by 5mg twice daily for 1 week, and finally increased to the full dose of 10 mg twice daily for 6 months.
Primary Outcome Measures
NameTimeMethod
Cognitive-deterioration-free survival at 2 years2 years

Cognitive-deterioration-free survival at 2 years; defined by a drop of 5 points in any of Full Scale Intelligence Quotient (FSIQ), Verbal Intelligence Quotient (VIQ), or Performance Intelligence Quotient (PIQ) compared to baseline (pre-radiation) on Wechsler Adult Intelligence Scale (WAIS), and Wechsler Intelligence Scale for Children (WISC).

Secondary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS)7 years

Comparison of progression-free survival time in both arms

Full-Scale Intelligence Quotient (FSIQ) in adults7 years

The slope of decline of FSIQ with time as measured using age-appropriate neurocognitive test battery for adults (Wechsler Adult Intelligence Scale-WAIS)

Overall survival (OS)7 years

Comparison of survival outcomes in both the arms

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of Memantine2 years

Recording of any unexpected adverse drug reactions according to CTCAE v 5.0

Academic performance by scholastic performance and grades7 years

Comparison of scholastic performance as graded in school examinations in pediatric participants in both arms

Full-Scale Intelligence Quotient (FSIQ) in children7 years

The slope of decline of FSIQ with time as measured using age-appropriate neurocognitive test battery for children (Wechsler Intelligence Scale for Children- WISC)

Trial Locations

Locations (1)

Tata Memorial Hospital

🇮🇳

Mumbai, Maharashtra, India

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