Clinical trial NCT06275035: Evaluation of Memantine in the Preservation of Memory and Neurocognition Following CSI
Official title: Memantine to Preserve Memory and Neurocognition Following Craniospinal Irradiation- A Randomised Controlled Trial (MEMENTO)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Neurocognitive Dysfunction
Lead sponsor: Tata Memorial Centre
Sponsor class: OTHER
First posted: 2024-02-23
Enrollment: 101
Sex: ALL
Minimum age (years): 5
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cognitive-deterioration-free survival at 2 years
timeFrame: 2 years
Secondary outcomes:
measure: Full-Scale Intelligence Quotient (FSIQ) in children
timeFrame: 7 years
measure: Overall survival (OS)
timeFrame: 7 years
measure: Academic performance by scholastic performance and grades
timeFrame: 7 years
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of Memantine
timeFrame: 2 years
measure: Progression-Free Survival (PFS)
timeFrame: 7 years
measure: Full-Scale Intelligence Quotient (FSIQ) in adults
timeFrame: 7 years
Other outcomes:
measure: Full Scale Intelligence Quotient change in subgroups
timeFrame: 7 years
measure: Radiological features of cognitive decline on Magnetic Resonance Imaging
timeFrame: 7 years
measure: Neuroinflammatory markers correlation with neurocognitive decline and survival
timeFrame: 7 years
Locations:
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
Study officials:
References:
citation: Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, Fox S, Suh JH, Roberge D, Kavadi V, Bentzen SM, Mehta MP, Watkins-Bruner D; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013 Oct;15(10):1429-37. doi: 10.1093/neuonc/not114. Epub 2013 Aug 16.
citation: Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, Bovi JA, Robinson C, Konski A, Khuntia D, Grosshans D, Benzinger TLS, Bruner D, Gilbert MR, Roberge D, Kundapur V, Devisetty K, Shah S, Usuki K, Anderson BM, Stea B, Yoon H, Li J, Laack NN, Kruser TJ, Chmura SJ, Shi W, Deshmukh S, Mehta MP, Kachnic LA; for NRG Oncology. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020 Apr 1;38(10):1019-1029. doi: 10.1200/JCO.19.02767. Epub 2020 Feb 14.