NCT07505979

SMART Trial: Cognitive Sparing Brain Radiotherapy for Multiple Brain Metastases

Stereotactic RadioSurgery Versus Memantine Plus Cognitive Sparing or Hippocampal Avoidance Whole Brain RadioTherapy for Multiple Brain Metastases (SMART): A Phase II Randomized Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this phase II randomized trial is to determine if Stereotactic Radiosurgery (SRS) or Cognitive Sparing WBRT (CS-WBRT) better preserves neurocognitive function than standard Hippocampal Avoidance WBRT (HA-WBRT) in patients with multiple brain metastases ( $\\ge6$ lesions). The main questions it aims to answer are: * Which treatment best preserves cognitive function (memory and executive tasks) at 6 months post-intervention? * Can sparing the left hippocampus and corpus callosum (CS-WBRT) or using focal SRS reduce cognitive decline compared to bilateral sparing? Comparison Groups Researchers will compare three arms to evaluate their impact on cognition and disease control: * Arm A (SRS): Focal high-dose radiation (15-20 Gy in 1 fraction) to intracranial lesions. * Arm B (CS-WBRT): Whole-brain radiation (30 Gy in 10 fractions) sparing the left hippocampus and corpus callosum plus Memantine. * Arm C (HA-WBRT): Whole-brain radiation (30 Gy in 10 fractions) with bilateral hippocampal avoidance plus Memantine. Participant Tasks Participants will: * Complete neurocognitive and neuropsychological tests (HVLT-R, TMT, COWAT, CANTAB) at baseline and follow-up. * Undergo contrast-enhanced brain MRI for planning and tracking tumor progression. * Take Memantine HCL daily for 24 weeks if assigned to the WBRT arms (B or C). * Provide blood samples for biomarker and genetic analysis (e.g., APOE, Tau). * Undergo olfactory function testing and complete quality-of-life questionnaires.

Conditions

• Brain Metastases From Solid Tumors

Interventions

Type	Name	Description
RADIATION	SRS	Focal high-dose radiation (15-20 Gy in 1 fraction) to intracranial lesions
RADIATION	CS-WBRT	Conformal Whole Brain Radiotherapy 3000 cGy in 10 fractions with Left Hippocampal Avoidance \& Corpus Callosum Sparing using RapidArc
RADIATION	HA-WBRT	Conformal Whole Brain Radiotherapy 3000 cGy in 10 fractions with Bilateral Hippocampal Avoidance using RapidArc

Timeline

• Start date: 2026-04-01
• Primary completion: 2029-04-01
• Completion: 2031-04-01
• First posted: 2026-04-01
• Last updated: 2026-04-13