SMART Trial: Cognitive Sparing Brain Radiotherapy for Multiple Brain Metastases

Starting soon · Phase 2

Conditions studied: Brain Metastases From Solid Tumors

In brief

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.

Key facts

Study ID: NCT07505979
Run by: National Taiwan University Hospital
People needed: 90
Starts: 2026-04-01
Expected to finish: 2031-04-01
Last updated by the study team: 2026-04-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of brain metastases
Patients with brain metastasis outside a 5-mm margin around either hippocampus or corpus callosum on gadolinium contrast-enhanced MRI obtained within 30 days prior to registration
Patients with 6 or more active or progressive brain metastases that have not been treated by radiotherapy or radiosurgery
No evidence of diffuse leptomeningeal metastasis on gadolinium-enhanced MRI within 30 days prior registration
Age ≥ 18 years
Karnofsky Performance Status ≥ 60%
Life expectancy ≥ 6 months.
Women of childbearing potential and male participants must practice adequate contraception
Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent

You may not qualify if…

Prior radiotherapy to brain or radiosurgery to > 5 intracranial metastatic lesion(s)
Clinical diagnosis of symptomatic leptomeningeal metastsases
Contraindication to MR imaging such as implanted metal devices or foreign bodies, severe claustrophobia
Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
Uncontrolled active infection requiring intravenous antibiotics at the time of registration
Transmural myocardial infarction ≤ 6 months prior to registration
Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration
Life-threatening uncontrolled clinically significant cardiac arrhythmias
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
Uncontrolled psychiatric disorder
Will receive any other investigation agent or chemotherapy during cranial radiotherapy or radiosurgery
Current use of Memantine HCL or Allergy to Memantine HCL
Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic
Pregnant or breast-feeding women

Full record on ClinicalTrials.gov

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