Brain Metastases From Solid TumorsPhase 2NCT07505979
SMART Trial: Cognitive Sparing Brain Radiotherapy for Multiple Brain Metastases
A Phase 2 study testing SRS, CS-WBRT and HA-WBRT in people with Brain Metastases From Solid Tumors, run by National Taiwan University Hospital.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases From Solid Tumors
- What is being tested?
- SRS, CS-WBRT and HA-WBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- No sites listed yet
- Study dates
- Apr 2026to Apr 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Stereotactic RadioSurgery Versus Memantine Plus Cognitive Sparing or Hippocampal Avoidance Whole Brain RadioTherapy for Multiple Brain Metastases (SMART): A Phase II Randomized Trial
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:
Read more
- 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
- Being tested
- SRS, CS-WBRT, HA-WBRT
- Keywords
- Brain metastases, Cognitive Preservation, Hippocampal Avoidance Whole Brain Radiotherapy, Stereotactic Radiosurgery
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRSRadiation
Focal high-dose radiation (15-20 Gy in 1 fraction) to intracranial lesions
CS-WBRTRadiation
Conformal Whole Brain Radiotherapy 3000 cGy in 10 fractions with Left Hippocampal Avoidance \& Corpus Callosum Sparing using RapidArc
HA-WBRTRadiation
Conformal Whole Brain Radiotherapy 3000 cGy in 10 fractions with Bilateral Hippocampal Avoidance using RapidArc
| Study group | Role | What they receive |
|---|---|---|
| SRS | Experimental | Not described Receives: Radiation: SRS |
| CS-WBRT | Experimental | Not described Receives: Radiation: CS-WBRT |
| HA-WBRT | Active comparator | Not described Receives: Radiation: HA-WBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preservation in neurocognitive function at 6 months after the start of brain radiotherapy for patients with multiple brain metastases
The primary endpoint is defined as the z-scores of changes in HVLT-R memory score, and CANTAB® tasks at 6 months after the start of cranial radiotherapy or radiosurgery for multiple brain metastases. Investigators hypothesize that at least one of the three treatment arms will outperform the others in preserving neurocognitive function at 6 months
Measured: From enrollment to 6 months after the start of brain radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2026
- Study startApr 2026 (estimated)
- Primary completionApr 2029 (estimated)
- Study completionApr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Metastases From Solid TumorsStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07505979
- Sponsor's protocol ID
- 202510164MIFD
- Status last verified
- Mar 2026
- First submitted
- 24 Mar 2026
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stereotactic RadioSurgery Versus Memantine Plus Cognitive Sparing or Hippocampal Avoidance Whole Brain RadioTherapy for Multiple Brain Metastases (SMART): A Phase II Randomized Trial
- ClinicalTrials.gov ID
- NCT07505979
- Acronym / sponsor ID
- 202510164MIFD
- Conditions
- Brain Metastases From Solid Tumors
- Keywords
- Brain metastases, Cognitive Preservation, Hippocampal Avoidance Whole Brain Radiotherapy, Stereotactic Radiosurgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Apr 2026 (estimated)
- Primary completion
- Apr 2029 (estimated)
- Study completion
- Apr 2031 (estimated)
- First posted
- 1 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SRS | Experimental | Radiation: SRS |
| CS-WBRT | Experimental | Radiation: CS-WBRT |
| HA-WBRT | Active comparator | Radiation: HA-WBRT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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:
- Will receive any other investigation agent or chemotherapy during cranial radiotherapy or radiosurgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SRSFocal high-dose radiation (15-20 Gy in 1 fraction) to intracranial lesions | Radiation | SRS |
| CS-WBRTConformal Whole Brain Radiotherapy 3000 cGy in 10 fractions with Left Hippocampal Avoidance \& Corpus Callosum Sparing using RapidArc | Radiation | CS-WBRT |
| HA-WBRTConformal Whole Brain Radiotherapy 3000 cGy in 10 fractions with Bilateral Hippocampal Avoidance using RapidArc | Radiation | HA-WBRT |
Primary outcome
Preservation in neurocognitive function at 6 months after the start of brain radiotherapy for patients with multiple brain metastases
Time frame: From enrollment to 6 months after the start of brain radiotherapy
The primary endpoint is defined as the z-scores of changes in HVLT-R memory score, and CANTAB® tasks at 6 months after the start of cranial radiotherapy or radiosurgery for multiple brain metastases. Investigators hypothesize that at least one of the three treatment arms will outperform the others in preserving neurocognitive function at 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SRS, CS-WBRT and HA-WBRT in people with Brain Metastases From Solid Tumors, run by National Taiwan University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wen-Chi Yang, MD, PhD (+886912545812, claireds23@ntuh.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preservation in neurocognitive function at 6 months after the start of brain radiotherapy for patients with multiple brain metastases (time frame: From enrollment to 6 months after the start of brain radiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.