Brain MetastasesPhase 2NCT05013892
NTS-WBRT in Brain Metastases
A Phase 2 study testing NTS-WBRT (normal tissue sparing whole brain radiation therapy) and Memantine in people with Brain Metastases, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research is being done to assess the quality of life and symptom burden in participants who receive (normal tissue sparing whole brain radiation therapy (NTS-WBRT). This research study involves: NTS-WBRT (normal tissue sparing whole brain radiation therapy) Memantine standard of care drug Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- NTS-WBRT (normal tissue sparing whole brain radiation therapy) and Memantine
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2022to 31 Dec 2027
- 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
- Any patient with a solid tumor diagnosis and any number of brain metastasis clinically indicated for cranial irradiation with whole brain radiation therapy
- Age ≥ 18
- Karnofsky Performance Status ≥ 70
- Prior stereotactic radiosurgery (SRS) permissible per physician discretion
- Prior craniotomy permissible per physician discretion. Protocol radiation therapy should be initiated ≥2 weeks after craniotomy.
- Prior partial brain radiation therapy permissible if target volume < 50% brain and per physician discretion
Show all 13Show fewer
- Expectant > 6 months survival
- Ability to understand and the willingness to sign a written informed consent document.
- Fluency in English, able to complete questionnaires and neurocognitive testing
- Ability to undergo MRI with gadolinium examination
- Ability to return for follow-up examinations throughout the course of this study for a maximum of 2 years after radiation treatment completion
- Any prior, concomitant, or post-radiotherapy systemic therapy is permitted at discretion of treating physicians
- Negative pregnancy test for premenopausal women
Who cannot join
- Leptomeningeal disease (by any one or more of clinical assessment, radiographic assessment, or cerebrospinal fluid study)
- Prior whole brain radiation therapy
- Pre-existing or current use of memantine or other NMDA antagonists
- Known allergy to contrast used in imaging studies and/or inability to have MRI imaging
- Uncontrolled intercurrent illness that could significantly affect baseline cognitive function as determined by the enrolling clinician, such as symptomatic congestive heart failure, unstable angina pectoris, prior CVA, significant uncontrolled epilepsy or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or unwilling to use appropriate contraception to prevent pregnancy during the time of radiation therapy
- Concurrent participation in an investigational systemic therapy protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Helen A Shih, MD,MS,MPH, 617-724-9627, hshih@mgh.harvard.edu
Helen A Shih, MD, MS, MPH
About this study
Official title: Phase II Trial of Normal Tissue Sparing Whole Brain Radiation Therapy (NTS-WBRT) in Patients With Brain Metastases
This research is being done to assess the quality of life and symptom burden in participants who receive (normal tissue sparing whole brain radiation therapy (NTS-WBRT).
This research study involves:
- NTS-WBRT (normal tissue sparing whole brain radiation therapy)
- Memantine standard of care drug
Read the detailed description
This is a Phase 2 trial testing the safety and effectiveness of NTS-WBRT (normal tissue sparing whole brain radiation therapy) in treating brain metastases.
NTS-WBRT is a targeted radiation therapy that further reduces radiation dose to tissue that does not need radiation therapy treatment.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
It is expected that about 41 people will take part in this research study.
- Conditions
- Brain Metastases
- Being tested
- NTS-WBRT (normal tissue sparing whole brain radiation therapy), Memantine
- Keywords
- Brain Metastases
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NTS-WBRT (normal tissue sparing whole brain radiation therapy)Radiation
Also called Radiation Therapy
Radiation
MemantineDrug
Also called Namenda, Namenda XR, Namenda XR Titration Pack
Capsule, taken orally
| Study group | Role | What they receive |
|---|---|---|
| NTS-WBRT (normal tissue sparing whole brain radiation therapy) + Memantine | Experimental | Participants will be randomly assigned to NTS-WBRT (normal tissue sparing whole brain radiation therapy) administration group and receive:
* NTS-WBRT for 5 days (Monday-Friday) for either 2 or 3 weeks.
* Memantine per standard of care, 1-2x daily for up to 24 weeks Specific participant administration schedules will be determined by study doctor Receives: Radiation: NTS-WBRT (normal tissue sparing whole brain radiation therapy); Drug: Memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Patient Reported Quality of Life for NTS-WBRT (normal tissue sparing whole brain radiation therapy)
Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.
Measured: 4 Months
Change in Patient Reported Symptom Burden for NTS-WBRT (normal tissue sparing whole brain radiation therapy)
Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.
Measured: 4 Months
Secondary outcomes (12)
Tumor local control Rates between NTS-WBRT+SIB and NTS-WBRT
Estimated by the cumulative incidence function treating death as a competing risk, compared using Gray's test
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Intracranial- Progression Free Survival (PFS) between NTS-WBRT+SIB and NTS-WBRT
Estimated using the Kaplan-Meier method, compared using the logrank test
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Overall survival (OS) between NTS-WBRT+SIB and NTS-WBRT
Estimated using the Kaplan-Meier method, compared using the logrank test
Measured: The date of randomization to the date of death, or otherwise censored at the last follow-up date for patients still alive up to 24 months
Change in Neurocognitive function between NTS-WBRT+SIB and NTS-WBRT
Assessed longitudinally by the HADS-D and HADS-A questionnaires
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Mood between NTS-WBRT+SIB and NTS-WBRT
Mixed effects models with treatment arm as a fixed effect will be used to compare changes in depression (HADS-D) and anxiety (HADS-A) scores over time
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Fatigue between NTS-WBRT+SIB and NTS-WBRT
Mixed effects models with treatment arm as a fixed effect will be used to compare changes in the fatigue score over time
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Neuroendocrine function between NTS-WBRT+SIB and NTS-WBRT
Estimated by the cumulative incidence function treating intracranial progression and death as competing risks; compared using Gray's test.
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Hearing between NTS-WBRT+SIB and NTS-WBRT Assessed by Pure Tone Average
Changes in pure tone average (PTA) from baseline to each subsequent assessment will be compared between treatment arms using Wilcox rank-sum test. Pure tone thresholds are found by presenting tones using standard headphones and methods in a sound treated booth. Pure tone thresholds will be tested by both bone (500, 1000, 2000 and 4000 Hz) and air conduction (250, 500, 1000, 2000, 3000, 4000, 6000, 8000, 10000, 12000, and 14000 Hz). Masking will be applied sufficient to determine the ear responsible for each value. The results of this testing will be used to determine the sensorineural hearing level. If significant conductive loss is found, bone conduction threshold will be used to report sensory ototoxicity. Threshold effects across frequency will be combined into a Pure Tone Average (PTA), defined as the average of audiometric thresholds at 500, 1000, 2000, and 4000. A significant decrease in Pure Tone Average is defined as an increase > 10 dB in relation to baseline threshold.
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Hearing between NTS-WBRT+SIB and NTS-WBRT Assessed by Word Recognition Score
Changes in word recognition score (WRS) from baseline to each subsequent assessment will be compared between treatment arms using Wilcox rank-sum test. Word recognition is defined as the percent correct on a standard, 50-item word list of English monosyllables: CID W-22, NU#6 or CNC. A significant decrease in word recognition is defined as a score exceeding the 95% critical difference from the table of Thornton and Raffin.
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Hearing between NTS-WBRT+SIB and NTS-WBRT Assessed by Otoacoustic Emissions
The rates of absent otoacoustic emissions (OAE) will be compared between treatment arms using Fisher's exact test. The OAE (Otoacoustic Emissions) test checks part of the inner ear's response to sound. Otoacoustic emissions are sounds given off by one small part of the cochlea when it is stimulated by soft clicking sounds. When the sound stimulates the cochlea, the outer hair cells vibrate. The vibration produces a nearly inaudible sound that echoes back into the middle ear. The results are either present or absent. Present OAEs are consistent with normal to near normal hearing. Absent OAEs may be a sign of a problem related to study treatment.
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Alopecia Rates between NTS-WBRT+SIB and NTS-WBRT
Assessed by patient report and visual inspection with documented photography; compared by Fisher's exact test
Measured: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
The number and proportion of adverse events, graded as defined by CTCAE version 5.0 will be tabulated by type and grade, compared using Fisher's exact test.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2021
- Study start8 Feb 2022
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by Massachusetts General 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Helen A. Shih, MD, Massachusetts General Hospital
- Investigators
- Helen A Shih, MD, MS, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05013892
- Sponsor's protocol ID
- 21-356
- Status last verified
- Apr 2026
- First submitted
- 6 Aug 2021
- Last updated
- 16 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Normal Tissue Sparing Whole Brain Radiation Therapy (NTS-WBRT) in Patients With Brain Metastases
- ClinicalTrials.gov ID
- NCT05013892
- Acronym / sponsor ID
- 21-356
- Conditions
- Brain Metastases
- Keywords
- Brain Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 8 Feb 2022 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 19 Aug 2021 (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.
This research is being done to assess the quality of life and symptom burden in participants who receive (normal tissue sparing whole brain radiation therapy (NTS-WBRT).
This research study involves:
- NTS-WBRT (normal tissue sparing whole brain radiation therapy)
- Memantine standard of care drug
Detailed description
This is a Phase 2 trial testing the safety and effectiveness of NTS-WBRT (normal tissue sparing whole brain radiation therapy) in treating brain metastases.
NTS-WBRT is a targeted radiation therapy that further reduces radiation dose to tissue that does not need radiation therapy treatment.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
It is expected that about 41 people will take part in this research study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NTS-WBRT (normal tissue sparing whole brain radiation therapy) + Memantine | Experimental | Radiation: NTS-WBRT (normal tissue sparing whole brain radiation therapy), Drug: MemantineParticipants will be randomly assigned to NTS-WBRT (normal tissue sparing whole brain radiation therapy) administration group and receive: * NTS-WBRT for 5 days (Monday-Friday) for either 2 or 3 weeks. * Memantine per standard of care, 1-2x daily for up to 24 weeks Specific participant administration schedules will be determined by study doctor |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Any patient with a solid tumor diagnosis and any number of brain metastasis clinically indicated for cranial irradiation with whole brain radiation therapy
- Age ≥ 18
- Karnofsky Performance Status ≥ 70
- Prior stereotactic radiosurgery (SRS) permissible per physician discretion
- Prior craniotomy permissible per physician discretion. Protocol radiation therapy should be initiated ≥2 weeks after craniotomy.
Key exclusion criteria (7 listed)
- Leptomeningeal disease (by any one or more of clinical assessment, radiographic assessment, or cerebrospinal fluid study)
- Prior whole brain radiation therapy
- Pre-existing or current use of memantine or other NMDA antagonists
- Known allergy to contrast used in imaging studies and/or inability to have MRI imaging
- Uncontrolled intercurrent illness that could significantly affect baseline cognitive function as determined by the enrolling clinician, such as symptomatic congestive heart failure, unstable angina pectoris, prior CVA, significant uncontrolled epilepsy or psychiatric illness/social situations that would limit compliance with study requirements
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 |
|---|---|---|
| NTS-WBRT (normal tissue sparing whole brain radiation therapy)Also: Radiation TherapyRadiation | Radiation | NTS-WBRT (normal tissue sparing whole brain radiation therapy) + Memantine |
| MemantineAlso: Namenda, Namenda XR, Namenda XR Titration PackCapsule, taken orally | Drug | NTS-WBRT (normal tissue sparing whole brain radiation therapy) + Memantine |
Primary outcome
Change in Patient Reported Quality of Life for NTS-WBRT (normal tissue sparing whole brain radiation therapy)
Time frame: 4 Months
Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.
Change in Patient Reported Symptom Burden for NTS-WBRT (normal tissue sparing whole brain radiation therapy)
Time frame: 4 Months
Assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. Score range is 0-200 and the higher the score, the better the outcome.
12 secondary outcomes
Tumor local control Rates between NTS-WBRT+SIB and NTS-WBRT
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Intracranial- Progression Free Survival (PFS) between NTS-WBRT+SIB and NTS-WBRT
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Overall survival (OS) between NTS-WBRT+SIB and NTS-WBRT
Time frame: The date of randomization to the date of death, or otherwise censored at the last follow-up date for patients still alive up to 24 months
Change in Neurocognitive function between NTS-WBRT+SIB and NTS-WBRT
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Mood between NTS-WBRT+SIB and NTS-WBRT
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Fatigue between NTS-WBRT+SIB and NTS-WBRT
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Neuroendocrine function between NTS-WBRT+SIB and NTS-WBRT
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Hearing between NTS-WBRT+SIB and NTS-WBRT Assessed by Pure Tone Average
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Hearing between NTS-WBRT+SIB and NTS-WBRT Assessed by Word Recognition Score
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Change in Hearing between NTS-WBRT+SIB and NTS-WBRT Assessed by Otoacoustic Emissions
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Alopecia Rates between NTS-WBRT+SIB and NTS-WBRT
Time frame: baseline, 2, 4, 6, 9, 12, 18 and 24 months
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
Time frame: Up to 24 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 16 Apr 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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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.
Helen A Shih, MD, MS, MPH principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NTS-WBRT (normal tissue sparing whole brain radiation therapy) and Memantine in people with Brain Metastases, run by Massachusetts General Hospital at 1 site in United States.
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 13 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Helen A Shih, MD, MS, MPH ((617) 724-9627, hshih@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Patient Reported Quality of Life for NTS-WBRT (normal tissue sparing whole brain radiation therapy) (time frame: 4 Months). The study lists 2 primary outcomes in all. 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 16 Apr 2026.