Brain MetastasesNCT03775330
Radiosurgery With or Without Whole Brain Radiation for Multiple Metastases
An observational study of Brain Metastases, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
This clinical study is a parallel, prospective observational single-centre trial in patients presenting with 5 to 30 brain metastases. Patients to receive either stereotactic radiosurgery (SRS) alone or SRS plus whole brain radiation (WBRT) will be enrolled. 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?
- Stereotactic Radiosurgery (SRS) and Whole brain radiation (WBRT)
- Type of treatment
- Surgery or procedure
- How many people
- 126 participants
- Where
- 1 siteCanada
- Study dates
- 20 Oct 2020to Dec 2027
- Phase
- Observational
- 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
Study population: The participant population will be patients who have MRI-documented 5 to 30, inclusive, brain metastases at time of enrollment and who are suitable for receiving stereotactic radiosurgery (SRS) and whole brain radiation (WBRT), with or without hippocampal-avoidance.
Who may be able to join
- Histologic or cytologic diagnosis of non-hematopoietic malignancy (excluding germ cell malignancies and small cell carcinoma).
- Patients with ≥ 5 but ≤ 30 de novo brain metastases seen on a diagnostic-quality contrast-enhanced MRI obtained within 30 days prior to enrollment (or randomization if previously randomized). Patients who are found to have 31-50 metastatic lesions at the time of treatment planning may still participate in the study. Disease progression such that > 50 brain metastases are detected after initial MRI prior to enrollment but before SRS will be treated off-protocol as per discretion of the treating physician.
- Patients with ≥ 5 but ≤ 30 new brain metastases who have undergone prior SRS for 4 or less brain metastases with stable intracranial disease as per diagnostic MRI for at least 6 months post last course of SRS. Patients who are found to have 31-50 new metastatic lesions at the time of treatment planning may still participate in the study. Disease progression such that > 50 new brain metastases are detected after initial MRI prior to enrollment but before SRS will be treated off-protocol as per discretion of the treating physician.
- Age ≥ 18.
- Karnofsky Performance Status (KPS) ≥ 70.
- Baseline HVLT-R above ≥ 6
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- Patients must be able to tolerate WBRT, and all brain lesions must be eligible for treatment with SRS as determined by the radiation oncologist.
- Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
- Patient is able to read, speak, and understand (i.e. sufficiently fluent) English in order to allow completion and meaningful analyses of the neurocognitive tests and quality of life questionnaires.
- Patients must be accessible for treatment and follow up. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
- Patients who are on immunotherapy must have immunotherapy held at least 1 week before and after completion of radiotherapy. Other targeted agents/therapy must be held at least 1 day before and after SRS. Systemic chemotherapy must be held one week prior to treatment and re-started one week after treatment is complete.
- Protocol treatment is to begin within 4 weeks of patient enrollment (or randomization if previously randomized).
Who cannot join
- Patients with brain metastases resulting from germ cell malignancies, small cell carcinoma, or hematologic malignancies.
- Prior SRS for 5 or more brain metastases or any SRS for brain metastases within the last 6 months.
- Any prior WBRT or radiotherapy for brain metastases such that the study interventions cannot be delivered.
- Prior surgical resection of metastatic cancer from the brain.
- Patients with evidence of leptomeningeal disease.
- Patients who have a pacemaker or other contraindications, such that gadolinium-enhanced MRI cannot be performed or treatment cannot be delivered safely.
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- Patients who have received chemotherapy or immunotherapy within 1 week prior to administration of protocol radiotherapy or who are expected / planned to receive chemotherapy within one week of completing protocol radiotherapy.
- Patients with < 5 or > 30 de novo or new brain metastases at time of enrollment, or > 50 brain metastases at time of treatment planning.
- Patients who are pregnant (women of child-bearing age must have negative pregnancy urine test within 7 days of enrollment or randomization).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Parallel Prospective Observational Cohorts Evaluating Stereotactic Radiosurgery Alone (SRS) and Whole Brain Radiotherapy (WBRT) Plus SRS for Patients With 5 to 30 Brain Metastases
This clinical study is a parallel, prospective observational single-centre trial in patients presenting with 5 to 30 brain metastases. Patients to receive either stereotactic radiosurgery (SRS) alone or SRS plus whole brain radiation (WBRT) will be enrolled.
Read the detailed description
The current standard of care for patients with limited brain metastases (1 to 4) is stereotactic radiosurgery (SRS) alone. This has evolved from the traditional standard of care in treating patients with whole brain radiation (WBRT). Studies in patients with limited (less than 5) brain metastases have shown that WBRT is harmful with respect to neurocognition and does not improve patient survival compared to SRS alone. As a result, SRS alone now is considered the standard of care treatment for patients with limited metastases. However, there is a lack of high quality prospective randomized evidence on the role of SRS in patients with 5 or more brain metastases to guide treatment.
Therefore, this study seeks to prospectively compare SRS alone versus SRS plus WBRT in patients with 5 to 30 brain metastases.
- Conditions
- Brain Metastases
- Being tested
- Stereotactic Radiosurgery (SRS), Whole brain radiation (WBRT)
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Radiosurgery (SRS)Radiation
SRS or hypofractionated stereotactic radiation delivered via the Leksell Gammknife Perfexion/Icon radiosurgery system. Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions or 24-27 Gy in 3 fractions at the discretion of the radiation oncologist
Maximum diameter of metastasis (doses in single fraction):
≤ 2 cm: 15-20 Gy > 2 cm and ≤ 3 cm: 15-18 Gy > 3 cm and ≤ 4 cm: 15 Gy
Tumour location (doses in single fraction):
Brainstem: 15 Gy
Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions may be used for lesions > 2 cm at the discretion of the radiation oncologist
Note: SRS dosing reduced by 20% (for all prescriptions > 15 Gy) when patient is randomized to SRS + WBRT arm
Whole brain radiation (WBRT)Radiation
WBRT 20 Gy in 5 fractions or 30 Gy in 10 fractions at the discretion of the radiation oncologist
| Study group | Role | What they receive |
|---|---|---|
| SRS | Stereotactic radiosurgery Receives: Radiation: Stereotactic Radiosurgery (SRS) | |
| SRS plus WBRT | Stereotactic radiosurgery plus whole brain radiation Receives: Radiation: Stereotactic Radiosurgery (SRS); Radiation: Whole brain radiation (WBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurocognitive function
Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI)
Measured: 2 months post treatment
Secondary outcomes (10)
Neurocognitive function - HVLT-R
Hopkins Verbal Learning Test-Revised (HVLT-R) (Total Recall, Delayed Recall, Delayed Recognition)
Measured: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Trail Making Test
Trail Making Test (TMT, Part A and Part B)
Measured: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Controlled Oral Word Association
Controlled Oral Word Association (COWA)
Measured: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Clinical Trial Battery Composite
Clinical Trial Battery Composite (CTB COMP) score
Measured: 2 months, 4 months, 6 months, and 9 months
Local control of sites initially treated by SRS
Defined by the response criteria stipulated in the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria guideline
Measured: 2 months, 4 months, 6 months, and 9 months
Distant tumour control within the brain
Distant brain failure is defined as the appearance of one or more new lesions on a diagnostic-quality, contrast-enhanced MRI within the brain at sites other than those initially treated by SRS
Measured: 2 months, 4 months, 6 months, and 9 months
Overall central nervous system (CNS) response
Response will be recorded for each individual target lesion and for overall central nervous system (CNS) response as a composite of radiographical CNS target and non-target lesion responses, corticosteroid use, and clinical status defined as per RANO-BM criteria
Measured: 2 months, 4 months, 6 months, and 9 months
Overall survival
Response recorded for survival
Measured: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months
Measure of Quality of Life
Health-Related QoL as measured by Functional Assessment of Cancer Therapy - Brain (FACT-Br) instrument
Measured: 2 months, 4 months, 6 months, and 9 months
Incidence of Brain Salvage therapy During Follow-up
Number/proportion of patients requiring salvage therapy and type of salvage therapy, for progressive intracranial disease during follow-up
Measured: 2 months, 4 months, 6 months, and 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2018
- Study start20 Oct 2020
- Primary completionDec 2026 (estimated)
- Study completionDec 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 Sunnybrook Health Sciences CentreThe 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chia-Lin Tseng, M.D., Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03775330
- Sponsor's protocol ID
- BRAIN METS SRS
- Status last verified
- Apr 2026
- First submitted
- 21 Mar 2018
- Last updated
- 24 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 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Parallel Prospective Observational Cohorts Evaluating Stereotactic Radiosurgery Alone (SRS) and Whole Brain Radiotherapy (WBRT) Plus SRS for Patients With 5 to 30 Brain Metastases
- ClinicalTrials.gov ID
- NCT03775330
- Acronym / sponsor ID
- BRAIN METS SRS
- Conditions
- Brain Metastases
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 13 Dec 2018 (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 clinical study is a parallel, prospective observational single-centre trial in patients presenting with 5 to 30 brain metastases. Patients to receive either stereotactic radiosurgery (SRS) alone or SRS plus whole brain radiation (WBRT) will be enrolled.
Detailed description
The current standard of care for patients with limited brain metastases (1 to 4) is stereotactic radiosurgery (SRS) alone. This has evolved from the traditional standard of care in treating patients with whole brain radiation (WBRT). Studies in patients with limited (less than 5) brain metastases have shown that WBRT is harmful with respect to neurocognition and does not improve patient survival compared to SRS alone. As a result, SRS alone now is considered the standard of care treatment for patients with limited metastases. However, there is a lack of high quality prospective randomized evidence on the role of SRS in patients with 5 or more brain metastases to guide treatment.
Therefore, this study seeks to prospectively compare SRS alone versus SRS plus WBRT in patients with 5 to 30 brain metastases.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SRS | – | Radiation: Stereotactic Radiosurgery (SRS)Stereotactic radiosurgery |
| SRS plus WBRT | – | Radiation: Stereotactic Radiosurgery (SRS), Radiation: Whole brain radiation (WBRT)Stereotactic radiosurgery plus whole brain radiation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The participant population will be patients who have MRI-documented 5 to 30, inclusive, brain metastases at time of enrollment and who are suitable for receiving stereotactic radiosurgery (SRS) and whole brain radiation (WBRT), with or without hippocampal-avoidance.
Key inclusion criteria (12 listed)
- Histologic or cytologic diagnosis of non-hematopoietic malignancy (excluding germ cell malignancies and small cell carcinoma).
- Patients with ≥ 5 but ≤ 30 de novo brain metastases seen on a diagnostic-quality contrast-enhanced MRI obtained within 30 days prior to enrollment (or randomization if previously randomized). Patients who are found to have 31-50 metastatic lesions at the time of treatment planning may still participate in the study. Disease progression such that > 50 brain metastases are detected after initial MRI prior to enrollment but before SRS will be treated off-protocol as per discretion of the treating physician.
- Patients with ≥ 5 but ≤ 30 new brain metastases who have undergone prior SRS for 4 or less brain metastases with stable intracranial disease as per diagnostic MRI for at least 6 months post last course of SRS. Patients who are found to have 31-50 new metastatic lesions at the time of treatment planning may still participate in the study. Disease progression such that > 50 new brain metastases are detected after initial MRI prior to enrollment but before SRS will be treated off-protocol as per discretion of the treating physician.
- Age ≥ 18.
- Karnofsky Performance Status (KPS) ≥ 70.
Key exclusion criteria (9 listed)
- Patients with brain metastases resulting from germ cell malignancies, small cell carcinoma, or hematologic malignancies.
- Prior SRS for 5 or more brain metastases or any SRS for brain metastases within the last 6 months.
- Any prior WBRT or radiotherapy for brain metastases such that the study interventions cannot be delivered.
- Prior surgical resection of metastatic cancer from the brain.
- Patients with evidence of leptomeningeal disease.
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 |
|---|---|---|
| Stereotactic Radiosurgery (SRS)SRS or hypofractionated stereotactic radiation delivered via the Leksell Gammknife Perfexion/Icon radiosurgery system. Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions or 24-27 Gy in 3 fractions at the discretion of the radiation oncologist Maximum diameter of metastasis (doses in single fraction): ≤ 2 cm: 15-20 Gy > 2 cm and ≤ 3 cm: 15-18 Gy > 3 cm and ≤ 4 cm: 15 Gy Tumour location (doses in single fraction): Brainstem: 15 Gy Hypofractionated stereotactic radiotherapy 25-32.5 Gy in 5 fractions may be used for lesions > 2 cm at the discretion of the radiation oncologist Note: SRS dosing reduced by 20% (for all prescriptions > 15 Gy) when patient is randomized to SRS + WBRT arm | Radiation | SRS, SRS plus WBRT |
| Whole brain radiation (WBRT)WBRT 20 Gy in 5 fractions or 30 Gy in 10 fractions at the discretion of the radiation oncologist | Radiation | SRS plus WBRT |
Primary outcome
Neurocognitive function
Time frame: 2 months post treatment
Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI)
10 secondary outcomes
Neurocognitive function - HVLT-R
Time frame: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Trail Making Test
Time frame: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Controlled Oral Word Association
Time frame: 2 months, 4 months, 6 months, and 9 months
Neurocognitive function - Clinical Trial Battery Composite
Time frame: 2 months, 4 months, 6 months, and 9 months
Local control of sites initially treated by SRS
Time frame: 2 months, 4 months, 6 months, and 9 months
Distant tumour control within the brain
Time frame: 2 months, 4 months, 6 months, and 9 months
Overall central nervous system (CNS) response
Time frame: 2 months, 4 months, 6 months, and 9 months
Overall survival
Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months
Measure of Quality of Life
Time frame: 2 months, 4 months, 6 months, and 9 months
Incidence of Brain Salvage therapy During Follow-up
Time frame: 2 months, 4 months, 6 months, and 9 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 24 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. This study is not recruiting at the moment.
Chia-Lin Tseng, M.D. principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Metastases, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
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 12 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 24 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 Canada. 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurocognitive function (time frame: 2 months post treatment). 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 24 Apr 2026.