Brain MetastasesNASRSNCT03368625
A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases
A study testing Stereotactic Radiosurgery in people with Brain Metastases, run by University Health Network, Toronto at 2 sites in 2 countries.
Trial summary
This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS). 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
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 19 Mar 2018to 10 Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Lymphoma, small cell carcinoma, and seminoma are excluded
- A lesion appropriate for resection, not previously treated with SRS. Lesions should be > 2 cm and < 4 cm in largest dimension, and require resection ( e.g. due to mass effect or to obtain a tissue diagnosis). Index lesions will be treated with SRS and surgery, as outlined in the treatment section of the protocol.
- Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate NaSRS, e.g., the ability to lie flat in a stereotactic head frame.
- Any unresected lesions or lesions for which there is no planned immediate resection (non index lesions) must measure < 3.0 cm in maximal extent on the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. Unresected lesions will be treated with SRS as outlined in the treatment section of the protocol. .
- ECOG ≤ 2
- MRI confirmed 1-6 lesions, one of which is the index lesion. Each non-index lesion (up to 5) must measure ≤ 3.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection.
- Note: The pre-registration MRI may be obtained ≤ 35 days prior to enrolment.
Who cannot join
- Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
- pregnancy
- Prior cranial radiotherapy targeting the index lesion, or any prior WBRT.
- Inability to complete a MRI with contrast of the head, or a known allergy to gadolinium.
- Cytotoxic Chemotherapy within 7 days prior to SRS (molecularly targeted therapies , including immune-modulatory drugs, can be given within seven days of SRS at the discretion of the treating physician)
- Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor
Show all 11Show fewer
- Imaging Findings:
- Widespread definitive leptomeningeal metastasis.
- A brain metastasis that is located ≤ 2 mm of the optic chiasm
- Evidence of midline shift
- Fourth ventricular narrowing, concerning for hydrocephalus
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Germany1 site
Charité Universitätsmedizin Berlin, Campus Virchow Klinikum
Berlin, 13353
About this study
Official title: A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases
This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).
Read the detailed description
Recently, a novel treatment strategy for large brain metastases was described whereby lesions appropriate for resection were treated with a single fraction of SRS pre-operatively. In a retrospective analysis, of 51 lesions with a median tumor size of 3 cm, 1-year LC was 86%. This neoadjuvant approach resulted in lower rates of leptomeningeal failure (3 vs. 17%) and symptomatic radiation toxicity (1.5 vs. 14.6 %) compared to a comparative cohort of lesions treated with post-operative cavity boost SRS (POCBS).
Based on promising results, we believe that a prospective trial to establish the value of neoadjuvant SRS (NaSRS) for the treatment of BM appropriate for resection is warranted.
This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).
- Conditions
- Brain Metastases
- Being tested
- Stereotactic Radiosurgery
- Keywords
- Stereotactic Radiosurgery, Radiation, Surgery
- 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 RadiosurgeryRadiation
Stereotactic Radiosurgery before surgical resection of brain mets.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Other | Neoadjuvant SRS Receives: Radiation: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiation toxicity
The rate at 1 year of symptomatic (≥grade 2) radiation toxicity
Measured: 1 year
Secondary outcomes (5)
local control
1-year local control (PR+CR) of the index lesion resulting from NaSRS
Measured: 1 year
leptomeningeal disease
1-year rates of leptomeningeal disease
Measured: 1 year
Survival
Median survival
Measured: 5 years
progression-free survival
Measured: 2 years
overall survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2017
- Study start19 Mar 2018
- Primary completion10 Oct 2025
- Study completion10 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients with resectable brain mets will receive neoadjuvant stereotactic radiosurgery prior to surgical resection.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Shultz, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03368625
- Sponsor's protocol ID
- 17-5689
- Acronym
- NASRS
- Status last verified
- Mar 2026
- First submitted
- 4 Dec 2017
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Higazy R, Li D, Lau R, Millar BA, Laperriere N, Berlin A, Conrad T, Gutierrez-Valencia E, Zadeh G, Bernstein M, Kalyvas A, Spears J, Zips D, Vajkoczy P, Senger C, Acker G, Kongkham P, Shultz DB. Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: An International, Multicenter, Single-Arm Phase II Trial. Neurosurgery. 2025 Apr 14;97(4):793-800. doi: 10.1227/neu.0000000000003451.
PubMed 40227031
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases
- ClinicalTrials.gov ID
- NCT03368625
- Acronym / sponsor ID
- NASRS / 17-5689
- Conditions
- Brain Metastases
- Keywords
- Stereotactic Radiosurgery, Radiation, Surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 19 Mar 2018 (actual)
- Primary completion
- 10 Oct 2025 (actual)
- Study completion
- 10 Oct 2025 (actual)
- First posted
- 11 Dec 2017 (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 study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).
Detailed description
Recently, a novel treatment strategy for large brain metastases was described whereby lesions appropriate for resection were treated with a single fraction of SRS pre-operatively. In a retrospective analysis, of 51 lesions with a median tumor size of 3 cm, 1-year LC was 86%. This neoadjuvant approach resulted in lower rates of leptomeningeal failure (3 vs. 17%) and symptomatic radiation toxicity (1.5 vs. 14.6 %) compared to a comparative cohort of lesions treated with post-operative cavity boost SRS (POCBS).
Based on promising results, we believe that a prospective trial to establish the value of neoadjuvant SRS (NaSRS) for the treatment of BM appropriate for resection is warranted.
This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with resectable brain mets will receive neoadjuvant stereotactic radiosurgery prior to surgical resection.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Other | Radiation: Stereotactic RadiosurgeryNeoadjuvant SRS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Lymphoma, small cell carcinoma, and seminoma are excluded
- A lesion appropriate for resection, not previously treated with SRS. Lesions should be > 2 cm and < 4 cm in largest dimension, and require resection ( e.g. due to mass effect or to obtain a tissue diagnosis). Index lesions will be treated with SRS and surgery, as outlined in the treatment section of the protocol.
- Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate NaSRS, e.g., the ability to lie flat in a stereotactic head frame.
- Any unresected lesions or lesions for which there is no planned immediate resection (non index lesions) must measure < 3.0 cm in maximal extent on the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. Unresected lesions will be treated with SRS as outlined in the treatment section of the protocol. .
- ECOG ≤ 2
Key exclusion criteria (11 listed)
- Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
- pregnancy
- Prior cranial radiotherapy targeting the index lesion, or any prior WBRT.
- Inability to complete a MRI with contrast of the head, or a known allergy to gadolinium.
- Cytotoxic Chemotherapy within 7 days prior to SRS (molecularly targeted therapies , including immune-modulatory drugs, can be given within seven days of SRS at the discretion of the treating physician)
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 RadiosurgeryStereotactic Radiosurgery before surgical resection of brain mets. | Radiation | Arm 1 |
Primary outcome
Radiation toxicity
Time frame: 1 year
The rate at 1 year of symptomatic (≥grade 2) radiation toxicity
5 secondary outcomes
local control
Time frame: 1 year
leptomeningeal disease
Time frame: 1 year
Survival
Time frame: 5 years
progression-free survival
Time frame: 2 years
overall survival
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Derived from this study: PubMed 40227031Higazy R, Li D, Lau R, Millar BA, Laperriere N, Berlin A, Conrad T, Gutierrez-Valencia E, Zadeh G, Bernstein M, Kalyvas A, Spears J, Zips D, Vajkoczy P, Senger C, Acker G, Kongkham P, Shultz DB. Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: An International, Multicenter, Single-Arm Phase II Trial. Neurosurgery. 2025 Apr 14;97(4):793-800. doi: 10.1227/neu.0000000000003451.
Related trials for Brain Metastases
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
Epidural Hydroxyethyl Starch for Post-Dural Puncture Headache in Parturients
Parturients, Accidental Puncture of Dura During Anaesthesia
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
RecruitingPhase 2/3
RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive
HER2-positive Breast Cancer
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.
David Shultz, MD principal investigator
University Health Network, Toronto
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Radiosurgery in people with Brain Metastases, run by University Health Network, Toronto at 2 sites in 2 countries.
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 7 inclusion and 11 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: finished, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada, Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Radiation toxicity (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03368625, which also lists 1 linked publication.
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 4 Mar 2026.