Brain MetastasesNCT04545814
Analyzing Preoperative Stereotactic Radiosurgery With Gamma Knife Icon for Brain Metastases
A study testing Stereotactic Radiosurgery, Surgical Resection and Magnetic Resonance Imaging in people with Brain Metastases, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a single-arm, single-center pilot study in which 10 patients with one to four brain metastases diagnosed on brain magnetic resonance imaging (MRI) within the past 30 days will be evaluated for study eligibility and enrolled as appropriate. 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, Surgical Resection and Magnetic Resonance Imaging
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2021to 22 Aug 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Voluntary written consent must be given before performance of any study related procedure that's is not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female or Male subject's ≥ 18 years old at the time of informed consent.
- Radiographically confirmed solid tumor brain metastases.
- Criteria for surgical resection of at least one metastasis per neurosurgeon discretion.
- Stereotactic radiosurgery candidate per radiation oncologist discretion.
- A diagnostic MRI Brain or CT Head demonstrating the presence of 1-4 solid tumor brain metastases and lesion to be resected no more than 5 cm in any direction, performed within 30 days prior to stereotactic radiosurgery.
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- For known and unknown primary, diagnosis-specific graded prognostic assessment (ds-GPA) estimated median survival no less than 6 months.
- Surgical resection able to be performed within 1-10 days after radiosurgery.
- Patients currently on cytotoxic chemotherapy or immunotherapy are eligible, not including anti-vascular endothelial growth factor (anti-VEGF) therapy.
- Female subjects who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last study Intervention (female and male condoms should not be used together), OR ii. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
- Male subjects, even if surgically sterilized (ie, status post-vasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period from the time of signing the informed consent through and through 4 months after the last study Intervention (female and male condoms should not be used together), OR
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
Who cannot join
- Patients who received anti-VEGF therapy within 6 weeks prior to enrollment, as there is increased risk of fatal brain hemorrhage with surgical resection.
- Major medical illnesses or psychiatric impairments, which in the investigator's opinion will prevent administration or completion of the protocol therapy and/or interfere with surveillance.
- Patients with more than 4 brain metastases on MRI Brain.
- Lesion to be resected is more than 5 cm in any dimension.
- Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF) evaluation.
- Previous whole brain radiation therapy.
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- Previous radiation therapy to the lesion to be resected.
- Planned adjuvant focal therapy including additional radiation therapy to the brain.
- Not a surgical candidate per neurosurgeon discretion.
- Not a stereotactic radiosurgery candidate per radiation oncologist discretion.
- Surgery unable to be performed between 1 - 10 days after radiosurgery.
- Women who are pregnant or nursing as treatment involves unforeseeable risks to the fetus or child.
- Patients who have a known or unknown primary and have an estimated median survival of less than 6 months per ds-GPA.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert Hospital & Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Pilot Study Analyzing Preoperative Stereotactic Radiosurgery (SRS) With Gamma Knife (GK) for Brain Metastases
This is a single-arm, single-center pilot study in which 10 patients with one to four brain metastases diagnosed on brain magnetic resonance imaging (MRI) within the past 30 days will be evaluated for study eligibility and enrolled as appropriate.
Read the detailed description
INTERVENTION: Enrolled patients will receive stereotactic radiosurgery (SRS) to all metastases followed by surgical resection of resectable metastases within one to 10 days following SRS. Pathologic specimens will be analyzed, and the patient will enter a standard pattern of surveillance (brain MRI every three months for two years).
STUDY RATIONALE: Given the increased risk of leptomeningeal failure with surgery followed by SRS as well as the risk of radiation necrosis, new paradigms in therapy delivery and sequencing are being explored. Areas of investigation include optimization of target volume, marginal expansion, multi-fractionation, timeliness of SRS after surgery, and delivery of SRS prior to surgical resection. In theory, advantages of preoperative SRS include better target delineation, sterilization of tumor cells prior to surgical disruption of the tumor, vascular supply, and cerebrospinal fluid (CSF) spaces, and resection of tissue that would otherwise be at risk of radiation necrosis.
In 2014, Asher, et al. reported that the use of neoadjuvant SRS prior to surgery was both safe and effective (even for metastases >3 cm) with no reported leptomeningeal recurrences or radiation necrosis. More recently, Patel et al. performed a retrospective comparison of preoperative versus postoperative SRS and reported no difference in local control, distant brain failure, or overall survival. Furthermore, the authors reported significantly lower rates of leptomeningeal carcinomatosis and radiation necrosis with preoperative SRS.
Huff, et al. recently published a protocol for a phase II prospective trial designed to compare outcomes using preoperative SRS versus historically cited outcomes for postoperative SRS. This pilot study mirrors this design and aims to confirm study feasibility and to assess local control, central nervous system (CNS) progression-free survival, overall survival, rates of leptomeningeal spread, rates of radiation necrosis, and quality of life measures with the use of preoperative SRS.
- Conditions
- Brain Metastases
- Being tested
- Stereotactic Radiosurgery, Surgical Resection, Magnetic Resonance Imaging
- Keywords
- brain metastases, Gamma Knife, 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.
Stereotactic RadiosurgeryDevice
Also called SRS
Maximum Tumor Diameter ≤ 2 cm = 20-24 Gy; Maximum Tumor Diameter 2.1-3.0 cm = 18 Gy; Maximum Tumor Diameter 3.1-5.0 cm = 15 Gy
Surgical ResectionProcedure or surgery
Enrolled patients will receive GK-SRS to all metastases followed by surgical resection of resectable metastases within one to10 days following GK-SRS.
Magnetic Resonance ImagingDevice
Following surgical resection, the patient will enter a standard pattern of surveillance (brain MRI every three months for two years).
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Radiosurgery | Experimental | SRS will be delivered utilizing gamma knife or linear accelerator-based techniques. Receives: Device: Stereotactic Radiosurgery; Procedure: Surgical Resection; Device: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Subjects Undergoing Resection Following SRS.
All subjects undergoing resection following SRS will be documented.
Measured: 10 days following SRS
The Number of Subjects With no Identifiable Disease Following Resection.
Identifiable disease will be determined by post-treatment MRI of the brain.
Measured: 20 months
Secondary outcomes (5)
The Number of Subjects Achieving CNS Progression-free Survival.
Progression/progressive disease for this outcome measure was assessed at the index lesion using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Lesions must be contrast-enhancing on T1-weighted MRI, with at least one dimension ≥ 10 mm and visible on ≥ 2 axial slices. Progression is defined as a ≥ 20% increase in the sum of diameters (with a ≥ 5 mm absolute increase) or new lesions. Subjects will be evaluated at six, 12 and 18 months.
Measured: 6, 12 and 18 months
The Number of Subjects Achieving Overall Survival.
The number of subjects alive at six, 12 and 18 months following surgical resection.
Measured: 6, 12 and 18 months
The Number of Subjects With Leptomeningeal Carcinomatosis Using Preoperative SRS.
The number of subjects with this diagnosis will be documented.
Measured: Two years
The Number of Subjects With Radiation Necrosis.
Radiation necrosis will be determined by radiographic appearance on posttreatment MRI. The number of patients with radiation necrosis will be documented.
Measured: Two years
The Number of Subjects Reporting a High Quality of Life.
Quality of life will be measured by the MD Anderson Symptom Inventory for brain tumor (MDASI-BT). The MDASI assesses the severity of symptoms at their worst in the last. 24 hours on a 0-10 numeric rating scale (NRS), with 0 being "not present" and 10 being "as bad as you can imagine." Health-related quality of life was assessed using the EQ-5D-5L instrument.
While not identical to the MDASI, the EQ-5D-5L has been shown to correlate strongly with symptom burden and overall quality-of-life measures commonly used in oncology populations and was used here as a pragmatic surrogate for global quality-of-life assessment.
A High Quality of Life was defined a priori as an EQ-5D-5L visual analog scale (VAS) score ≥80, reflecting a high level of self-reported overall health status. This threshold was selected to represent preserved or favorable quality of life and to allow for consistent longitudinal reporting across study time points.
Measured: Every 3 months until two years; 3, 6, 9, 12, 15, and 18 months reported
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2020
- Study start15 Jan 2021
- Primary completion22 Aug 2024
- Study completion22 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)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 Medical College of WisconsinThe 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
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Straza, MD, PhD, Medical College of Wisconsin
- Investigators
- Michael Straza, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04545814
- Sponsor's protocol ID
- PRO00038835
- Status last verified
- Mar 2026
- First submitted
- 4 Sep 2020
- Last updated
- 24 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Asher AL, Burri SH, Wiggins WF, Kelly RP, Boltes MO, Mehrlich M, Norton HJ, Fraser RW. A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):899-906. doi: 10.1016/j.ijrobp.2013.12.013.
PubMed 24606851Patel KR, Burri SH, Asher AL, Crocker IR, Fraser RW, Zhang C, Chen Z, Kandula S, Zhong J, Press RH, Olson JJ, Oyesiku NM, Wait SD, Curran WJ, Shu HK, Prabhu RS. Comparing Preoperative With Postoperative Stereotactic Radiosurgery for Resectable Brain Metastases: A Multi-institutional Analysis. Neurosurgery. 2016 Aug;79(2):279-85. doi: 10.1227/NEU.0000000000001096.
PubMed 26528673Huff WX, Agrawal N, Shapiro S, Miller J, Kulwin C, Shah M, Savage JJ, Payner T, Vortmeyer A, Watson G, Dey M. Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial. Radiat Oncol. 2018 Dec 20;13(1):252. doi: 10.1186/s13014-018-1178-8.
PubMed 30572923
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Analyzing Preoperative Stereotactic Radiosurgery (SRS) With Gamma Knife (GK) for Brain Metastases
- ClinicalTrials.gov ID
- NCT04545814
- Acronym / sponsor ID
- PRO00038835
- Conditions
- Brain Metastases
- Keywords
- brain metastases, Gamma Knife, Stereotactic Radiosurgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 15 Jan 2021 (actual)
- Primary completion
- 22 Aug 2024 (actual)
- Study completion
- 22 Aug 2024 (actual)
- First posted
- 11 Sep 2020 (actual)
- Results
- Posted 24 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm, single-center pilot study in which 10 patients with one to four brain metastases diagnosed on brain magnetic resonance imaging (MRI) within the past 30 days will be evaluated for study eligibility and enrolled as appropriate.
Detailed description
INTERVENTION: Enrolled patients will receive stereotactic radiosurgery (SRS) to all metastases followed by surgical resection of resectable metastases within one to 10 days following SRS. Pathologic specimens will be analyzed, and the patient will enter a standard pattern of surveillance (brain MRI every three months for two years).
STUDY RATIONALE: Given the increased risk of leptomeningeal failure with surgery followed by SRS as well as the risk of radiation necrosis, new paradigms in therapy delivery and sequencing are being explored. Areas of investigation include optimization of target volume, marginal expansion, multi-fractionation, timeliness of SRS after surgery, and delivery of SRS prior to surgical resection. In theory, advantages of preoperative SRS include better target delineation, sterilization of tumor cells prior to surgical disruption of the tumor, vascular supply, and cerebrospinal fluid (CSF) spaces, and resection of tissue that would otherwise be at risk of radiation necrosis.
In 2014, Asher, et al. reported that the use of neoadjuvant SRS prior to surgery was both safe and effective (even for metastases >3 cm) with no reported leptomeningeal recurrences or radiation necrosis. More recently, Patel et al. performed a retrospective comparison of preoperative versus postoperative SRS and reported no difference in local control, distant brain failure, or overall survival. Furthermore, the authors reported significantly lower rates of leptomeningeal carcinomatosis and radiation necrosis with preoperative SRS.
Huff, et al. recently published a protocol for a phase II prospective trial designed to compare outcomes using preoperative SRS versus historically cited outcomes for postoperative SRS. This pilot study mirrors this design and aims to confirm study feasibility and to assess local control, central nervous system (CNS) progression-free survival, overall survival, rates of leptomeningeal spread, rates of radiation necrosis, and quality of life measures with the use of preoperative SRS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Radiosurgery | Experimental | Device: Stereotactic Radiosurgery, Procedure: Surgical Resection, Device: Magnetic Resonance ImagingSRS will be delivered utilizing gamma knife or linear accelerator-based techniques. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Voluntary written consent must be given before performance of any study related procedure that's is not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female or Male subject's ≥ 18 years old at the time of informed consent.
- Radiographically confirmed solid tumor brain metastases.
- Criteria for surgical resection of at least one metastasis per neurosurgeon discretion.
- Stereotactic radiosurgery candidate per radiation oncologist discretion.
Key exclusion criteria (13 listed)
- Patients who received anti-VEGF therapy within 6 weeks prior to enrollment, as there is increased risk of fatal brain hemorrhage with surgical resection.
- Major medical illnesses or psychiatric impairments, which in the investigator's opinion will prevent administration or completion of the protocol therapy and/or interfere with surveillance.
- Patients with more than 4 brain metastases on MRI Brain.
- Lesion to be resected is more than 5 cm in any dimension.
- Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF) evaluation.
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 RadiosurgeryAlso: SRSMaximum Tumor Diameter ≤ 2 cm = 20-24 Gy; Maximum Tumor Diameter 2.1-3.0 cm = 18 Gy; Maximum Tumor Diameter 3.1-5.0 cm = 15 Gy | Device | Stereotactic Radiosurgery |
| Surgical ResectionEnrolled patients will receive GK-SRS to all metastases followed by surgical resection of resectable metastases within one to10 days following GK-SRS. | Procedure or surgery | Stereotactic Radiosurgery |
| Magnetic Resonance ImagingFollowing surgical resection, the patient will enter a standard pattern of surveillance (brain MRI every three months for two years). | Device | Stereotactic Radiosurgery |
Primary outcome
The Number of Subjects Undergoing Resection Following SRS.
Time frame: 10 days following SRS
All subjects undergoing resection following SRS will be documented.
The Number of Subjects With no Identifiable Disease Following Resection.
Time frame: 20 months
Identifiable disease will be determined by post-treatment MRI of the brain.
5 secondary outcomes
The Number of Subjects Achieving CNS Progression-free Survival.
Time frame: 6, 12 and 18 months
The Number of Subjects Achieving Overall Survival.
Time frame: 6, 12 and 18 months
The Number of Subjects With Leptomeningeal Carcinomatosis Using Preoperative SRS.
Time frame: Two years
The Number of Subjects With Radiation Necrosis.
Time frame: Two years
The Number of Subjects Reporting a High Quality of Life.
Time frame: Every 3 months until two years; 3, 6, 9, 12, 15, and 18 months reported
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24606851Asher AL, Burri SH, Wiggins WF, Kelly RP, Boltes MO, Mehrlich M, Norton HJ, Fraser RW. A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys. 2014 Mar 15;88(4):899-906. doi: 10.1016/j.ijrobp.2013.12.013.
- Background: PubMed 26528673Patel KR, Burri SH, Asher AL, Crocker IR, Fraser RW, Zhang C, Chen Z, Kandula S, Zhong J, Press RH, Olson JJ, Oyesiku NM, Wait SD, Curran WJ, Shu HK, Prabhu RS. Comparing Preoperative With Postoperative Stereotactic Radiosurgery for Resectable Brain Metastases: A Multi-institutional Analysis. Neurosurgery. 2016 Aug;79(2):279-85. doi: 10.1227/NEU.0000000000001096.
- Background: PubMed 30572923Huff WX, Agrawal N, Shapiro S, Miller J, Kulwin C, Shah M, Savage JJ, Payner T, Vortmeyer A, Watson G, Dey M. Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial. Radiat Oncol. 2018 Dec 20;13(1):252. doi: 10.1186/s13014-018-1178-8.
- 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.
Michael Straza, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Radiosurgery, Surgical Resection and Magnetic Resonance Imaging in people with Brain Metastases, run by Medical College of Wisconsin 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 16 inclusion and 13 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 24 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 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Subjects Undergoing Resection Following SRS. (time frame: 10 days following SRS). 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?
On the ClinicalTrials.gov record for NCT04545814, which also lists 3 linked publications.
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 Mar 2026.