A Phase 3 interventional study of Conventional Surgery and Questionnaire Administration in Malignant Solid Neoplasm and Metastatic Malignant Neoplasm in the Brain, sponsored by Mayo Clinic. Recruiting at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by Mayo Clinic · Phase 3, Interventional, and Treatment
This phase III trial studies the side effects and how well stereotactic radiosurgery (SRS) works before or after surgery in patients with tumors that has spread to the brain or that can be removed by surgery. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue.
PRIMARY OBJECTIVE:
I. To determine for patients with brain metastases meeting the inclusion criteria, whether there is an increase in the time to a composite endpoint of adverse outcomes including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis in patients who receive SRS prior to surgery as compared to patients who receive surgery prior to SRS.
SECONDARY OBJECTIVES:
I. To determine for patients with brain metastases whether there is improved overall survival for patients who receive SRS prior to surgery as compared to patients who receive SRS after surgery.
II. To determine for patients with brain metastases whether there are improved patient reported outcomes including quality of life for patients who receive SRS prior to surgery as compared to patients who receive SRS after surgery.
III. To determine if preoperative SRS increases rates of surgical morbidity including postoperative complications such as wound infection, need for longer hospital stays, or readmission compared to a surgery first approach for resectable brain metastases.
IV. To determine for patients with brain metastases whether there is a higher rate of completion of planned therapies for patients who receive SRS prior to surgery as compared to patients who receive surgery prior to SRS.
V. To determine for patients with brain metastases whether there is a shorter time to initiation or re-initiation of systemic therapy with pre-operative versus post-operative SRS.
VI. To determine for patients treated with pre-operative SRS whether there is a longer interval to regional progression, any central nervous system (CNS) progression or need for subsequent intracranial treatment compared to patients receiving post-operative SRS.
VII. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of radiation necrosis, including asymptomatic and symptomatic radiation necrosis.
VIII. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of local recurrence.
IX. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of leptomeningeal disease.
CORRELATIVE RESEARCH OBJECTIVES:
I. To determine the genetic and molecular alterations of brain metastases seen after radiation versus in the setting of resection alone, including early radiobiologic changes in tissue treated with SRS 24 to 48 hours prior, and to investigate detection rate of corresponding circulating deoxyribonucleic acid (DNA) and/or inflammatory markers in peripheral specimens.
II. To investigate the usefulness of biomarkers and response to radiation in predicting local control and outcomes.
III. To look at cell capture of tumor cells as well as cell free DNA in cerebrospinal fluid (CSF) sampled at the time of surgery, comparing patients receiving neoadjuvant treatment to those that have not.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients undergo surgery on day 1. Within 2 weeks, patients undergo stereotactic radiosurgery.
ARM B: Patients undergo stereotactic radiosurgery on day 1. Within 4 weeks, patients undergo surgery.
Patients also undergo a planning computed tomography (CT) or magnetic resonance imaging (MRI) before radiation and tissue and CSF sample collection at time of surgery. Additionally, patients undergo MRI and option blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 2 weeks, every 3-4 months for up to 2 years and then periodically for up to 3 years.
1,960 studies on the registry are indexed under Brain Neoplasms; 516 are open to participants now.
This study's planned enrollment of 140 is above the median of 40 across 1,458 interventional studies indexed under Brain Neoplasms.
Browse Brain Neoplasms studies →Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.
Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Any of the following:
Patients undergo surgery on day 1. Within 2 weeks, patients undergo stereotactic radiosurgery. Patients also undergo a planning CT or MRI before radiation and tissue and CSF sample collection at time of surgery. Additionally, patients undergo MRI and option blood sample collection throughout the study.
Procedure: Conventional Surgery · Other: Questionnaire Administration · Radiation: Stereotactic Radiosurgery · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Biospecimen Collection
Patients undergo stereotactic radiosurgery on day 1. Within 4 weeks, patients undergo surgery. Patients also undergo a planning CT or MRI before radiation and tissue and CSF sample collection at time of surgery and MRI throughout the study. Additionally, patients undergo MRI and option blood sample collection throughout the study.
Procedure: Conventional Surgery · Other: Questionnaire Administration · Radiation: Stereotactic Radiosurgery · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Procedure: Biospecimen Collection
Undergo surgery
Ancillary studies
Undergo stereotactic radiosurgery
Also known as: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery, SRS
Undergo CT
Also known as: CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan
Undergo MRI
Also known as: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, Structural MRI, sMRI
Undergo blood sample, tissue and CSF sample collection
Also known as: Biological Sample Collection, Specimen Collection
Central nervous system (CNS) composite endpoint event (CNS-CE event)
The CNS-CE event distributions will be estimated using the Kaplan-Meier method.
Time frame: Time from study randomization to documentation of the first CNS-CE event, assessed up to 5 years
Overall survival (OS)
Defined as the time from start of study therapy to death due to any cause.
Time frame: Up to 5 years
Incidence of adverse events
Will be graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The overall adverse event rates for grade 3 or higher adverse events will be compared using Chi-square or Fisher's exact tests between the 2 treatment groups.
Time frame: Up to 5 years post treatment
CNS-CE event free survival time adjusted for stratification factors
Cox-models will be used that incorporate the stratification factors to test for differences in treatment arms after adjusting for stratification factors listed in section 5.0.
Time frame: Up to 5 years
CNS-CE event free rate
The 6-month CNS-CE rates from the Kaplan-Meier analysis will be compared between the arms.
Time frame: At 6 months
Patient-reported outcome - Quality of Life (QOL)
QOL will be assessed via changes in the Functional Assessment of Cancer Therapy Scale-Brain (FACT-Br) Global score. The FACT-Br consists of 20 statements answered on a 5-point scale (not at all, a little bit, somewhat, quite a bit, or very much) related to quality of life over the past 7 days.
Time frame: Baseline to 6 months post treatment
Rate of completion of therapies
The rate of completion of planned therapies will be compared using Chi-square or Fisher's exact tests between the 2 treatment groups.
Time frame: Up to 5 years post treatment
Time to systemic therapy
Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.
Time frame: Time to initiation or re-initiation of systemic therapy with pre-operative versus post-operative SRS, assessed up to 5 years
Time to regional progression
Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.
Time frame: Up to 5 years post treatment
Time central nervous system (CNS) progression
Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.
Time frame: Up to 5 years post treatment
Time to subsequent treatment, including whole-brain radiotherapy (WBRT)
Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.
Time frame: Up to 5 years
Rate of neurosurgical morbidity
The rates of surgical morbidity including postoperative complications such as wound infection, need for longer hospital stays, or readmission will be compared using Chi-square or Fisher's exact tests between the 2 treatment groups.
Time frame: Up to 5 years post treatment
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Mayo Clinic