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Malignant Solid NeoplasmPhase 3NCT03750227

Pre-Operative or Post-Operative Stereotactic Radiosurgery in Treating Patients With Operative Metastatic Brain Tumors

A Phase 3 study testing Conventional Surgery, Questionnaire Administration and Stereotactic Radiosurgery in people with Malignant Solid Neoplasm and Metastatic Malignant Neoplasm in the Brain, run by Mayo Clinic at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Conventional Surgery, Questionnaire Administration and Stereotactic Radiosurgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
4 sitesUnited States
Study dates
19 Nov 2018to 8 Nov 2030
Phase
Phase 3
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

  • Age >= 18 years
  • Histological or cytological confirmation of solid tumor malignancy and/or clinical history of known or suspected metastatic disease with an intraparenchymal brain tumor consistent with brain metastasis based on clinical and radiologic findings
  • Clinical indication for surgical resection of one brain metastasis based on neurosurgery recommendation and patient deemed a surgical candidate
  • Clinical indication and plan for stereotactic radiosurgery to all known brain lesions requiring treatment (=< 10 metastases)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
  • Provide written informed consent or have a legally authorized representative who is responsible for the care and well-being of the potential study participant, provide consent
  • Willing to continue follow-up visits, either at the enrolling institution or with a local medical doctor as clinically appropriate, and according to the study timeline. Clinical notes and digital copies of imaging must be provided to the enrolling site if follow-up is done externally

Who cannot join

  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy. * NOTE: Patients known to be HIV, but without clinical evidence of an immunocompromised state, are eligible for this trial
Show all 18Show fewer
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Prior open neurosurgery for malignancy
  • Known or clinically suspected primary germ cell tumor, small cell carcinoma, or lymphoma
  • History of whole brain radiation therapy (WBRT)
  • Known allergy to gadolinium, pacemaker, or other contraindication such as metal implant that is not safe for MRI. Patients with MRI-compatible implants including MRI compatible pacemakers are eligible
  • Leptomeningeal metastasis/disease
  • A brain metastasis that is located =< 5 mm of the optic chiasm
  • Any brain metastasis > 5 cm in size
  • > 10 brain metastases
  • Indication for surgical resection of >= 2 brain metastases
  • Indication for long-term (anticipated greater than 4 weeks) 4 mg dexamethasone equivalent of steroids or bevacizumab
  • Actively enrolled on another brain metastases trial that is assessing the efficacy of either radiation or surgical interventions

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Clinical Trials Referral Office contact

855-776-0015

mayocliniccancerstudies@mayo.edu

United States4 sites, 4 recruiting
  • NIH Clinical Center

    Bethesda, Maryland, 20892

    DeeDee K. Smart, M.D., Ph.D., 301-496-5457, smartd@mail.nih.gov

    DeeDee K. Smart, M.D., Ph.D.

    Recruiting
  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

    Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Daniel Trifiletti, M.D.

    Recruiting
  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Elizabeth S. Yan, M.D.

    Recruiting
  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

    Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Sujay A. Vora, M.D.

    Recruiting

Other trials in United States

About this study

Official title: Pre-Operative vs. Post-Operative Stereotactic Radiosurgery for Operative Metastatic Brain Tumors

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Being tested
Conventional Surgery, Questionnaire Administration, Stereotactic Radiosurgery, Computed Tomography, Magnetic Resonance Imaging
Medical subject headings
Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Conventional SurgeryProcedure or surgery

    Undergo surgery

  • Questionnaire AdministrationOther

    Ancillary studies

  • Stereotactic RadiosurgeryRadiation

    Also called Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy

    Undergo stereotactic radiosurgery

  • Computed TomographyProcedure or surgery

    Also called CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MRI

    Undergo MRI

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Specimen Collection

    Undergo blood sample, tissue and CSF sample collection

Study groups in NCT03750227
Study groupRoleWhat they receive
Arm A (Post-operative SRS)Active comparatorPatients 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.
Receives: Procedure: Conventional Surgery; Other: Questionnaire Administration; Radiation: Stereotactic Radiosurgery; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection
Arm B (Pre-operative SRS)ExperimentalPatients 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.
Receives: Procedure: Conventional Surgery; Other: Questionnaire Administration; Radiation: Stereotactic Radiosurgery; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Central nervous system (CNS) composite endpoint event (CNS-CE event)

    The CNS-CE event distributions will be estimated using the Kaplan-Meier method.

    Measured: Time from study randomization to documentation of the first CNS-CE event, assessed up to 5 years

Secondary outcomes (11)
  1. Overall survival (OS)

    Defined as the time from start of study therapy to death due to any cause.

    Measured: Up to 5 years

  2. 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.

    Measured: Up to 5 years post treatment

  3. 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.

    Measured: Up to 5 years

  4. CNS-CE event free rate

    The 6-month CNS-CE rates from the Kaplan-Meier analysis will be compared between the arms.

    Measured: At 6 months

  5. 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.

    Measured: Baseline to 6 months post treatment

  6. 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.

    Measured: Up to 5 years post treatment

  7. Time to systemic therapy

    Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.

    Measured: Time to initiation or re-initiation of systemic therapy with pre-operative versus post-operative SRS, assessed up to 5 years

  8. Time to regional progression

    Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.

    Measured: Up to 5 years post treatment

  9. Time central nervous system (CNS) progression

    Will be estimated using the Kaplan-Meier method, and will be compared using log-rank tests.

    Measured: Up to 5 years post treatment

  10. 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.

    Measured: Up to 5 years

  11. 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.

    Measured: Up to 5 years post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2018
  2. Study start19 Nov 2018
  3. Primary completion8 Nov 2030 (estimated)
  4. Study completion8 Nov 2030 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
140 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03750227
Sponsor's protocol ID
MC167C
Other IDs
NCI-2018-02799, 17-007708, MC167C
Status last verified
Aug 2026
First submitted
20 Nov 2018
Last updated
19 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Routman DM, Jusue-Torres I, Brown PD, Trifiletti DM, Vora SA, Brown DA, Parney IF, Burns TC, Yan E. Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial. BMC Cancer. 2024 Mar 12;24(1):332. doi: 10.1186/s12885-024-12060-9.

    PubMed 38475765

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Conventional Surgery, Questionnaire Administration and Stereotactic Radiosurgery in people with Malignant Solid Neoplasm and Metastatic Malignant Neoplasm in the Brain, run by Mayo Clinic at 4 sites 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 7 inclusion and 18 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 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Clinical Trials Referral Office (855-776-0015, mayocliniccancerstudies@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Central nervous system (CNS) composite endpoint event (CNS-CE event) (time frame: Time from study randomization to documentation of the first CNS-CE event, assessed up to 5 years). 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 NCT03750227, 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 19 Aug 2026.

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