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

NCT ID: NCT03750227

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-19

Study Completion Date

2030-11-08

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Malignant Solid Neoplasm Metastatic Malignant Neoplasm in the Brain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (Post-operative SRS)

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.

Group Type ACTIVE_COMPARATOR

Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Stereotactic Radiosurgery

Intervention Type RADIATION

Undergo stereotactic radiosurgery

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample, tissue and CSF sample collection

Arm B (Pre-operative SRS)

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.

Group Type EXPERIMENTAL

Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Stereotactic Radiosurgery

Intervention Type RADIATION

Undergo stereotactic radiosurgery

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample, tissue and CSF sample collection

Interventions

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Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Stereotactic Radiosurgery

Undergo stereotactic radiosurgery

Intervention Type RADIATION

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample, tissue and CSF sample collection

Intervention Type PROCEDURE

Other Intervention Names

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Stereotactic External Beam Irradiation stereotactic external-beam radiation therapy Stereotactic Radiation Therapy Stereotactic Radiotherapy stereotaxic radiation therapy stereotaxic radiosurgery SRS CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan Medical Imaging Magnetic Resonance / Nuclear Magnetic Resonance MR MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging Structural MRI sMRI Biological Sample Collection Specimen Collection

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elizabeth Yan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status RECRUITING

National Institutes of Neurological Disorders and Stroke, NIH

Bethesda, Maryland, United States

Site Status RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Trials Referral Office

Role: CONTACT

Phone: 855-776-0015

Email: [email protected]

Facility Contacts

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Clinical Trials Referral Office

Role: primary

Clinical Trials Referral Office

Role: primary

DeeDee K. Brown, M.D., Ph.D.

Role: primary

Clinical Trials Referral Office

Role: primary

References

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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.

Reference Type DERIVED
PMID: 38475765 (View on PubMed)

Related Links

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Other Identifiers

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NCI-2018-02799

Identifier Type: REGISTRY

Identifier Source: secondary_id

17-007708

Identifier Type: OTHER

Identifier Source: secondary_id

MC167C

Identifier Type: OTHER

Identifier Source: secondary_id

MC167C

Identifier Type: -

Identifier Source: org_study_id