Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases

May 18, 2026 updated by: NRG Oncology

A Randomized Phase III Trial of Pre-Operative Compared to Post-Operative Stereotactic Radiosurgery in Patients With Resectable Brain Metastases

This phase III trial compares the usual treatment of surgery after stereotactic radiosurgery (SRS) to receiving SRS before surgery in treating patients with cancer that has spread to the brain (brain metastases). Stereotactic radiosurgery is a type of radiation therapy that delivers a high dose of radiation to target tumors and minimizes effect on normal surrounding brain tissue. The combination of surgery and radiation may stop the tumor from growing for a few months or longer and may reduce symptoms of brain metastases. This study investigates whether treating with SRS before surgery may be better than SRS after surgery in reducing the possibility of the tumor coming back, reducing or preventing the cancer from spreading to other areas of the brain and reducing the risk of scarring on the brain from radiation.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if the time to composite adverse endpoint (CAE) (defined as: 1) local tumor progression within the surgical bed; and/or 2) adverse radiation effect [ARE], the imaging correlate of post-stereotactic radiosurgery [SRS] radiation necrosis; and/or 3) nodular meningeal disease [nMD]) is improved in patients treated with pre-resection SRS to the intact lesion versus those treated with post-resection SRS.

SECONDARY OBJECTIVES:

I. To assess the trajectory of symptom burden in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by MD Anderson Symptom Inventory for brain tumor (MDASI-BT).

II. To determine whether there is improved overall survival (OS) in patients with resected brain metastases who undergo pre-resection SRS compared to patients who receive post-resection SRS.

III. To compare rates of ARE, the imaging correlate of radiation necrosis, in patients who receive pre-resection SRS to patients who receive post-resection SRS.

IV. To determine whether there is increased time to whole brain radiotherapy (WBRT) in patients who receive pre-resection SRS compared to patients who receive post-resection SRS.

V. To assess the trajectory of neuro-cognitive function in patients treated with pre-resection SRS to the intact lesion versus those treated to the post-resection surgical cavity as measured by the Montreal Cognitive Assessment (MoCA).

VI. To compare rates of nodular meningeal disease in patients who receive pre-resection SRS to patients who receive post-resection SRS.

VII. To compare rates of local recurrence in the resection cavity for patients who receive pre-resection SRS to patients who receive post-resection SRS.

VIII. To compare rates of local recurrence of intact, non-index metastases treated with SRS.

IX. To compare rates of distant brain failure in patients who receive pre-resection SRS to patients who receive post-resection SRS.

X. To assess toxicity in the two treatment arms.

EXPLORATORY OBJECTIVE:

I. To explore if the type of surgical resection (piece-meal versus [vs.] en-bloc) may be associated with the rate of nodular meningeal disease.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction.

ARM II: Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for additional 2 years.

Study Type

Interventional

Enrollment (Actual)

237

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3H 2R9
        • The Research Institute of the McGill University Health Centre (MUHC)
      • Montreal, Quebec, Canada, H2X 3E4
        • CHUM - Centre Hospitalier de l'Université de Montréal
      • Québec, Quebec, Canada, G1R 2J6
        • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
  • Japan
      • Kyoto, Japan, 606-8507
        • Kyoto University Hospital
      • Showa-Ku Nagoya, Japan, 466-0065
        • Nagoya University Hospital
      • Tokyo, Japan, 104 0045
        • National Cancer Center Hospital
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8648
        • Hokkaido University Hospital
    • Maebashi
      • Gunma, Maebashi, Japan, 371-8511
        • Gunma University Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Saint Joseph's Hospital and Medical Center
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • California
      • Anaheim, California, United States, 92806
        • Kaiser Permanente-Anaheim
      • Auburn, California, United States, 95602
        • Sutter Auburn Faith Hospital
      • Auburn, California, United States, 95603
        • Sutter Cancer Centers Radiation Oncology Services-Auburn
      • Bellflower, California, United States, 90706
        • Kaiser Permanente-Bellflower
      • Irvine, California, United States, 92612
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Modesto, California, United States, 95355
        • Memorial Medical Center
      • Ontario, California, United States, 91761
        • Kaiser Permanente-Ontario
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Orange, California, United States, 92868
        • Saint Joseph Hospital - Orange
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Roseville, California, United States, 95661
        • Sutter Cancer Centers Radiation Oncology Services-Roseville
      • Roseville, California, United States, 95661
        • Sutter Roseville Medical Center
      • Sacramento, California, United States, 95816
        • Sutter Medical Center Sacramento
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center-Pacific Campus
      • San Francisco, California, United States, 94143
        • UCSF Medical Center-Parnassus
      • Santa Rosa, California, United States, 95403
        • Sutter Pacific Medical Foundation
      • Vallejo, California, United States, 94589
        • Sutter Solano Medical Center/Cancer Center
    • Florida
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Doral, Florida, United States, 33166
        • UM Sylvester Comprehensive Cancer Center at Doral
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic in Florida
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Plantation, Florida, United States, 33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
      • Tampa, Florida, United States, 33607
        • Moffitt Cancer Center-International Plaza
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center - McKinley Campus
      • Wesley Chapel, Florida, United States, 33544
        • Moffitt Cancer Center at Wesley Chapel
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Emory Saint Joseph's Hospital
      • Atlanta, Georgia, United States, 30303
        • Grady Health System
      • Atlanta, Georgia, United States, 30309
        • Piedmont Hospital
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
      • Honolulu, Hawaii, United States, 96813
        • Hawaii Cancer Care Inc - Waterfront Plaza
      • Honolulu, Hawaii, United States, 96813
        • Queen's Cancer Cenrer - POB I
      • Honolulu, Hawaii, United States, 96813
        • Straub Clinic and Hospital
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii Cancer Center
      • Honolulu, Hawaii, United States, 96817
        • Queen's Cancer Center - Kuakini
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
      • Kailua, Hawaii, United States, 96734
        • Castle Medical Center
      • Lihue, Hawaii, United States, 96766
        • Wilcox Memorial Hospital and Kauai Medical Clinic
      • ‘Aiea, Hawaii, United States, 96701
        • Hawaii Cancer Care - Westridge
      • ‘Aiea, Hawaii, United States, 96701
        • Pali Momi Medical Center
      • ‘Ewa Beach, Hawaii, United States, 96706
        • The Queen's Medical Center - West Oahu
    • Illinois
      • Aurora, Illinois, United States, 60506
        • Advocate Outpatient Center - Aurora
      • Barrington, Illinois, United States, 60010
        • Advocate Good Shepherd Hospital
      • Centralia, Illinois, United States, 62801
        • Centralia Oncology Clinic
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Crystal Lake, Illinois, United States, 60014
        • AMG Crystal Lake - Oncology
      • Danville, Illinois, United States, 61832
        • Carle at The Riverfront
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois - Decatur
      • Downers Grove, Illinois, United States, 60515
        • Advocate Good Samaritan Hospital
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Effingham, Illinois, United States, 62401
        • Carle Physician Group-Effingham
      • Elmhurst, Illinois, United States, 60126
        • Elmhurst Memorial Hospital
      • Hazel Crest, Illinois, United States, 60429
        • Advocate South Suburban Hospital
      • Libertyville, Illinois, United States, 60048
        • AMG Libertyville - Oncology
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • Naperville, Illinois, United States, 60540
        • Edward Hospital/Cancer Center
      • New Lenox, Illinois, United States, 60451
        • UC Comprehensive Cancer Center at Silver Cross
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • Oak Lawn, Illinois, United States, 60453-2699
        • Advocate Christ Medical Center
      • Park Ridge, Illinois, United States, 60068
        • Advocate Lutheran General Hospital
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • Springfield, Illinois, United States, 62781
        • Springfield Memorial Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Ascension Saint Vincent Indianapolis Hospital
    • Iowa
      • Ankeny, Iowa, United States, 50023
        • UI Health Care Mission Cancer and Blood - Ankeny Clinic
      • Clive, Iowa, United States, 50325
        • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50309
        • UI Health Care Mission Cancer and Blood - Des Moines Clinic
      • Des Moines, Iowa, United States, 50314
        • UI Health Care Mission Cancer and Blood - Laurel Clinic
      • Waukee, Iowa, United States, 50263
        • UI Health Care Mission Cancer and Blood - Waukee Clinic
    • Kentucky
      • Louisville, Kentucky, United States, 40241
        • Norton Brownsboro Hospital and Medical Campus
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Bel Air, Maryland, United States, 21014
        • UM Upper Chesapeake Medical Center
      • Glen Burnie, Maryland, United States, 21061
        • UM Baltimore Washington Medical Center/Tate Cancer Center
      • Largo, Maryland, United States, 20774
        • UM Capital Region Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Rogel Cancer Center
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Royal Oak, Michigan, United States, 48073
        • Corewell Health William Beaumont University Hospital
      • Troy, Michigan, United States, 48085
        • Corewell Health Beaumont Troy Hospital
    • Minnesota
      • Brainerd, Minnesota, United States, 56401
        • Essentia Health Saint Joseph's Medical Center
      • Deer River, Minnesota, United States, 56636
        • Essentia Health - Deer River Clinic
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Cancer Center
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Saint Mary's Medical Center
      • Duluth, Minnesota, United States, 55805
        • Miller-Dwan Hospital
      • Hibbing, Minnesota, United States, 55746
        • Essentia Health Hibbing Clinic
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Sandstone, Minnesota, United States, 55072
        • Essentia Health Sandstone
      • Virginia, Minnesota, United States, 55792
        • Essentia Health Virginia Clinic
    • Missouri
      • Farmington, Missouri, United States, 63640
        • Parkland Health Center - Farmington
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
      • Sainte Genevieve, Missouri, United States, 63670
        • Sainte Genevieve County Memorial Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
      • St Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Sullivan, Missouri, United States, 63080
        • Missouri Baptist Sullivan Hospital
      • Sunset Hills, Missouri, United States, 63127
        • BJC Outpatient Center at Sunset Hills
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Great Falls, Montana, United States, 59405
        • Benefis Sletten Cancer Institute
    • Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper Hospital University Medical Center
      • Jersey City, New Jersey, United States, 07302
        • Jersey City Medical Center
      • Livingston, New Jersey, United States, 07039
        • Saint Barnabas Medical Center
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paramus, New Jersey, United States, 07652
        • The Valley Hospital - Luckow Pavilion
      • Pennington, New Jersey, United States, 08534
        • Capital Health Medical Center-Hopewell
      • Ridgewood, New Jersey, United States, 07450
        • Valley Health System Ridgewood Campus
      • Toms River, New Jersey, United States, 08755
        • Community Medical Center
      • Westwood, New Jersey, United States, 07675
        • Valley Health System-Hematology/Oncology
    • New York
      • Brooklyn, New York, United States, 11215
        • New York-Presbyterian/Brooklyn Methodist Hospital
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Flushing, New York, United States, 11355
        • The New York Hospital Medical Center of Queens
      • Mount Kisco, New York, United States, 10549
        • Northern Westchester Hospital
      • New York, New York, United States, 10019
        • Mount Sinai West
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10011
        • Mount Sinai Chelsea
      • New York, New York, United States, 10075
        • Lenox Hill Hospital
      • New York, New York, United States, 10065
        • Manhattan Eye Ear and Throat Hospital
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
      • West Islip, New York, United States, 11795
        • Good Samaritan University Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Concord, North Carolina, United States, 28025
        • Atrium Health Cabarrus/LCI-Concord
      • Gastonia, North Carolina, United States, 28054
        • CaroMont Regional Medical Center
      • Wilmington, North Carolina, United States, 28401
        • Novant Health Cancer Institute Radiation Oncology - Wilmington
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Beavercreek, Ohio, United States, 45431
        • Indu and Raj Soin Medical Center
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43215
        • Grant Medical Center
      • Delaware, Ohio, United States, 43015
        • Delaware Health Center-Grady Cancer Center
      • Delaware, Ohio, United States, 43015
        • Grady Memorial Hospital
      • Kettering, Ohio, United States, 45429
        • Kettering Medical Center
      • Perrysburg, Ohio, United States, 43551
        • Mercy Health - Perrysburg Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Dunmore, Pennsylvania, United States, 18512
        • Northeast Radiation Oncology Center
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC-Shadyside Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC-Presbyterian Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Gaffney, South Carolina, United States, 29341
        • Gibbs Cancer Center-Gaffney
      • Greer, South Carolina, United States, 29651
        • Gibbs Cancer Center-Pelham
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
      • Union, South Carolina, United States, 29379
        • SMC Center for Hematology Oncology Union
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • The Children's Hospital at TriStar Centennial
    • Texas
      • Lubbock, Texas, United States, 79410
        • Covenant Medical Center-Lakeside
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Richmond, Virginia, United States, 23229
        • Henrico Doctor's Hospital
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
      • Richmond, Virginia, United States, 23235
        • CJW Medical Center - Johnston-Willis Campus
      • Roanoke, Virginia, United States, 24033
        • Carilion Roanoke Memorial Hospital
    • Washington
      • Seattle, Washington, United States, 98122-5711
        • Swedish Medical Center-Cherry Hill
    • Wisconsin
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center
      • Ashland, Wisconsin, United States, 54806
        • Duluth Clinic Ashland
      • Ashland, Wisconsin, United States, 54806
        • Northwest Wisconsin Cancer Center
      • Burlington, Wisconsin, United States, 53105
        • Aurora Cancer Care-Southern Lakes VLCC
      • Germantown, Wisconsin, United States, 53022
        • Aurora Health Care Germantown Health Center
      • Grafton, Wisconsin, United States, 53024
        • Aurora Cancer Care-Grafton
      • Green Bay, Wisconsin, United States, 54311
        • Aurora BayCare Medical Center
      • Hayward, Wisconsin, United States, 54843
        • Essentia Health-Hayward Clinic
      • Johnson Creek, Wisconsin, United States, 53038
        • University of Wisconsin Carbone Cancer Center - Johnson Creek
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Madison, Wisconsin, United States, 53718
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Milwaukee, Wisconsin, United States, 53209
        • Aurora Cancer Care-Milwaukee
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Saint Luke's Medical Center
      • Milwaukee, Wisconsin, United States, 53233
        • Aurora Sinai Medical Center
      • Oshkosh, Wisconsin, United States, 54904
        • Vince Lombardi Cancer Clinic - Oshkosh
      • Racine, Wisconsin, United States, 53406
        • Aurora Cancer Care-Racine
      • Rhinelander, Wisconsin, United States, 54501
        • Aspirus Cancer Care - James Beck Cancer Center
      • Sheboygan, Wisconsin, United States, 53081
        • Vince Lombardi Cancer Clinic-Sheboygan
      • Spooner, Wisconsin, United States, 54801
        • Essentia Health-Spooner Clinic
      • Stevens Point, Wisconsin, United States, 54481
        • Aspirus Cancer Care - Stevens Point
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Superior, Wisconsin, United States, 54880
        • Essentia Health Saint Mary's Hospital - Superior
      • Waukesha, Wisconsin, United States, 53188
        • UW Cancer Center at ProHealth Care
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer Center
      • Wauwatosa, Wisconsin, United States, 53226
        • Aurora Cancer Care-Milwaukee West
      • West Allis, Wisconsin, United States, 53227
        • Aurora West Allis Medical Center
      • Wisconsin Rapids, Wisconsin, United States, 54494
        • Aspirus Cancer Care - Wisconsin Rapids

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Radiographic confirmation of 1-4 brain metastases, one of which requires resection, as defined by magnetic resonance imaging (MRI) with contrast obtained within 14 days prior to registration

    • The maximum diameter of the lesion to be resected on the post-contrast MRI, as measured on any orthogonal plane (axial, sagittal, coronal), must measure >= 2.0 cm and =< 5.0 cm.
    • The maximum diameter of any lesions which will not be resected must be =< 4.0 cm in maximum diameter
  • Known active or history of invasive non-central nervous system (CNS) primary cancer based on documented pathologic diagnosis within the past 3 years
  • All brain metastases must be located >= 5 mm from the optic chiasm and outside the brainstem
  • Patient is able to medically tolerate surgery and SRS
  • Lesions chosen for surgical therapy must be deemed appropriate targets for safe, gross total resection by the treating surgeon
  • History/physical examination within 14 days prior to registration
  • Age >= 18
  • Karnofsky performance status (KPS) >= 60 within 14 days prior to registration
  • A negative urine or serum pregnancy test (in persons of childbearing potential) within =< 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
  • Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment on this study to prevent pregnancy
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

  • Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to the resection site

    • Note: The index lesion to be resected cannot have been previously treated with SRS (i.e. repeat radiosurgery to the same location/lesion is not allowed on this protocol). Previous SRS to other lesions is allowed

  • Evidence of leptomeningeal disease (LMD)

    • Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion
  • Any medical conditions which would make this protocol unreasonably hazardous, including, but not limited to: contraindications to general endotracheal anesthesia; intracranial surgery; and stereotactic radiosurgery
  • Primary histology of germ cell tumor, small cell carcinoma or lymphoma
  • More than one brain metastasis planned for resection
  • Inability to undergo MRI with contrast

  • Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors within the 3 days prior to, the day of, or within 3 days after the completion of SRS

    • Note: chemotherapy and immunotherapy outside of this window are allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I (surgery, stereotactic radiosurgery)
Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Radiation: Stereotactic Radiosurgery
Undergo stereotactic radiosurgery
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
  • SRS
Procedure: Brain Surgery
Undergo surgery per standard of care
Experimental: Arm II (stereotactic radiosurgery, surgery)
Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Radiation: Stereotactic Radiosurgery
Undergo stereotactic radiosurgery
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
  • SRS
Procedure: Brain Surgery
Undergo surgery per standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to composite adverse endpoint (CAE)
Time Frame: Time from surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment) to local tumor progression (within the surgical bed), nodular meningeal disease, or radiation necrosis, whichever occurs first, assessed up to 4 years
Analysis for this endpoint will consist of testing the cause-specific hazard ratio in a Cox proportional hazards model.
Time from surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment) to local tumor progression (within the surgical bed), nodular meningeal disease, or radiation necrosis, whichever occurs first, assessed up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of adverse events (AEs)
Time Frame: Up to 4 years
AEs will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. The proportion of patients with at least one grade 3 or higher AE will be compared between treatment arms. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level 0.05.
Up to 4 years
Change in MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Time Frame: Baseline up to 2 years after surgery
Will implement mixed effects models for repeated measures to evaluate the MDASI-BT scores longitudinally.
Baseline up to 2 years after surgery
Change in cognitive function
Time Frame: Baseline up to 2 years after surgery
Measured by Montreal Cognitive Assessment (MoCA). Will implement mixed effects models for repeated measures to evaluate the MoCA scores longitudinally.
Baseline up to 2 years after surgery
Overall survival (OS)
Time Frame: Time from randomization to death due to any cause, assessed up to 4 years
Analysis for this endpoint will consist of estimation of the OS distribution of each treatment arm via the Kaplan-Meier method and a stratified log-rank test.
Time from randomization to death due to any cause, assessed up to 4 years
Rate of local tumor progression
Time Frame: Up to 4 years
The time origin for these imaging-based endpoints will be time of surgery (with the post-operative magnetic resonance imaging [MRI] as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of local progression between treatment arms.
Up to 4 years
Rate of radiation necrosis
Time Frame: Up to 4 years
The time origin for these imaging-based endpoints will be time of surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of radiation necrosis between treatment arms.
Up to 4 years
Rate of nodular meningeal disease
Time Frame: Up to 4 years
The time origin for these imaging-based endpoints will be time of surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of nodular meningeal disease between treatment arms.
Up to 4 years
Rate of distant brain failures
Time Frame: Up to 4 years
The time origin for these imaging-based endpoints will be time of surgery (with the post-operative MRI as the 'baseline' for purposes of disease assessment). These analyses will involve estimating the cumulative incidence function of local progression, radiation necrosis, nodular meningeal disease, and distant brain failures in the presence of competing event of deaths. The Gray's test will be used to evaluate the difference in the distribution of distant brain failures between treatment arms.
Up to 4 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Type of surgical resection
Time Frame: Up to 4 years
Will compare if the type of surgical resection (piece-meal vs. en-bloc) may be associated with the rate of nodular meningeal disease. The competing risk approach by Gray (Gray 1988) will be used to compare the cumulative incidences of nMD by surgical type, where death prior to nMD will be treated as a competing risk event. This analysis will only include patients who undergo surgical resections at baseline.
Up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NRG Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Stuart H Burri, NRG Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 24, 2022

Primary Completion (Estimated)

March 16, 2027

Study Completion (Estimated)

March 16, 2027

Study Registration Dates

First Submitted

June 24, 2022

First Submitted That Met QC Criteria

June 24, 2022

First Posted (Actual)

June 29, 2022

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-BN012 (Other Identifier: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NCI-2022-04804 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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