Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain

September 9, 2026 updated by: NRG Oncology

Phase III Trial of Single Fraction Stereotactic Radiosurgery (SRS) Versus Fractionated SRS (FSRS) for Intact Brain Metastases

This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if the time to local failure is improved with FSRS compared to SRS in patients with intact (i.e., unresected) brain metastases.

SECONDARY OBJECTIVES:

I. To compare time to intracranial progression-free survival between FSRS and SRS.

II. To compare overall survival between FSRS and SRS. III. To determine if the time to local failure is improved with FSRS compared to SRS, as evaluated by central review of imaging.

IV. To evaluate if there is any difference in central nervous system (CNS) failure patterns (local versus [vs.] distant brain failure vs. both) in patients who receive FSRS compared to patients who receive SRS.

V. To compare the rates of radiation necrosis in patients who receive FSRS vs. SRS.

VI. To compare the time to salvage whole brain radiation therapy (WBRT) between patients who receive FSRS and those who receive SRS.

VII. To compare the rates of post-treatment adverse events associated with FSRS and SRS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo SRS over 30-90 minutes for 1 fraction on study. Additionally, patients undergo computed tomography (CT) and magnetic resonance imaging (MRI) on study.

ARM II: Patients undergo FSRS over 30-90 minutes for 3 fractions on study. Additionally, patients undergo CT and MRI on study.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year then every 6 months for 3 years.

Study Type

Interventional

Enrollment (Actual)

274

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'Universite de Montreal
  • Hong Kong
      • Chai Wan, Hong Kong
        • Pamela Youde Nethersole Eastern Hospital
  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Cork, Ireland
        • Cork Radiation Oncology Associates Limited
    • Co Dublin
      • Dublin, Co Dublin, Ireland, 18
        • Beacon Hospital
      • Dublin, Co Dublin, Ireland, 6
        • Saint Lukes Hospital
    • Co Galway
      • Galway, Co Galway, Ireland
        • University College Hospital Galway
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • Arkansas
      • Fort Smith, Arkansas, United States, 72903
        • Mercy Hospital Fort Smith
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Anaheim, California, United States, 92806
        • Kaiser Permanente-Anaheim
      • Bellflower, California, United States, 90706
        • Kaiser Permanente-Bellflower
      • Corona, California, United States, 92882
        • City of Hope Corona
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Encinitas, California, United States, 92024
        • UC San Diego Health System - Encinitas
      • Irvine, California, United States, 92618
        • City of Hope at Irvine Lennar
      • Irvine, California, United States, 92612
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • Lancaster, California, United States, 93534
        • City of Hope Antelope Valley
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Napa, California, United States, 94558
        • Providence Queen of The Valley
      • Ontario, California, United States, 91761
        • Kaiser Permanente-Ontario
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • San Diego, California, United States, 92103
        • UC San Diego Medical Center - Hillcrest
      • Santa Rosa, California, United States, 95403
        • Providence Medical Foundation - Santa Rosa
      • South Pasadena, California, United States, 91030
        • City of Hope South Pasadena
      • Torrance, California, United States, 90503
        • City of Hope South Bay
      • Upland, California, United States, 91786
        • City of Hope Upland
      • Walnut Creek, California, United States, 94598
        • John Muir Medical Center-Walnut Creek
    • Colorado
      • Aurora, Colorado, United States, 80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs, Colorado, United States, 80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs, Colorado, United States, 80920
        • Memorial Hospital North
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Fort Collins, Colorado, United States, 80528
        • Cancer Care and Hematology-Fort Collins
      • Greeley, Colorado, United States, 80631
        • UCHealth Greeley Hospital
      • Loveland, Colorado, United States, 80538
        • Medical Center of the Rockies
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
      • New Britain, Connecticut, United States, 06050
        • The Hospital of Central Connecticut
    • Florida
      • Aventura, Florida, United States, 33180
        • UM Sylvester Comprehensive Cancer Center at Aventura
      • Boca Raton, Florida, United States, 33486
        • Boca Raton Regional Hospital
      • 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
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Miami, Florida, United States, 33176
        • Miami Cancer Institute
      • Miami, Florida, United States, 33176
        • UM Sylvester Comprehensive Cancer Center at Kendall
      • 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, 30309
        • Piedmont Hospital
      • Austell, Georgia, United States, 30106
        • WellStar Cobb Hospital
      • Marietta, Georgia, United States, 30060
        • Wellstar Kennestone Hospital
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • 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
        • 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
      • ‘Ewa Beach, Hawaii, United States, 96706
        • The Queen's Medical Center - West Oahu
    • Illinois
      • 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
      • Chicago, Illinois, United States, 60612
        • Rush MD Anderson Cancer Center
      • 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
      • 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
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • 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
      • O'Fallon, Illinois, United States, 62269
        • HSHS Saint Elizabeth's Hospital
      • Orland Park, Illinois, United States, 60462
        • University of Chicago Medicine-Orland Park
      • Orland Park, Illinois, United States, 60462
        • Northwestern Medicine Orland Park
      • Shiloh, Illinois, United States, 62269
        • Memorial Hospital East
      • 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
      • Crown Point, Indiana, United States, 46307
        • UChicago Medicine Northwest Indiana
      • Crown Point, Indiana, United States, 46307
        • Northwest Cancer Center - Crown Point
      • Dyer, Indiana, United States, 46311
        • Northwest Oncology LLC
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care
      • Hobart, Indiana, United States, 46342
        • Northwest Cancer Center - Hobart
      • Hobart, Indiana, United States, 46342
        • Saint Mary Medical Center
      • Munster, Indiana, United States, 46321
        • The Community Hospital
      • Munster, Indiana, United States, 46321
        • Women's Diagnostic Center - Munster
      • Valparaiso, Indiana, United States, 46383
        • Northwest Cancer Center - Valparaiso
    • Iowa
      • Ames, Iowa, United States, 50010
        • Mary Greeley Medical Center
      • Ames, Iowa, United States, 50010
        • McFarland Clinic - Ames
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Olathe, Kansas, United States, 66061
        • The University of Kansas Cancer Center - Olathe
      • Overland Park, Kansas, United States, 66210
        • University of Kansas Cancer Center-Overland Park
    • Kentucky
      • Elizabethtown, Kentucky, United States, 42701
        • Baptist Health Hardin
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • The James Graham Brown Cancer Center at University of Louisville
      • Louisville, Kentucky, United States, 40241
        • Norton Brownsboro Hospital and Medical Campus
      • Louisville, Kentucky, United States, 40245
        • UofL Health Medical Center Northeast
      • Owensboro, Kentucky, United States, 42303
        • Owensboro Health Mitchell Memorial Cancer Center
    • Maine
      • Portland, Maine, United States, 04102
        • MaineHealth Maine Medical Center - Portland
      • Sanford, Maine, United States, 04073
        • MaineHealth Cancer Care Center of York County
      • Scarborough, Maine, United States, 04074
        • MaineHealth Maine Medical Center- Scarborough
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
      • Baltimore, Maryland, United States, 21201
        • Maryland Proton Treatment Center
      • Bel Air, Maryland, United States, 21014
        • UM Upper Chesapeake Medical Center
      • Columbia, Maryland, United States, 21044
        • Central Maryland Radiation Oncology in Howard County
      • Easton, Maryland, United States, 21601
        • University of Maryland Shore Medical Center at Easton
      • Glen Burnie, Maryland, United States, 21061
        • UM Baltimore Washington Medical Center/Tate Cancer Center
      • Largo, Maryland, United States, 20774
        • UM Capital Region Medical Center
      • Westminster, Maryland, United States, 21157
        • William E Kahlert Regional Cancer Center/Sinai Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Rogel Cancer Center
      • Ann Arbor, Michigan, United States, 48106
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
      • Brighton, Michigan, United States, 48114
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
      • Brownstown, Michigan, United States, 48183
        • Henry Ford Cancer Institute-Downriver
      • Clinton Township, Michigan, United States, 48038
        • Henry Ford Macomb Hospital-Clinton Township
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Livonia, Michigan, United States, 48154
        • Trinity Health Saint Mary Mercy Livonia Hospital
      • Novi, Michigan, United States, 48374
        • Henry Ford Health Providence Novi Hospital
      • Saginaw, Michigan, United States, 48601
        • MyMichigan Medical Center Saginaw
      • Tawas City, Michigan, United States, 48764
        • MyMichigan Medical Center Tawas
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford West Bloomfield Hospital
      • Ypsilanti, Michigan, United States, 48197
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Minnesota
      • Chaska, Minnesota, United States, 55318
        • Minnesota Oncology Hematology PA-Chaska
      • Maple Grove, Minnesota, United States, 55369
        • Fairview Clinics and Surgery Center Maple Grove
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
      • Monticello, Minnesota, United States, 55362
        • Monticello Cancer Center
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Waconia, Minnesota, United States, 55387
        • Ridgeview Medical Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • City of Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
      • Columbia, Missouri, United States, 65212
        • MU Health - University Hospital/Ellis Fischel Cancer Center
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • Farmington, Missouri, United States, 63640
        • Parkland Health Center - Farmington
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63129
        • Siteman Cancer Center-South County
      • St Louis, Missouri, United States, 63136
        • Siteman Cancer Center at Christian Hospital
    • Nebraska
      • Bellevue, Nebraska, United States, 68123
        • Nebraska Medicine-Bellevue
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
      • Omaha, Nebraska, United States, 68118
        • Nebraska Medicine-Village Pointe
    • Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Cherry Hill, New Jersey, United States, 08002
        • Jefferson Cherry Hill Hospital
      • Livingston, New Jersey, United States, 07039
        • Saint Barnabas Medical Center
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
      • Neptune City, New Jersey, United States, 07753
        • Jersey Shore Medical Center
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
      • Newark, New Jersey, United States, 07101
        • Rutgers New Jersey Medical School
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paramus, New Jersey, United States, 07652
        • The Valley Hospital - Luckow Pavilion
      • Ridgewood, New Jersey, United States, 07450
        • Valley Health System Ridgewood Campus
      • Sewell, New Jersey, United States, 08080
        • Sidney Kimmel Cancer Center Washington Township
      • Somerville, New Jersey, United States, 08876
        • Robert Wood Johnson University Hospital Somerset
      • Toms River, New Jersey, United States, 08755
        • Community Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
    • New York
      • Brooklyn, New York, United States, 11215
        • New York-Presbyterian/Brooklyn Methodist Hospital
      • Brooklyn, New York, United States, 11220
        • NYU Langone Hospital - Brooklyn
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack
      • Flushing, New York, United States, 11355
        • The New York Hospital Medical Center of Queens
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • Mineola, New York, United States, 11501
        • NYU Langone Hospital - Long Island
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • 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, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10011
        • Mount Sinai Chelsea
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • New York, New York, United States, 10075
        • Lenox Hill Hospital
      • New York, New York, United States, 10065
        • Manhattan Eye Ear and Throat Hospital
      • Oceanside, New York, United States, 11572
        • Mount Sinai South Nassau
      • 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
      • Syracuse, New York, United States, 13215
        • SUNY Upstate Medical Center-Community Campus
      • 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
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Avon, Ohio, United States, 44011
        • UH Seidman Cancer Center at UH Avon Health Center
      • Beavercreek, Ohio, United States, 45431
        • Indu and Raj Soin Medical Center
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC 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
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
      • Youngstown, Ohio, United States, 44501
        • Saint Elizabeth Youngstown Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Clackamas, Oregon, United States, 97015
        • Clackamas Radiation Oncology Center
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
      • Tualatin, Oregon, United States, 97062
        • Legacy Meridian Park Hospital
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18104
        • Saint Luke's Cancer Center - Allentown
      • Bethlehem, Pennsylvania, United States, 18015
        • Saint Luke's University Hospital-Bethlehem Campus
      • Chambersburg, Pennsylvania, United States, 17201
        • Chambersburg Hospital
      • Dunmore, Pennsylvania, United States, 18512
        • Northeast Radiation Oncology Center
      • Easton, Pennsylvania, United States, 18045
        • Saint Luke's Hospital-Anderson Campus
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19114
        • Jefferson Torresdale Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania/Abramson Cancer Center
      • Philadelphia, Pennsylvania, United States, 19103
        • NRG Oncology
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC-Shadyside Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC-Presbyterian Hospital
      • Quakertown, Pennsylvania, United States, 18951
        • Saint Luke's Hospital - Upper Bucks Campus
      • Stroudsburg, Pennsylvania, United States, 18360
        • Saint Luke's Hospital - Monroe Campus
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Cancer Center
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Hospital
    • South Carolina
      • Greenville, South Carolina, United States, 29607
        • Saint Francis Cancer Center
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
    • 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, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37204
        • Vanderbilt Breast Center at One Hundred Oaks
    • Texas
      • Conroe, Texas, United States, 77384
        • MD Anderson in The Woodlands
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Houston, Texas, United States, 77030
        • Memorial Hermann Texas Medical Center
      • Houston, Texas, United States, 77079
        • MD Anderson West Houston
      • League City, Texas, United States, 77573
        • UT MD Anderson - League City
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • Sugar Land, Texas, United States, 77478
        • MD Anderson in Sugar Land
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
      • Burlington, Vermont, United States, 05405
        • University of Vermont and State Agricultural College
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
    • Washington
      • Renton, Washington, United States, 98055
        • Valley Medical Center
      • Vancouver, Washington, United States, 98686
        • Legacy Salmon Creek Hospital
      • Vancouver, Washington, United States, 98684
        • Legacy Cancer Institute Medical Oncology and Day Treatment
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • 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
      • Rhinelander, Wisconsin, United States, 54501
        • Aspirus Cancer Care - James Beck Cancer Center
      • Stevens Point, Wisconsin, United States, 54481
        • Aspirus Cancer Care - Stevens Point
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer 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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:

    • Non-small cell lung cancer
    • Melanoma
    • Breast cancer
    • Renal cell carcinoma
    • Gastrointestinal cancer
    • If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest/abdomen/pelvis, positron emission tomography [PET]/CT, etc.) is required
  • Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration
  • At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm

  • All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension

    • Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS/FSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator
  • Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5
  • No more than 2 lesions planned for resection if clinically indicated

  • No known 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
  • Age ≥ 18 years
  • Karnofsky performance status (KPS) ≥ 60
  • 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
  • No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation [PCI])
  • New York Heart Association Functional Classification II or better (NYHA Functional Classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
  • No active infection currently requiring intravenous (IV) antibiotic management
  • No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy

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 (SRS)
Patients undergo SRS over 30-90 minutes for 1 fraction on study. Additionally, patients undergo CT and MRI on study.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Radiation: Stereotactic Radiosurgery
Undergo SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
  • Stereotactic Radiation Therapy
  • SRS
Experimental: ARM II (FSRS)
Patients undergo FSRS over 30-90 minutes for 3 fractions on study. Additionally, patients undergo CT and MRI on study.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Radiation: Fractionated Stereotactic Radiation Therapy
Undergo FSRS
Other Names:
  • Fractionated Stereotactic Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to local failure
Time Frame: From randomization (with the treatment planning magnetic resonance imaging as the 'baseline' for purposes of disease assessment) to local tumor progression of any study lesion(s), assessed up to 5 years
The time to local failure will be evaluated at a per-patient level. The cause-specific hazard ratio will be estimated in a Cox proportional hazards (PH) model adjusting for patients and disease characteristics. The Cox PH model will be the principle approach. The cumulative incidence function estimator will also be used to estimate the rate of local failure in the presence of competing event of deaths in the two arms separately. A complementary analysis will involve Gray's test to evaluate the difference in the distribution of local failure between treatment arms. These results will be interpreted in light of the competing deaths.
From randomization (with the treatment planning magnetic resonance imaging as the 'baseline' for purposes of disease assessment) to local tumor progression of any study lesion(s), assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial progression-free survival (IPFS)
Time Frame: From the date of randomization until intracranial progression (local or distant intracranial) or death from any cause, whichever occurs first, assessed up to 5 years
IPFS will consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a stratified log-rank test. Statistical power will depend on the total IPFS events accumulated at trial end.
From the date of randomization until intracranial progression (local or distant intracranial) or death from any cause, whichever occurs first, assessed up to 5 years
Overall survival
Time Frame: From the date of randomization until death from any cause, assessed up to 5 years
Will consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a stratified log-rank test. Reasons for death (e.g. due to neurological cause [any central nervous system event such as an intracranial mass, hemorrhage, or hydrocephalus] or non-neurological cause) will be recorded.
From the date of randomization until death from any cause, assessed up to 5 years
Time to radiation necrosis (TTRN)
Time Frame: From randomization until radiation necrosis, assessed up to 5 years
The rate of radiation necrosis will be compared in patients who receive fractionated stereotactic radiosurgery to patients who receive stereotactic radiosurgery. The primary comparison of treatment effect on TTRN will be based on testing the cause-specific hazard ratio (CHR) in a univariate Cox proportional hazards model. Additional supplementary analyses will include estimating the cause specific ratio in a Cox proportional hazards model adjusting for patients and disease characteristics (e.g. stratification randomization factors) and estimating the median TTRN via the cumulative incidence function estimator (Korn 1992). The Gray's test will also be used to evaluate the difference in the distribution of TTRN between treatment arms (Gray 1988).
From randomization until radiation necrosis, assessed up to 5 years
Time to whole brain radiation therapy (WBRT)
Time Frame: Up to 5 years
Analysis of time to WBRT will consist of estimation of its distribution for each treatment arm via the Kaplan-Meier method and a stratified log-rank test. For patients who die prior to WBRT, time to WBRT will be censored at time of death.
Up to 5 years
Incidence of adverse events (AEs)
Time Frame: Up to 2 years from start of radiation treatment
AEs will be graded according to Common Terminology Criteria in Adverse Events version 5.0. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst AE per patients 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 arms. Frequencies for specific potentially treatment related AEs where grade 3 or higher events are noted may be compared. Any frequencies to be tested will be evaluated using the chi-square or exact test as appropriate, with two-sided significance level of 0.05.
Up to 2 years from start of radiation treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to local failure
Time Frame: Up to 5 years
Estimates of the primary outcome treatment effect and the corresponding 95% confidence interval will be provided by sex, race, and ethnicity.
Up to 5 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: Rupesh R Kotecha, NRG Oncology

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)

December 12, 2024

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

June 30, 2033

Study Registration Dates

First Submitted

July 8, 2024

First Submitted That Met QC Criteria

July 8, 2024

First Posted (Actual)

July 15, 2024

Study Record Updates

Last Update Posted (Actual)

September 14, 2026

Last Update Submitted That Met QC Criteria

September 9, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NRG-BN013 (Other Identifier: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NCI-2024-04812 (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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