Testing Whether Treating Breast Cancer Metastases With Surgery or High-Dose Radiation Improves Survival
A Phase IIR/III Trial of Standard of Care Therapy With or Without Stereotactic Body Radiotherapy (SBRT) and/or Surgical Ablation for Newly Oligometastatic Breast Cancer
3 other identifiers
interventional
129
4 countries
162
Brief Summary
This randomized phase II/III trial studies how well standard of care therapy with stereotactic radiosurgery and/or surgery works and compares it to standard of care therapy alone in treating patients with breast cancer that has spread to one or two locations in the body (limited metastatic) that are previously untreated. Standard of care therapy comprising chemotherapy, hormonal therapy, biological therapy, and others may help stop the spread of tumor cells. Radiation therapy and/or surgery is usually only given with standard of care therapy to relieve pain; however, in patients with limited metastatic breast cancer, stereotactic radiosurgery, also known as stereotactic body radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue and surgery may be able to effectively remove the metastatic tumor cells. It is not yet known whether standard of care therapy is more effective with stereotactic radiosurgery and/or surgery in treating limited metastatic breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2014
Longer than P75 for phase_2
162 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 24, 2014
CompletedFirst Submitted
Initial submission to the registry
February 5, 2015
CompletedFirst Posted
Study publicly available on registry
February 18, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 20, 2021
CompletedResults Posted
Study results publicly available
February 8, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 4, 2025
CompletedApril 24, 2026
April 1, 2026
7 years
February 5, 2015
December 14, 2022
April 7, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Progression-free Survival (Phase II)
Progression (failure) is defined as any of the following: progression of metastases, new metastases, or death. Progression-free survival (PFS) time is defined as time from randomization to the date of first progression, death, or last contact when participant had a documented clinical assessment (censored). PFS rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Median PFS is provided.
From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months, then every six months to five years, then annually. Maximum follow-up at time of analysis was 63 months.
Overall Survival (Phase III)
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored).
From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months and then annually. Maximum follow-up at time of analysis was 63 months.
Secondary Outcomes (4)
Percentage of Participants With Treated Metastasis Progression on the SOC + Ablation Arm
From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months. Two-year rates are provide here.
Percentage of Participants With New Metastases
From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.
Number of Patients by Highest Grade Adverse Event Reported
From randomization to last follow-up. Follow-up schedule: Arm 1: 3 mos. after randomization / Arm 2: weekly during SBRT and the last day of SBRT; both arms: then every 3 mos. to 24 mos., then annually. Maximum follow-up at time of analysis was 63 months.
Progression-free Survival in the Presence or Absence of Circulating Tumor Cells (CTCs)
From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.
Study Arms (2)
Standard of Care (SOC)
NO INTERVENTIONStandard of care systemic therapy at the discretion of the treating physician.
Standard of Care + Ablation
EXPERIMENTALStandard of care systemic therapy plus ablation of all metastases by stereotactic body radiotherapy or surgery at the discretion of the treating physician.
Interventions
Patients receive 1, 3, or 5 fractions of radiation, beginning within 6 weeks of study entry. * For metastases in the peripheral lung, patients receive a single fraction of 30 Gy or 3 fractions for a total of 45 Gy. * For a single liver metastases, patients receive a single fraction of 30 Gy. * For metastases in the abdominal-pelvic or liver (\>1), patients receive 3 fractions for a total of 45 Gy. * For metastases in the central lung or mediastinal/ cervical lymph nodes, patients receive 5 fractions for a total of 50 Gy. * For spinal metastases, patients receive 1 fraction of 20 Gy. * For non-spinal osseous metastases, patients receive 3 fractions for a total of 30 Gy. * For thoracic/cervical spine metastases, patients receive 5 fractions for a total of 35 Gy.
All surgical resections will be approached with intent of an R0 resection (rendering the patient with no evidence of measureable disease and pathologic negative margin) and must occur within 6 weeks of study entry. Approach to surgery will be based upon the treating surgeon. An open, laparoscopic, or thorascopic approach is acceptable.
Eligibility Criteria
You may qualify if:
- A patient cannot be considered eligible for this study unless all of the following conditions are met.
- Pathologically confirmed metastatic breast cancer
- Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis;
- Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification
- Number of allowable metastases:
- =\< 4 metastases seen on standard imaging within 60 days prior to registration when all metastatic disease is located within the following sites:
- Peripheral lung
- Osseous (bone)
- Spine
- Central lung
- Abdominal-pelvic metastases (lymph node/adrenal gland)
- Liver
- Mediastinal/cervical lymph node
- All known disease amenable to metastasis-directed therapy with either SBRT or resection
- Note: Symptomatic bone metastasis are allowed if ablative therapy can be delivered
- +19 more criteria
You may not qualify if:
- Patients with any of the following conditions are NOT eligible for this study.
- Pathologic evidence of active primary disease or local/regional breast tumor recurrence at the time of registration;
- Co-existing or prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years; previous RT dose, date, fraction size, must be reported
- Metastases with indistinct borders making targeting not feasible
- Note: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician's judgment will be required
- Prior palliative radiation treatment for metastatic disease to be treated on the protocol (including radiopharmaceuticals)
- Metastases located within 3 cm of the previously irradiated structures:
- Spinal cord previously irradiated to \> 40 Gy (delivered in =\< 3 Gy/fraction)
- Brachial plexus previously irradiated to \> 50 Gy (delivered in =\< 3 Gy/fraction)
- Small intestine, large intestine, or stomach previously irradiated to \> 45 Gy (delivered in =\< 3 Gy/fraction)
- Brainstem previously irradiated to \> 50 Gy (delivered in =\< 3 Gy/fraction)
- Whole lung previously irradiated with prior percent volume receiving greater than or equal to 20 Gy (V20Gy)\> 30% (delivered in =\< 3 Gy/fraction)
- Primary tumor irradiated with SBRT
- Metastasis irradiated with SBRT
- Brain metastases
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologylead
- National Cancer Institute (NCI)collaborator
Study Sites (162)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
CTCA at Western Regional Medical Center
Goodyear, Arizona, 85338, United States
Arizona Center for Cancer Care-Peoria
Peoria, Arizona, 85381, United States
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
The Permanente Medical Group-Roseville Radiation Oncology
Roseville, California, 95678, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Naval Medical Center -San Diego
San Diego, California, 92134, United States
Kaiser Permanente Cancer Treatment Center
South San Francisco, California, 94080, United States
Saint Joseph's Medical Center
Stockton, California, 95204, United States
Gene Upshaw Memorial Tahoe Forest Cancer Center
Truckee, California, 96161, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907, United States
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909, United States
Poudre Valley Hospital
Fort Collins, Colorado, 80524, United States
Banner North Colorado Medical Center - Loveland Campus
Loveland, Colorado, 80539, United States
Helen F Graham Cancer Center
Newark, Delaware, 19713, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
Orlando Health Cancer Institute
Orlando, Florida, 32806, United States
Memorial Hospital West
Pembroke Pines, Florida, 33028, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Piedmont Hospital
Atlanta, Georgia, 30309, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
John B Amos Cancer Center
Columbus, Georgia, 31904, United States
CTCA at Southeastern Regional Medical Center
Newnan, Georgia, 30265, United States
Lewis Hall Singletary Oncology Center
Thomasville, Georgia, 31792, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Methodist Medical Center of Illinois
Peoria, Illinois, 61636, United States
Springfield Memorial Hospital
Springfield, Illinois, 62781, United States
Southwest Illinois Health Services LLP
Swansea, Illinois, 62226, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Midwestern Regional Medical Center
Zion, Illinois, 60099, United States
Ascension Saint Vincent Anderson
Anderson, Indiana, 46016, United States
Parkview Hospital Randallia
Fort Wayne, Indiana, 46805, United States
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845, United States
IU Health Ball Memorial Hospital
Muncie, Indiana, 47303, United States
Memorial Hospital of South Bend
South Bend, Indiana, 46601, United States
Ascension Via Christi Hospitals Wichita
Wichita, Kansas, 67214, United States
Owensboro Health Mitchell Memorial Cancer Center
Owensboro, Kentucky, 42303, United States
MaineHealth Coastal Cancer Treatment Center
Bath, Maine, 04530, United States
MaineHealth Maine Medical Center - Biddeford
Biddeford, Maine, 04005, United States
MaineHealth Maine Medical Center - Portland
Portland, Maine, 04102, United States
MaineHealth Cancer Care and IV Therapy - Sanford
Sanford, Maine, 04073, United States
MaineHealth Cancer Care Center of York County
Sanford, Maine, 04073, United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Greater Baltimore Medical Center
Baltimore, Maryland, 21204, United States
UM Upper Chesapeake Medical Center
Bel Air, Maryland, 21014, United States
Central Maryland Radiation Oncology in Howard County
Columbia, Maryland, 21044, United States
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805, United States
Lowell General Hospital
Lowell, Massachusetts, 01854, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183, United States
Michigan Healthcare Professionals Clarkston
Clarkston, Michigan, 48346, United States
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Michigan Healthcare Professionals Farmington
Farmington Hills, Michigan, 48334, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341, United States
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073, United States
Michigan Healthcare Professionals Troy
Troy, Michigan, 48098, United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Saint Luke's Hospital of Duluth
Duluth, Minnesota, 55805, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Missouri Baptist Medical Center
St Louis, Missouri, 63131, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Renown Regional Medical Center
Reno, Nevada, 89502, United States
Wentworth-Douglass Hospital
Dover, New Hampshire, 03820, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Virtua Memorial
Mount Holly, New Jersey, 08060, United States
Community Medical Center
Toms River, New Jersey, 08755, United States
Virtua Voorhees
Voorhees Township, New Jersey, 08043, United States
Lovelace Medical Center-Saint Joseph Square
Albuquerque, New Mexico, 87102, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Lovelace Radiation Oncology
Albuquerque, New Mexico, 87109, United States
New Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, 87109, United States
Christus Saint Vincent Regional Cancer Center
Santa Fe, New Mexico, 87505, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
University of Rochester
Rochester, New York, 14642, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Dickstein Cancer Treatment Center
White Plains, New York, 10601, United States
UNC Health Cancer Care Cary
Cary, North Carolina, 27518, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
UNC Health Cancer Care Garner
Garner, North Carolina, 27529, United States
Rex Hematology Oncology Associates-Blue Ridge
Raleigh, North Carolina, 27607, United States
UNC Health Cancer Care Raleigh
Raleigh, North Carolina, 27607, United States
UNC Health Cancer Care Wakefield
Raleigh, North Carolina, 27614, United States
Novant Cancer Institute Radiation Oncology - Supply
Supply, North Carolina, 28462, United States
Novant Health Cancer Institute Radiation Oncology - Wilmington
Wilmington, North Carolina, 28401, United States
Novant Health New Hanover Regional Medical Center
Wilmington, North Carolina, 28401, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Cleveland Clinic Akron General
Akron, Ohio, 44307, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
ProMedica Flower Hospital
Sylvania, Ohio, 43560, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030, United States
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
Guthrie Medical Group PC-Robert Packer Hospital
Sayre, Pennsylvania, 18840, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Self Regional Healthcare
Greenwood, South Carolina, 29646, United States
Gibbs Cancer Center-Pelham
Greer, South Carolina, 29651, United States
Spartanburg Medical Center
Spartanburg, South Carolina, 29303, United States
Texas Oncology-Austin Midtown
Austin, Texas, 78705, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Ogden Regional Medical Center
Ogden, Utah, 84405, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
Bon Secours Saint Mary's Hospital
Richmond, Virginia, 23226, United States
Legacy Salmon Creek Hospital
Vancouver, Washington, 98686, United States
Edwards Comprehensive Cancer Center
Huntington, West Virginia, 25701, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095, United States
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
London Regional Cancer Program
London, Ontario, N6A 4L6, Canada
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, K1H 8L6, Canada
CHUM - Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 3E4, Canada
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, H3H 2R9, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
King Faisal Specialist Hospital and Research Centre
Riyadh, 11211, Saudi Arabia
Yonsei University Health System-Severance Hospital
Seoul, 120-752, South Korea
Related Publications (1)
Petrelli F, Ghidini A, Ghidini M, Bukovec R, Trevisan F, Turati L, Indini A, Seghezzi S, Lonati V, Moleri G, Tomasello G, Zaniboni A. Better survival of patients with oligo- compared with polymetastatic cancers: a systematic review and meta-analysis of 173 studies. F1000Res. 2021 May 27;10:423. doi: 10.12688/f1000research.52546.4. eCollection 2021.
PMID: 35602670DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The trial completed accrual to the phase II portion and was temporarily closed to accrual on September 13, 2019, pending required follow-up for the full phase II analysis, per the protocol-specified statistical analysis plan. The full phase II primary endpoint analysis was done in December 2021 and did not support reopening accrual to address the phase III research question of overall survival.
Results Point of Contact
- Title
- Wendy Seiferheld
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
Steven J Chmura
NRG Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2015
First Posted
February 18, 2015
Study Start
December 24, 2014
Primary Completion
December 20, 2021
Study Completion
September 4, 2025
Last Updated
April 24, 2026
Results First Posted
February 8, 2023
Record last verified: 2026-04