Anatomic Stage IV Breast Cancer AJCC v8Phase 3NCT07578116
Adding Surgery and Radiation to the Usual Treatment for HER2-Positive Breast Cancer That Had Already Spread at Diagnosis
A Phase 3 study testing Biopsy Procedure, Biospecimen Collection and Breast Conservation Treatment in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic HER2-Positive Breast Carcinoma, run by SWOG Cancer Research Network at 59 sites in United States.
Trial summary
This phase III trial evaluates the effect of adding locoregional therapy (surgery and radiation) and metastasis-directed stereotactic body radiation therapy (SBRT) to standard systemic therapy following standard HER2-targeted systemic therapy, compared to standard systemic therapy alone, in treating patients with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Positive Breast Carcinoma, Oligometastatic Breast Carcinoma
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Breast Conservation Treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 562 participants
- Where
- 59 sitesUnited States
- Study dates
- 9 Mar 2027to 31 May 2033
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- REGISTRATION STEP 1 - SCREENING \& INITIAL TREATMENT:
- Participants must have histologically confirmed de novo metastatic (i.e. American Joint Committee on Cancer [AJCC] stage IV, no prior history of breast cancer) HER2+ breast cancer with 1 to 5 distant metastatic lesions (oligometastatic). Metastatic breast cancer must be histologically confirmed through biopsy of a distant metastatic lesion unless it is not feasible or safe to biopsy a metastatic lesion, then there must be unequivocal evidence of metastasis on imaging and laboratory studies. HER2+ status must be confirmed in the breast tumor and distant metastatic site as defined per NCCN guidelines version 4.2025
- NOTE: If HER2 positivity at metastatic site is equivocal due to limitations in HER2 analysis in bone, or it is not feasible or safe to biopsy the metastatic lesion, then HER2 positivity based on breast tumor only is acceptable. If there is no breast lesion, HER2+ must be confirmed in at least one metastatic site
- Participants with brain metastases are eligible if they meet all of the following criteria at baseline:
- There are 5 or fewer intracranial lesions
- Each intracranial lesions is no larger than 2cm in longest dimension
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- NOTE: The brain is counted as 1 distant site towards the oligometastatic definition. Brain imaging is not required for participants who have no neurological signs or symptoms suggestive of central nervous system (CNS) involvement; however, assessment of neurological symptoms and brain MRI is strongly encouraged to rule out CNS disease
- Participants must have no known leptomeningeal disease
- Participants must meet one of the following criteria prior to Step 1 registration:
- Treatment naïve and planning to initiate standard of care systemic HER2+ targeted treatment OR
- Have already initiated standard of care systemic HER2+ targeted treatment and have completed at least one (≥ 1) but no more than three (≤ 3) cycles prior to enrollment, without progression
- NOTE: Standard of care scans for baseline disease assessment must have been performed within 28 days prior to initiation of treatment
- Participants must not be receiving or planning to receive any investigational systemic therapy during study before disease progression
- Participants must not have received whole brain irradiation
- NOTE: Participants with up to five brain metastases may have received SRS/SRT either before or after initiation of systemic therapy. If lesions are small and asymptomatic and the participant is receiving CNS penetration they may be managed with observation
- Participants must be ≥ 18 years old at the time of registration
- Participants must have Zubrod performance status of 0-2
- Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
- Participants must be able to safely receive the physician's choice of standard of care systemic HER2+ targeted treatment per the current Food and Drug Administration (FDA)-approved package insert(s), treating physician's discretion, and institutional guidelines
- Participants must be candidates for definitive surgical and radiotherapeutic management of locoregional disease opinion per the discretion of the treating physician
- Participants must be able to receive ablative dose stereotactic body radiation therapy (SBRT) to all metastatic lesions identified at baseline, in the opinion of the treating physician
- Participants must be offered the opportunity to participate in specimen banking
- NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
- Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and CIRB regulations
- REGISTRATION STEP 2 - COHORT ASSIGNMENT AND RANDOMIZATION:
- COHORT A: Participants must be registered to Step 2 within 14 days of staging scans performed after completing Step 1 systemic therapy
- COHORT A: Participants must have standard of care (SOC) staging scans and breast imaging performed following 12-24 weeks (minimum of 4 cycles) of initial systemic therapy and within 14 days prior to Step 2 registration
- COHORT A: Participants must have experienced partial or complete response in the breast (in the opinion of the treating physician) following 12-24 weeks of initial systemic therapy based on staging scans performed within 14 days prior to Step 2 registration
- Participants with breast lesion(s) at diagnosis must have a clinical response on breast imaging per the treating physician
- Metastatic lesions, as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) and bone response criteria, must have at least stable disease
- Brain metastases treated with SRS/SRT must have at least stable disease as per Response Assessment in Neuro-Oncology Brain Metastases (RANO BM) and must not require steroid treatment
- Participants with no known breast lesions at diagnosis must have at least partial response in the metastatic sites as assessed by RECIST and bone response criteria
- NOTE: The same imaging modality must be used as in Step 1
- COHORT A: Participants must be eligible for definitive surgical and radiotherapeutic management of locoregional disease per the discretion of the treating physician
- COHORT A: Participants must not have metastatic lesions that are not amenable to ablative dose stereotactic body radiation therapy (SBRT)
- Lung lesions that completely resolve after systemic therapy will not be targeted with SBRT, as it is not possible to achieve dose build-up
- The development of new sclerotic bone lesions after systemic therapy is not to be interpreted as disease progression, and all such lesions should be targeted with SBRT
- COHORT B: Participants must be registered to Step 2 within 14 days of staging scans performed after completing Step 1 systemic therapy
- COHORT B: Participants must have standard of care (SOC) staging and breast imaging performed following 12-24 weeks (minimum of 4 cycles) of initial systemic therapy and within 14 days prior to Step 2 registration
- COHORT B: Participants must experience clinically stable disease or progression following 12-24 weeks (minimum of 4 cycles) of initial systemic therapy and within 14 days prior to Step 2 registration
- Participants must have progression in metastatic lesions as assessed by RECIST and bone response criteria or may have stable disease in metastatic lesions by RECIST and bone response criteria if there is progression or no clinical response in the breast
- Participants with known breast lesion must have progression or no clinical response on breast imaging as per the treating physician
- NOTE: The same modality must be used as in Step 1
Who cannot join
None listed.
Trial locations and contacts
59 sites in 1 country. Contact the study team or a site near you to ask about taking part.
59 sites in 1 country
United States59 sites, 59 recruiting
- Recruiting
OSF Saint Joseph Medical Center
Bloomington, Illinois, 61701
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Canton
Canton, Illinois, 61520
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Site Public Contact, 573-334-2230, sfmc@sfmc.net
Bryan A. Faller
- Recruiting
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
Site Public Contact, 515-241-3305
Richard L. Deming
- Recruiting
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Philip E. Lammers
- Recruiting
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Philip E. Lammers
- Recruiting
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Decatur Memorial Hospital
Decatur, Illinois, 62526
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Site Public Contact, 515-241-6727
Seema Harichand-Herdt
- Recruiting
Broadlawns Medical Center
Des Moines, Iowa, 50314
Site Public Contact, 515-282-2200
Seema Harichand-Herdt
- Recruiting
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
Site Public Contact, 515-241-3305
Richard L. Deming
- Recruiting
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Philip E. Lammers
- Recruiting
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Smilow Cancer Hospital-Hamden Care Center
Hamden, Connecticut, 06518
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, 72401
Site Public Contact, 870-936-7066, Emily.Carvell@bmhcc.org
Philip E. Lammers
- Recruiting
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Bon Secours Memorial Regional Medical Center
Mechanicsville, Virginia, 23116
Site Public Contact, 804-893-8978, anne_carmellat@bshsi.org
William J. Irvin
- Recruiting
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Philip E. Lammers
- Recruiting
Bon Secours Saint Francis Medical Center
Midlothian, Virginia, 23114
Site Public Contact, 804-893-8978, anne_carmellat@bshsi.org
William J. Irvin
- Recruiting
Baptist Memorial Hospital and Cancer Center-Union County
New Albany, Mississippi, 38652
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Philip E. Lammers
- Recruiting
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Orlando Health Cancer Institute
Orlando, Florida, 32806
Site Public Contact, 321-841-7246, CancerClinicalTrials@orlandohealth.com
Shane R. Stecklein
- Recruiting
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi, 38655
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Philip E. Lammers
- Recruiting
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Peoria, Illinois, 61615
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Peru
Peru, Illinois, 61354
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Site Public Contact, 215-600-9151, ONCTrialNow@jefferson.edu
Elena Shagisultanova
- Recruiting
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Bon Secours Saint Mary's Hospital
Richmond, Virginia, 23226
Site Public Contact, 804-893-8978, anne_carmellat@bshsi.org
William J. Irvin
- Recruiting
Bon Secours Cancer Institute at Reynolds Crossing
Richmond, Virginia, 23230
Site Public Contact, 804-893-8978, Anne_caramella@bshsi.org
William J. Irvin
- Recruiting
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Site Public Contact, 217-545-7929
Bryan A. Faller
- Recruiting
Springfield Clinic
Springfield, Illinois, 62702
Site Public Contact, 800-444-7541
Bryan A. Faller
- Recruiting
Springfield Memorial Hospital
Springfield, Illinois, 62781
Site Public Contact, 217-528-7541, pallante.beth@mhsil.com
Bryan A. Faller
- Recruiting
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, 06902
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Illinois CancerCare - Washington
Washington, Illinois, 61571
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Lexington Health
West Columbia, South Carolina, 29169
Site Public Contact, 803-935-8300, research@lexhealth.org
Steven A. Madden
- Recruiting
Mercy Medical Center-West Lakes
West Des Moines, Iowa, 50266
Site Public Contact, 515-241-3305
Richard L. Deming
- Recruiting
Smilow Cancer Hospital Care Center - Westerly
Westerly, Rhode Island, 02891
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Mariya Rozenblit
- Recruiting
Ascension Via Christi Hospitals Wichita
Wichita, Kansas, 67214
Site Public Contact, 316-291-4774, research@viachristi.org
Dennis F. Moore
- Recruiting
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
Site Public Contact, 215-600-9151, ONCTrialNow@jefferson.edu
Elena Shagisultanova
About this study
Official title: Randomized Phase III Trial of Multimodality Therapy Versus Standard of Care Systemic Therapy in HER2 Positive (HER2+) De Novo (AJCC Stage IV) Oligometastatic Breast Cancer With Response to Initial Chemotherapy
This phase III trial evaluates the effect of adding locoregional therapy (surgery and radiation) and metastasis-directed stereotactic body radiation therapy (SBRT) to standard systemic therapy following standard HER2-targeted systemic therapy, compared to standard systemic therapy alone, in treating patients with HER2-positive stage IV breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or to a limited number of sites (oligometastatic). The usual approach for patients with (oligo)metastatic HER2-positive breast cancer is systemic drug treatment, which means medicines that travel through the whole body to treat both the breast and any areas where the cancer has spread. There are a number of approved HER2-targeted systemic therapy regimens available to patients. These typically include immunotherapy and/or chemotherapy. Immunotherapy drugs may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Unlike systemic therapy, locoregional therapies like surgery and radiation are focused treatments at the site of disease, delivered with the intent of sparing healthy tissues. Breast surgeries such as breast conserving therapy or total mastectomy are procedures in which the cancerous breast tissue (and healthy breast tissue in the case of total mastectomy) are surgically removed from the body. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Adding locoregional therapy, as well as metastasis-directed SBRT, to standard systemic therapy may help patients with (oligo)metastatic, HER2-positive stage IV breast cancer live longer overall or before their cancer progresses, and may help more patients achieve no evidence of disease, when compared to standard systemic therapy alone.
Read the detailed description
PRIMARY OBJECTIVES:
- To compare overall survival (OS) between participants with de novo stage IV oligometastatic HER2+ breast cancer who experience at least a partial response (PR) after initial systemic therapy similar to those used in stage III disease with curative intent, and are randomized to a multimodality approach including definitive locoregional therapy with surgery and radiotherapy and ablative intent stereotactic radiotherapy to detectable metastatic lesions followed by additional HER2-directed systemic therapy, similar to those used for residual disease after neoadjuvant therapy, (Cohort A, Arm 1) versus those who are randomized to physician's choice standard of care HER2-directed systemic therapies without local and metastasis directed ablative therapies (Cohort A, Arm 2). (Randomized Cohort A) II. To evaluate the distribution of progression-free survival (PFS) and overall survival (OS) among participants with de novo stage IV oligometastatic HER2+ breast cancer who do not experience a response after systemic therapy. (Observational Cohort B)
SECONDARY OBJECTIVES:
- To compare progression-free survival (PFS) in Cohort A, Arm 1 (randomized to multimodality therapy) versus Cohort A, Arm 2 (randomized to standard of care HER2-directed systemic therapy). (Randomized Cohort) II. To compare PFS in Cohort A, Arm 1 per protocol (received all multimodality therapy as planned) versus Cohort A, Arm 2. (Randomized Cohort) III. To compare OS in Cohort A, Arm 1 per protocol (received all multimodality therapy as planned) versus Cohort A, Arm 2. (Randomized Cohort) IV. To assess duration of standard of care first line systemic therapy received from time of response assessment in Cohort B. (Observational Cohort)
BANKING OBJECTIVE:
- To bank specimens for future correlative studies.
OUTLINE:
STEP 1: Patients receive physician's choice of HER2-targeted systemic therapy according to National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO) guidelines until completion of at least 12 weeks (4 cycles) or up to 24 weeks (8 cycles) of HER2-targeted therapy prior to Step 2 registration. Patients with brain metastases may also undergo stereotactic radiosurgery (SRS)/stereotactic radiotherapy (SRT) at the discretion of the treating physician.
STEP 2: Patients with partial or complete response in the breast following completion of Step 1 are assigned to Cohort A. Patients with clinically stable or progressive disease following completion of Step 1 are assigned to Cohort B.
COHORT A: Patients are randomized to 1 of 2 arms.
ARM 1:
LOCOREGIONAL THERAPY: Patients undergo breast surgery (either breast conserving therapy or total mastectomy) within 4-6 weeks of completion of Step 1 systemic therapy. Within 8 weeks of breast surgery, patients undergo locoregional radiation therapy (RT) to the breast, with or without RT to the breast/chest wall and/or regional lymph nodes, over 5-16 fractions. Patients may undergo RT boost to the lumpectomy bed over 4-5 fractions at the discretion of the treating physician.
STEREOTACTIC BODY RADIATION THERAPY (SBRT): Within 4-6 weeks of completion of locoregional therapy, patients undergo SBRT, with or without concurrent adjuvant therapy (pertuzumab and trastuzumab, or trastuzumab emtansine [T-DM1], or trastuzumab deruxtecan [T-DXd] with or without pertuzumab), to all targetable metastatic lesions every other day for 1, 3, or 5 fractions over a maximum of 3 weeks.
POST-LOCOREGIONAL THERAPY AND SBRT: Following recovery from surgery, patients resume systemic therapy (T-DXd, or T-DM1, or T-DXd with or without pertuzumab, or taxane with trastuzumab and pertuzumab, or trastuzumab with pertuzumab) according to NCCN/ASCO guidelines for at least 1 year in the absence of disease progression or unacceptable toxicity. Patients who are estrogen receptor positive may also receive endocrine therapy, with or without CDK4/6 inhibitors, at the discretion of the treating physician for at least 5 years, in the absence of disease progression or unacceptable toxicity.
ARM 2: Patients continue systemic therapy (T-DXd, or T-DM1, or T-DXd with or without pertuzumab, or taxane with trastuzumab and pertuzumab, or trastuzumab with pertuzumab) according to NCCN/ASCO guidelines for at least 1 year in the absence of disease progression or unacceptable toxicity. Patients may receive locoregional therapy and/or SBRT according to standard of care only if required for palliative purposes.
COHORT B: Patients continue systemic therapy (T-DXd, or T-DM1, or T-DXd with or without pertuzumab, or taxane with trastuzumab and pertuzumab, or trastuzumab with pertuzumab) according to NCCN/ASCO guidelines in the absence of disease progression or unacceptable toxicity.
All patients also undergo echocardiography (ECHO), magnetic resonance imaging (MRI), mammography, ultrasound, computed tomography (CT), and/or positron emission tomography (PET)/CT throughout the trial. Patients may undergo optional biopsy and/or collection of blood samples throughout the trial.
After completion of study treatment, patients registered to Step 2 are followed up for 10 years.
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Positive Breast Carcinoma, Oligometastatic Breast Carcinoma
- Being tested
- Biopsy Procedure, Biospecimen Collection, Breast Conservation Treatment, Computed Tomography, Cyclin-Dependent Kinase 4 Inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood samples
Breast Conservation TreatmentProcedure or surgery
Also called BCS, BCT, Breast Conserving Surgery/Lumpectomy, Breast-Conserving Surgery
Undergo breast conserving therapy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT and/or PET/CT
Cyclin-Dependent Kinase 4 InhibitorDrug
Also called CDK4 Inhibitor
Given CDK4/6 inhibitor
Cyclin-Dependent Kinase 6 InhibitorDrug
Also called CDK6 Inhibitor
Given CDK4/6 inhibitor
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
HER2-targeted TherapyDrug
Receive HER2-targeted systemic therapy
Hormone TherapyDrug
Also called Chemotherapy-Hormones/Steroids, Endocrine Therapy, Hormonal, Hormonal Therapy
Given endocrine therapy
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
MammographyProcedure or surgery
Also called MG
Undergo mammography
PertuzumabBiological
Also called 2C4, 2C4 Antibody, BCD-178, EG1206A
Given pertuzumab
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT
Radiation BoostRadiation
Also called BOOST, Boost Radiation, Boost Radiation Therapy, Boost Radiotherapy
Undergo RT boost
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo RT
Stereotactic Body Radiation TherapyRadiation
Also called SABR, SBRT, Stereotactic Ablative Body Radiation Therapy
Undergo SBRT
Stereotactic RadiosurgeryRadiation
Also called SRS, Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy
Undergo SRS/SRT
Taxane CompoundDrug
Also called taxane, Taxanes
Given taxane therapy
Total MastectomyProcedure or surgery
Also called Simple Mastectomy
Undergo total mastectomy
TrastuzumabBiological
Also called ABP 980, ALT02, Biceltis, CANMab
Given trastuzumab
Trastuzumab DeruxtecanBiological
Also called DS-8201, DS-8201a, Enhertu, Fam-trastuzumab Deruxtecan-nxki
Given T-DXd
Trastuzumab EmtansineBiological
Also called Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO 132365
Given T-DM1
Ultrasound ImagingProcedure or surgery
Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography
Undergo ultrasound
| Study group | Role | What they receive |
|---|---|---|
| Step 1 (HER2-targeted systemic therapy, STS/SRT) | Experimental | Patients receive physician's choice of HER2-targeted systemic therapy according to NCCN/ASCO guidelines until completion of at least 12 weeks (4 cycles) or up to 24 weeks (8 cycles) of HER2-targeted therapy prior to Step 2 registration. Patients with brain metastases may also undergo SRS/SRT at the discretion of the treating physician. All patients also undergo ECHO, MRI, mammography, ultrasound, CT, and/or PET/CT throughout the trial. Patients may undergo optional biopsy and/or collection of blood samples throughout the trial. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Drug: HER2-targeted Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Mammography; Procedure: Positron Emission Tomography; Radiation: Stereotactic Radiosurgery; Procedure: Ultrasound Imaging |
| Step 2 Cohort A, Arm 1 (locoregional, SBRT, systemic therapy) | Experimental | See Detailed Description. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Breast Conservation Treatment; Procedure: Computed Tomography; Drug: Cyclin-Dependent Kinase 4 Inhibitor; Drug: Cyclin-Dependent Kinase 6 Inhibitor; Procedure: Echocardiography Test; Drug: Hormone Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Mammography; Biological: Pertuzumab; Procedure: Positron Emission Tomography; Radiation: Radiation Boost; Radiation: Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy; Drug: Taxane Compound; Procedure: Total Mastectomy; Biological: Trastuzumab; Biological: Trastuzumab Deruxtecan; Biological: Trastuzumab Emtansine; Procedure: Ultrasound Imaging |
| Step 2 Cohort A, Arm 2 (systemic therapy) | Experimental | Patients continue systemic therapy (T-DXd, or T-DM1, or T-DXd with or without pertuzumab, or taxane with trastuzumab and pertuzumab, or trastuzumab with pertuzumab) according to NCCN/ASCO guidelines for at least 1 year in the absence of disease progression or unacceptable toxicity. Patients may receive locoregional therapy and/or SBRT according to standard of care only if required for palliative purposes. All patients also undergo ECHO, MRI, mammography, ultrasound, CT, and/or PET/CT throughout the trial. Patients may undergo optional biopsy and/or collection of blood samples throughout the trial. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Breast Conservation Treatment; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Mammography; Biological: Pertuzumab; Procedure: Positron Emission Tomography; Radiation: Radiation Boost; Radiation: Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy; Drug: Taxane Compound; Procedure: Total Mastectomy; Biological: Trastuzumab; Biological: Trastuzumab Deruxtecan; Biological: Trastuzumab Emtansine; Procedure: Ultrasound Imaging |
| Step 2 Cohort B (systemic therapy) | Experimental | Patients continue systemic therapy (T-DXd, or T-DM1, or T-DXd with or without pertuzumab, or taxane with trastuzumab and pertuzumab, or trastuzumab with pertuzumab) according to NCCN/ASCO guidelines in the absence of disease progression or unacceptable toxicity. All patients also undergo ECHO, MRI, mammography, ultrasound, CT, and/or PET/CT throughout the trial. Patients may undergo optional biopsy and/or collection of blood samples throughout the trial. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Mammography; Biological: Pertuzumab; Procedure: Positron Emission Tomography; Biological: Trastuzumab; Biological: Trastuzumab Deruxtecan; Biological: Trastuzumab Emtansine; Procedure: Ultrasound Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS) (Cohort A)
The primary analysis to evaluate the primary objective in the randomized cohort will be an intent-to treat (ITT) comparison of Arm 1 versus Arm 2 using a stratified log-rank test including all randomized, eligible participants. The hazard ratio and 95% confidence interval (CI) will be estimated by Cox regression including the stratification factors as variables in the model. Primary analyses will be repeated among individuals with brain metastases to understand whether the effect of the intervention differs in this subgroup.
Measured: From date of Step 2 registration to date of death, assessed up to 10 years
Progression-free survival (PFS) (Observational Cohort B)
In the observational cohort, the primary objective will be evaluated by estimating 3- and 5-year survival and corresponding 95% CIs using the Kaplan-Meier estimator. All analyses in the observational cohort will be descriptive. Primary analyses will be repeated among individuals with brain metastases to understand whether the effect of the intervention differs in this subgroup.
Measured: From date of Step 2 registration to date of first documentation of progression or recurrence or death, assessed at 3 and 5 years
Overall survival (Observational Cohort B)
In the observational cohort, the primary objective will be evaluated by estimating 3- and 5-year survival and corresponding 95% CIs using the Kaplan-Meier estimator. All analyses in the observational cohort will be descriptive. Primary analyses will be repeated among individuals with brain metastases to understand whether the effect of the intervention differs in this subgroup.
Measured: From date of Step 2 registration to date of death, assessed at 3 and 5 years
Secondary outcomes (3)
Progression free survival (Cohort A)
The primary analysis will be an ITT comparison of Arm 1 versus Arm 2 using a stratified log-rank test including all randomized, eligible participants. The hazard ratio and 95% CI will be estimated by Cox regression including the stratification factors as variables in the model. In addition to the primary analyses, will estimate PFS at 3 years and 5 years in Arm 1 and Arm 2 and corresponding 95% CIs using the Kaplan-Meier estimator.
Measured: From date of Step 2 registration to date of first documentation of progression or recurrence or death, assessed at 3 and 5 years and then up to 10 years
Overall survival (Cohort A)
The primary analysis will be an ITT comparison of Arm 1 versus Arm 2 using a stratified log-rank test including all randomized, eligible participants. The hazard ratio and 95% CI will be estimated by Cox regression including the stratification factors as variables in the model. In addition to the primary analyses, will estimate OS at 3 years and 5 years in Arm 1 and Arm 2 and corresponding 95% CIs using the Kaplan-Meier estimator.
Measured: From date of Step 2 registration to date of death, assessed at 3 and 5 years and then up to 10 years
Duration of standard of care first line systemic therapy (Cohort B)
Measured: From time of response assessment at end of Step 1 up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2026
- Study start9 Mar 2027 (estimated)
- Primary completion31 May 2032 (estimated)
- Study completion31 May 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by SWOG Cancer Research NetworkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients are sequentially assigned to Step 1 and Step 2 and then assigned to Cohort A or B in parallel.
- Masking
- None (open label)
- Enrolment
- 562 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SWOG Cancer Research Network
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mariya Rozenblit, Principal investigator, SWOG Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07578116
- Sponsor's protocol ID
- S2511
- Other IDs
- NCI-2026-02627, S2511, S2511, U10CA180888
- Status last verified
- Oct 2026
- First submitted
- 4 May 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No