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RECRUITING Phase 3 ClinicalTrials.gov

Adding Surgery and Radiation to the Usual Treatment for HER2-Positive Breast Cancer That Had Already Spread at Diagnosis

Sponsor: SWOG Cancer Research Network • ClinicalTrials.gov ID: NCT07578116

Registry updated: 2026-10-13
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Description

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.

Interventions

  • Biopsy Procedure (Procedure)
    Undergo biopsy
  • Biospecimen Collection (Procedure)
    Undergo collection of blood samples
  • Breast Conservation Treatment (Procedure)
    Undergo breast conserving therapy
  • Computed Tomography (Procedure)
    Undergo CT and/or PET/CT
  • Cyclin-Dependent Kinase 4 Inhibitor (Drug)
    Given CDK4/6 inhibitor
  • Cyclin-Dependent Kinase 6 Inhibitor (Drug)
    Given CDK4/6 inhibitor
  • Echocardiography Test (Procedure)
    Undergo ECHO
  • HER2-targeted Therapy (Drug)
    Receive HER2-targeted systemic therapy
  • Hormone Therapy (Drug)
    Given endocrine therapy
  • Magnetic Resonance Imaging (Procedure)
    Undergo MRI
  • Mammography (Procedure)
    Undergo mammography
  • Pertuzumab (Biological)
    Given pertuzumab
  • Positron Emission Tomography (Procedure)
    Undergo PET/CT
  • Radiation Boost (Radiation)
    Undergo RT boost
  • Radiation Therapy (Radiation)
    Undergo RT
  • Stereotactic Body Radiation Therapy (Radiation)
    Undergo SBRT
  • Stereotactic Radiosurgery (Radiation)
    Undergo SRS/SRT
  • Taxane Compound (Drug)
    Given taxane therapy
  • Total Mastectomy (Procedure)
    Undergo total mastectomy
  • Trastuzumab (Biological)
    Given trastuzumab
  • Trastuzumab Deruxtecan (Biological)
    Given T-DXd
  • Trastuzumab Emtansine (Biological)
    Given T-DM1
  • Ultrasound Imaging (Procedure)
    Undergo ultrasound

Eligibility criteria

Inclusion Criteria: * 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 * 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

Conditions

Anatomic Stage IV Breast Cancer AJCC v8 Metastatic HER2-Positive Breast Carcinoma Oligometastatic Breast Carcinoma

Locations

  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro — Jonesboro, Arkansas, United States
  • Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States
  • Smilow Cancer Hospital Care Center-Fairfield — Fairfield, Connecticut, United States
  • Smilow Cancer Hospital Care Center at Greenwich — Greenwich, Connecticut, United States
  • Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States
  • Smilow Cancer Hospital-Hamden Care Center — Hamden, Connecticut, United States
  • Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
  • Yale University — New Haven, Connecticut, United States
  • Yale-New Haven Hospital North Haven Medical Center — North Haven, Connecticut, United States
  • Smilow Cancer Hospital Care Center at Long Ridge — Stamford, Connecticut, United States
  • Smilow Cancer Hospital-Torrington Care Center — Torrington, Connecticut, United States
  • Smilow Cancer Hospital Care Center-Trumbull — Trumbull, Connecticut, United States
  • Smilow Cancer Hospital-Waterbury Care Center — Waterbury, Connecticut, United States
  • Smilow Cancer Hospital Care Center - Waterford — Waterford, Connecticut, United States
  • Orlando Health Cancer Institute — Orlando, Florida, United States
  • OSF Saint Joseph Medical Center — Bloomington, Illinois, United States
  • Illinois CancerCare-Bloomington — Bloomington, Illinois, United States
  • Illinois CancerCare-Canton — Canton, Illinois, United States
  • Illinois CancerCare-Carthage — Carthage, Illinois, United States
  • Cancer Care Specialists of Illinois - Decatur — Decatur, Illinois, United States
  • Decatur Memorial Hospital — Decatur, Illinois, United States
  • Illinois CancerCare-Eureka — Eureka, Illinois, United States
  • Illinois CancerCare-Galesburg — Galesburg, Illinois, United States
  • Illinois CancerCare-Kewanee Clinic — Kewanee, Illinois, United States
  • Illinois CancerCare-Macomb — Macomb, Illinois, United States
  • Cancer Care Center of O'Fallon — O'Fallon, Illinois, United States
  • HSHS Saint Elizabeth's Hospital — O'Fallon, Illinois, United States
  • Illinois CancerCare-Ottawa Clinic — Ottawa, Illinois, United States
  • Illinois CancerCare-Pekin — Pekin, Illinois, United States
  • Illinois CancerCare-Peoria — Peoria, Illinois, United States
  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center — Peoria, Illinois, United States
  • OSF Saint Francis Medical Center — Peoria, Illinois, United States
  • Illinois CancerCare-Peru — Peru, Illinois, United States
  • Illinois CancerCare-Princeton — Princeton, Illinois, United States
  • Southern Illinois University School of Medicine — Springfield, Illinois, United States
  • Springfield Clinic — Springfield, Illinois, United States
  • Springfield Memorial Hospital — Springfield, Illinois, United States
  • Illinois CancerCare - Washington — Washington, Illinois, United States
  • Mercy Cancer Center-West Lakes — Clive, Iowa, United States
  • Iowa Methodist Medical Center — Des Moines, Iowa, United States
  • Broadlawns Medical Center — Des Moines, Iowa, United States
  • Mercy Medical Center - Des Moines — Des Moines, Iowa, United States
  • Mercy Medical Center-West Lakes — West Des Moines, Iowa, United States
  • Ascension Via Christi Hospitals Wichita — Wichita, Kansas, United States
  • Baptist Memorial Hospital and Cancer Center-Golden Triangle — Columbus, Mississippi, United States
  • Baptist Cancer Center-Grenada — Grenada, Mississippi, United States
  • Baptist Memorial Hospital and Cancer Center-Union County — New Albany, Mississippi, United States
  • Baptist Memorial Hospital and Cancer Center-Oxford — Oxford, Mississippi, United States
  • Saint Francis Medical Center — Cape Girardeau, Missouri, United States
  • Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States
  • Asplundh Cancer Pavilion — Willow Grove, Pennsylvania, United States
  • Smilow Cancer Hospital Care Center - Westerly — Westerly, Rhode Island, United States
  • Lexington Health — West Columbia, South Carolina, United States
  • Baptist Memorial Hospital and Cancer Center-Collierville — Collierville, Tennessee, United States
  • Baptist Memorial Hospital and Cancer Center-Memphis — Memphis, Tennessee, United States
  • Bon Secours Memorial Regional Medical Center — Mechanicsville, Virginia, United States
  • Bon Secours Saint Francis Medical Center — Midlothian, Virginia, United States
  • Bon Secours Saint Mary's Hospital — Richmond, Virginia, United States
  • Bon Secours Cancer Institute at Reynolds Crossing — Richmond, Virginia, United States
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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

View Official Record