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

Sponsor
SWOG Cancer Research Network
Study ID
NCT07578116
Phase
PHASE3
Status
Not Yet Recruiting

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Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

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

Study Details

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.

Key Dates

Start date
Mar 9, 2027
Status verified
May 2026
Primary completion
May 31, 2032
Completion
May 31, 2033

Study Design

Enrollment
562 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Step 1 (HER2-targeted systemic therapy, STS/SRT)
    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.
  • Experimental: Step 2 Cohort A, Arm 1 (locoregional, SBRT, systemic therapy)
    See Detailed Description.
  • Experimental: Step 2 Cohort A, Arm 2 (systemic therapy)
    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.
  • Experimental: Step 2 Cohort B (systemic therapy)
    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.

Primary Outcome Measure

Overall survival (OS) (Cohort A) [ Time Frame: From date of Step 2 registration to date of death, assessed up to 10 years ]

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