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

ConditionsAnatomic Stage IV Breast Cancer AJCC v8Metastatic HER2-Positive Breast CarcinomaOligometastatic Breast Carcinoma
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorSWOG Cancer Research Network

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

There are 5 or fewer intracranial lesions

Each intracranial lesions is no larger than 2cm in longest dimension

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Breast Conservation Treatment

    Procedure/Surgery

    Undergo breast conserving therapy

  • Computed Tomography

    Procedure/Surgery

    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/Surgery

    Undergo ECHO

  • HER2-targeted Therapy

    Drug

    Receive HER2-targeted systemic therapy

  • Hormone Therapy

    Drug

    Given endocrine therapy

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Mammography

    Procedure/Surgery

    Undergo mammography

  • Pertuzumab

    Biological/Vaccine

    Given pertuzumab

  • Positron Emission Tomography

    Procedure/Surgery

    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/Surgery

    Undergo total mastectomy

  • Trastuzumab

    Biological/Vaccine

    Given trastuzumab

  • Trastuzumab Deruxtecan

    Biological/Vaccine

    Given T-DXd

  • Trastuzumab Emtansine

    Biological/Vaccine

    Given T-DM1

  • Ultrasound Imaging

    Procedure/Surgery

    Undergo ultrasound

Treatment groups

562 Participants
are divided into 4 treatment groups
Group A: Step 1 (HER2-targeted systemic therapy, STS/SRT)Experimental treatment 10 interventions
Group B: Step 2 Cohort A, Arm 1 (locoregional, SBRT, systemic therapy)Experimental treatment 21 interventions
Group C: Step 2 Cohort A, Arm 2 (systemic therapy)Experimental treatment 18 interventions
Group D: Step 2 Cohort B (systemic therapy)Experimental treatment 12 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
From date of Step 2 registration to date of death, assessed up to 10 years
2

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.

Time frame
From date of Step 2 registration to date of first documentation of progression or recurrence or death, assessed at 3 and 5 years
3

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.

Time frame
From date of Step 2 registration to date of death, assessed at 3 and 5 years

Secondary outcomes

1

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.

Time frame
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
2

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.

Time frame
From date of Step 2 registration to date of death, assessed at 3 and 5 years and then up to 10 years
3

Duration of standard of care first line systemic therapy (Cohort B)

Time frame
From time of response assessment at end of Step 1 up to 10 years

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

SWOG Cancer Research Network

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: