A Study of Surgery and Radiotherapy in People With Breast Cancer

A Randomized Phase II Study of Consolidative Surgery and Radiotherapy With Curative Intent for De Novo Oligometastatic HER2+ Breast Cancer [Ablation and Resection for the Consolidation of Oligometastatic HER2+ Breast Cancer (ARCHER)]

The researchers are doing this study to see if the combination of surgery, locoregional radiation therapy, SBRT (stereotactic body radiation therapy), and the usual approach is more effective in treating oligometastatic HER2-positive breast cancer than the usual approach alone. The researchers will also study the side effects of the study treatment.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab, Pertuzumab, Paclitaxel, or a combination of these drugs; Procedure: Lumpectomy or mastectomy; Radiation: Radiotherapy

Detailed Description

Prior to randomization, patients will receive standard of care first-line systemic therapy as defined by NCCN guidelines (paclitaxel, trastuzumab and pertuzumab at the time of study activation). Following a 3-12 month period without evidence of progression as determined by the treating clinician, patients may be registered and then randomly assigned in 1:1 fashion to one of two study arms. All patients will be followed until progression of disease or 3 years after randomization, whichever comes first. All HER2-directed agents are FDA-approved and administered per standard of care practice.

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Atif Khan, MD; Phone Number: 848-225-6334
• Study Contact Backup: Name: Lior Braunstein, MD; Phone Number: 201-775-7446; Email: braunstl@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
      • Contact: Lior Braunstein, MD; Phone Number: 201-775-7446
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Lior Braunstein, MD; Phone Number: 201-775-7446
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Lior Braunstein, MD; Phone Number: 201-775-7446
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities )
      • Contact: Lior Braunstein, MD; Phone Number: 201-775-7446
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Lior Braunstein, MD; Phone Number: 201-775-7446
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activites)
      • Contact: Lior Braunstein, MD; Phone Number: 201-775-7446
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Lior Braunstein, MD; Phone Number: 201-775-7446

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Pathologically-confirmed metastatic breast cancer.
• Oligometastatic breast cancer (≤5 discrete metastatic lesions) without CNS involvement; as seen on standard imaging during initial workup and monitoring prior to registration.
• HER2-positive breast cancer per CAP/ASCO guidelines as determined by staff pathologist (any estrogen or progesterone receptor status).
• Based on size and location, all metastatic sites can be safely treated with either SBRT or resection.
• Enrolled at least 3 months (and up to 12 months) after initiation of first-line systemic therapy AND without evidence of progression as determined by treating clinician (whether clinically or radiographically) during this window. (ie. in the judgement of the treating clinician, based on standard evaluations, all known disease must be controlled prior to enrollment).
• ECOG performance status 0-2; KPS 60-100

Exclusion Criteria:

• Any foci of disease progression during initial 3-12 months of first-line systemic therapy (as determined by treating clinician)
• Escalation of systemic therapy line due to progressive disease (i.e. initiated second-line therapy prior to enrollment).
• Comorbidities precluding receipt of radiotherapy, surgery or standard systemic therapy.
• Intracranial or intrathecal/intramedullary spinal disease (ie. CNS involvement is excluded from the study; epidural/vertebral disease is permitted)
• Prior cancer history requiring chemotherapy within the past 10 years (ie. prior cancers are permitted provided no chemotherapy was administered).

Inclusion of Underrepresented Populations

• Individuals of all races and ethnic groups are eligible for this trial. There is no bias towards age or race in the clinical trial outlined. This trial is open to the accrual of men and women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care arm; Continuation of first-line systemic therapy will receive the usual approach (drug therapy). Patients will be assigned to the continuation of first-line systemic therapy for an indefinite period per the standard of care. Escalation of systemic-therapy line is at the discretion of the treating physician per standard of care.	Drug: Trastuzumab, Pertuzumab, Paclitaxel, or a combination of these drugs; Continue to receive the standard treatment you have already started, which includes trastuzumab, pertuzumab, paclitaxel, or a combination of these drugs. This treatment is not part of the study and will be decided by your regular treating physician.
Experimental: Consolidation arm; Patients will receive surgery, locoregional radiation therapy, SBRT, and the usual approach	Procedure: Lumpectomy or mastectomy; Resection of the primary breast tumor (ie. lumpectomy when possible or mastectomy when breast conservation not possible). Surgical resection of the primary breast tumor is to be performed per standard guidelines as applied to localized disease. Breast conserving surgery (ie. lumpectomy) is allowable per patient preference when supported by standard surgical practice. Mastectomy is preferred when breast conservation is declined by the patient, or if breast conservation would otherwise not be feasible in the early-stage setting (e.g. large tumor:breast volume ratio, inability to achieve negative margins with breast conservation, etc); Radiation: Radiotherapy; Radiotherapy will be delivered using external beam radiation per the guidelines.Radiotherapy will be delivered using external beam radiation per the guidelines set forth below, targeting two main compartments: Patients will undergo radiotherapy to the breast/chest wall, and regional nodal basins (including the axilla, supraclavicular fossa and internal mammary chain) per the standard adjuvant approach for locally advanced disease, and; Patient will undergo stereotactic body radiotherapy (SBRT) or similarly-ablative approaches to sites of distant disease, including all observable foci and those that may have since resolved radiographically during systemic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	with PFS defined as the time of randomization to the date of clinical or radiographic disease progression or death (by any cause in the absence of progression).	3 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Gateway for Cancer Research
• Investigators: Principal Investigator: Lior Braunstein, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2025
• Primary Completion (Estimated): September 17, 2029
• Study Completion (Estimated): September 17, 2029

Study Registration Dates

• First Submitted: June 30, 2025
• First Submitted That Met QC Criteria: June 30, 2025
• First Posted (Actual): July 8, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radiotherapy; Ablation; Resection; Consolidative surgery; 25-145
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Therapeutics; Surgical Procedures, Operative; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Trastuzumab; Paclitaxel; Radiotherapy; Mastectomy, Segmental; pertuzumab; Mastectomy
• Other Study ID Numbers: 25-145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No