STOP-HER2: Stopping Trastuzumab in HER2+ MBC

NCT ID: NCT05721248

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-19
• Study Completion Date: 2036-02-29

Brief Summary

This study is being done to see if anti-HER2 treatment be safely stopped in patients with HER2-positive metastatic breast cancer (MBC) that have had exceptional response to treatment. Exceptional response" is considered as cancer progression being controlled for three years or more since starting anti-HER2 treatment.

Detailed Description

This is a single arm, phase II study of cessation of anti-HER2 systemic therapy in exceptional responders with HER2-positive metastatic breast cancer (MBC), defined as individuals free of disease progression after at least 3 years of first-line treatment.

This research study will include two different groups (cohorts) of patients. Those not wanting to stop anti-HER2 maintenance treatment will be included in a non-randomized, observational cohort (cohort 1). Those willing to stop maintenance anti-HER2 treatment you will be included in cohort 2.

This study is trying to understand whether blood samples that may contain traces of DNA from cancer, known as "circulating tumor DNA" or "ctDNA" are able to help identify which patients can successfully stop treatment without a change in their cancer.

The research study procedures include: an initial screening phase followed by periodic visits with blood work, questionnaires, and body scans.

It is expected that about 82 people will take part in this research study (52 in cohort 2 (stopping treatment), 30 in cohort 1 (continuing treatment). This study is expected to last 1 year with 10 years of follow up.

The Susan G. Komen Foundation, the Gateway for Cancer Research - both nonprofit foundations supporting cancer research - and the National Institutes of Health are supporting this research study by providing funds. This study is also being supported by Johns Hopkins University on behalf of the Translational Breast Cancer Research Consortium (TBCRC). The TBCRC is a group of academic medical centers across the United States that work together to conduct breast cancer research.

Conditions

Breast Cancer; Metastatic Breast Cancer; HER2-positive Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Observational Continue Anti-HER2 Therapy

Participants will have scans 30 days prior to starting study then undergo clinical follow-up 4-6 weeks after study initiation, at 12 weeks, and every 12 weeks thereafter. Visits will include interval history, physical exam, concomitant medications and blood draw for tumor marker assessment and research blood.

Participants will undergo restaging scans every 12 weeks (+/- 2 weeks).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Cohort 2: - Stop Anti-HER2 Therapy

Participants will have scans 30 days prior to starting study. Week 1 participants will stop anti-HER2 therapy then undergo clinical follow-up every 4-6 weeks, at 12 weeks, and every 12 weeks thereafter. Visits will include interval history, physical exam, concomitant medications and blood draw for tumor marker assessment and research blood.

Participants will undergo restaging scans every 12 weeks (+/- 2 weeks). Participants remaining progression-free after one year off treatment, may continue off anti-HER2 therapy indefinitely, with imaging surveillance suggested to be every 3-6 months at the discretion of the treating oncologist and will be followed up to 10 years Participants with disease progression after stopping anti-HER2 therapy, treatment is at discretion of the treating physician but resuming the pre-study regimen is strongly encouraged.

Group Type: EXPERIMENTAL

Cessation of anti-HER2 treatment

Intervention Type: OTHER

Cessation of anti-HER2 treatment with standard treatment described as trastuzumab (Herceptin) with or without pertuzumab (Perjeta) continued as long as it is working or significant side effects occur.

Interventions

Cessation of anti-HER2 treatment

Cessation of anti-HER2 treatment with standard treatment described as trastuzumab (Herceptin) with or without pertuzumab (Perjeta) continued as long as it is working or significant side effects occur.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years
• Participants must have histologically or cytologically confirmed unresectable locally advanced or metastatic invasive breast carcinoma that is HER2-positive by American Society of Clinical Oncology/College of American Pathologists 2018 criteria, as assessed by standard institutional guidelines (central testing is not required). Both estrogen receptor (ER)-positive/HER2-positive and ER-negative/HER2-positive will be eligible.
• Participants with ER-positive disease should continue endocrine therapy.
• Participants must be currently receiving first-line anti-HER2 therapy (any regimen) for metastatic disease and must have been on this therapy for at least 3 years without evidence of progressive disease according to RECIST 1.1 criteria. The following exceptions apply:
• Patients with history of brain-only progressive disease previously treated with local therapy (surgery and/or radiation therapy) are eligible, provided they meet all the following study criteria:

• Asymptomatic
• Not requiring anti-convulsant for symptomatic control
• Not requiring corticosteroids
• No evidence of interim central nervous system (CNS) progression between the completion of CNS-directed therapy and screening radiographic study
• Minimum of 2 years (24 months) between completion of CNS-directed therapy and study start
• Participants with history of oligo-progression (i.e., progressive disease of a single lesion) outside CNS treated with local treatment and/or change of endocrine therapy only are eligible, provided they meet the following criteria:

• No evidence of interval progression between completion of local treatment or endocrine therapy change and screening radiographic study
• Minimum 2 years (24 months) between completion of local therapy or treatment switch and study start
• CT scan within 30 days of study start without definite evidence of progressive disease in the opinion of the treating investigator.
• Available, representative archival formalin-fixed paraffin-embedded (FFPE) tumor tissue block from primary and/or metastatic site. If tissue block is unavailable, 20 unstained 10uM slides will be accepted (less than 20 slides may be acceptable with documentation of Sponsor-Investigator approval and would not require an eligibility exception). Tumor tissue must be received by coordinating site prior to study enrollment.
• ECOG performance status 0-1
• For intervention arm only (cohort 2): willingness to stop anti-HER2 systemic therapy
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Ability to understand the study requirements and document informed consent indicating awareness of the investigational nature and the risks of this study
• Participants with another prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of this trial are eligible

Exclusion Criteria

• Participants who are receiving any investigational agents to treat breast cancer
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• All English- speaking patients will participate in the PRO measures. Patients that do not read or understand English are eligible to participate but will be exempt from the patient completed questionnaires

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Gateway for Cancer Research

OTHER

Sponsor Role: collaborator

Susan G. Komen Breast Cancer Foundation

OTHER

Sponsor Role: collaborator

Translational Breast Cancer Research Consortium

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Nancy Lin, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nancy U Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Mayo Clinic Hospital Arizona

Phoenix, Arizona, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Mayo Clinical Hospital Florida

Jacksonville, Florida, United States

Dana-Farber Cancer Insitute

Boston, Massachusetts, United States

DFCI @ Foxborough

Foxborough, Massachusetts, United States

DFCI @ Merrimack Valley

Methuen, Massachusetts, United States

DFCI @ Milford Regional Hospital

Milford, Massachusetts, United States

DFCI @ South Shore Hospital

South Weymouth, Massachusetts, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Duke University

Durham, North Carolina, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

1K08CA252639-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22-655

Identifier Type: -

Identifier Source: org_study_id