STOP-HER2: Stopping Trastuzumab in HER2+ MBC

Breast Cancer Clinical Trial

Official title:

The STOP-HER2 Trial: A Phase 2 Study of Stopping Trastuzumab - Outcomes in Patients With HER2+ Metastatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05721248
• Other study ID #: 22-655
• Secondary ID: 1K08CA252639-01A
• Status: Recruiting
• Phase: Phase 2
• Start date: April 19, 2023
• Est. completion date: February 2036

Study information

• Verified date: May 2024
• Source: Dana-Farber Cancer Institute
• Contact: Heather A Parsons, MD, MPH
• Phone: (617) 632-3800
• Email: Heather_parsons[@]dfci.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 82
• Est. completion date: February 2036
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• HER2-positive Breast Cancer
• Metastatic Breast Cancer

Intervention

Other:
• 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.

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Insitute	Boston	Massachusetts
United States	Duke University	Durham	North Carolina
United States	DFCI @ Foxborough	Foxboro	Massachusetts
United States	Baylor College of Medicine	Houston	Texas
United States	Mayo Clinical Hospital Florida	Jacksonville	Florida
United States	DFCI @ Merrimack Valley	Methuen	Massachusetts
United States	DFCI @ Milford Regional Hospital	Milford	Massachusetts
United States	Mayo Clinic Hospital Arizona	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	DFCI @ South Shore Hospital	South Weymouth	Massachusetts
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (6)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Gateway for Cancer Research, Johns Hopkins University, National Cancer Institute (NCI), Susan G. Komen Breast Cancer Foundation, Translational Breast Cancer Research Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year progression-free survival (PFS) Stopped Anti-HER2 Treatment	The primary endpoint is one-year progression-free survival (PFS) per RECIST 1.1 assessed separately in the participants who agree to stop HER2 therapy and those who continue HER2 therapy.	Up to 1 year
Primary	1-year progression-free survival (PFS) Continued Anti-HER2 Treatment	The primary endpoint is one-year progression-free survival (PFS) per RECIST 1.1 assessed separately in the participants who agree to stop HER2 therapy and those who continue HER2 therapy.	Up to 1 year
Secondary	Clinical benefit rate (CBR)	Determine the clinical benefit rate (CBR) of re-initiation of anti-HER2 therapy for participants who experience disease progression after stopping anti-HER2 therapy. Clinical benefit rate is defined as CR, PR, or SD = 24weeks per RECIST 1.1. Clinical benefit rate after re-initiation of HER2 therapy will be reported with a 95% exact confidence interval.	Up to 1 year
Secondary	3-year Overall survival (OS)	Determine 3-year overall survival (OS) in participants in cohorts 1 and 2 using time-to-event analysis methods of Kaplan-Meier	Up to 3 years
Secondary	3-year progression-free survival (PFS)	Determine 3-year PFS in participants in cohorts 1 and 2 using time-to-event analysis methods of Kaplan-Meier.	Up to 3 years
Secondary	Probability of restarting anti-HER2 Treatment	Proportion of participants that restart anti-HER2 systemic therapy without progression of disease in participants stopping anti-HER2 therapy will be reported with a 95% exact confidence interval.	Up to 1 year