Breast CancerPhase 2NCT05721248
STOP-HER2: Stopping Trastuzumab in HER2+ MBC
A Phase 2 study testing Cessation of anti-HER2 treatment in people with Breast Cancer and Metastatic Breast Cancer, run by Dana-Farber Cancer Institute at 13 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Metastatic Breast Cancer, HER2-positive Breast Cancer
- What is being tested?
- Cessation of anti-HER2 treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 13 sitesUnited States
- Study dates
- 19 Apr 2023to Jun 2036
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Dana-Farber Cancer Insitute
Boston, Massachusetts, 02215
Duke University
Durham, North Carolina, 27710
DFCI @ Foxborough
Foxborough, Massachusetts, 02035
Baylor College of Medicine
Houston, Texas, 77030
Mayo Clinical Hospital Florida
Jacksonville, Florida, 32224
DFCI @ Merrimack Valley
Methuen, Massachusetts, 01844
DFCI @ Milford Regional Hospital
Milford, Massachusetts, 01757
Mayo Clinic Hospital Arizona
Phoenix, Arizona, 85054
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
DFCI @ South Shore Hospital
South Weymouth, Massachusetts, 02190
Georgetown University Medical Center
Washington D.C., District of Columbia, 02809
About this study
Official title: The STOP-HER2 Trial: A Phase 2 Study of Stopping Trastuzumab - Outcomes in Patients With HER2+ Metastatic Breast Cancer
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.
Read the 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.
- Being tested
- Cessation of anti-HER2 treatment
- Keywords
- Breast Cancer, Metastatic Breast Cancer, HER2-positive Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cessation of anti-HER2 treatmentOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Observational Continue Anti-HER2 Therapy | No intervention | 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). |
| Cohort 2: - Stop Anti-HER2 Therapy | Experimental | 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. Receives: Other: Cessation of anti-HER2 treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 1 year
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.
Measured: Up to 1 year
Secondary outcomes (4)
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.
Measured: Up to 1 year
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
Measured: Up to 3 years
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.
Measured: Up to 3 years
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.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2023
- Study start19 Apr 2023
- Primary completion22 Jun 2026
- Study completionJun 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Gateway for Cancer Research, Susan G. Komen Breast Cancer Foundation, Translational Breast Cancer Research Consortium, Johns Hopkins University
- Responsible party
- Principal investigator, Nancy Lin, MD, Dana-Farber Cancer Institute
- Investigators
- Nancy U Lin, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05721248
- Sponsor's protocol ID
- 22-655
- Other IDs
- 1K08CA252639-01A1
- Status last verified
- Aug 2026
- First submitted
- 1 Feb 2023
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The STOP-HER2 Trial: A Phase 2 Study of Stopping Trastuzumab - Outcomes in Patients With HER2+ Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT05721248
- Acronym / sponsor ID
- 22-655
- Keywords
- Breast Cancer, Metastatic Breast Cancer, HER2-positive Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Gateway for Cancer Research, Susan G. Komen Breast Cancer Foundation, Translational Breast Cancer Research Consortium, Johns Hopkins University
- Study start
- 19 Apr 2023 (actual)
- Primary completion
- 22 Jun 2026 (actual)
- Study completion
- Jun 2036 (estimated)
- First posted
- 9 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Observational Continue Anti-HER2 Therapy | No intervention | –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). |
| Cohort 2: - Stop Anti-HER2 Therapy | Experimental | Other: Cessation of anti-HER2 treatmentParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cessation of anti-HER2 treatmentCessation 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. | Other | Cohort 2: - Stop Anti-HER2 Therapy |
Primary outcome
1-year progression-free survival (PFS) Stopped Anti-HER2 Treatment
Time frame: Up to 1 year
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.
1-year progression-free survival (PFS) Continued Anti-HER2 Treatment
Time frame: Up to 1 year
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.
4 secondary outcomes
Clinical benefit rate (CBR)
Time frame: Up to 1 year
3-year Overall survival (OS)
Time frame: Up to 3 years
3-year progression-free survival (PFS)
Time frame: Up to 3 years
Probability of restarting anti-HER2 Treatment
Time frame: Up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy U Lin, MD principal investigator
Dana-Farber Cancer Institute
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cessation of anti-HER2 treatment in people with Breast Cancer and Metastatic Breast Cancer, run by Dana-Farber Cancer Institute at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year progression-free survival (PFS) Stopped Anti-HER2 Treatment (time frame: Up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026; AzTrials last refreshed its copy on 6 Nov 2026.