Discontinuation of Maintenance HER-2 Directed Therapy in Long-Term Survivors of Metastatic HER-2 Positive Breast Cancer (Free-HER)

Free-HER: Discontinuation of Maintenance HER-2 Directed Therapy in Long-Term Survivors of Metastatic HER-2 Positive Breast Cancer

The purpose of this preliminary research study is to see if patients discontinuing maintenance Herceptin and/or other anti-HER-2 treatments with monitoring in addition to radiologic imaging and routine blood work will stay in complete radiological remission and to determine how long patients are able to stay in complete radiological remission without treatment.

Study Overview

• Status: Recruiting
• Conditions: Stage IV Breast Cancer; HER2-positive Metastatic Breast Cancer
• Intervention / Treatment: Other: Discontinuation of Anti-HER-2 Maintenance Treatment

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisa Krill Jackson, MD; Phone Number: 305-689-6500; Email: ekrill@med.miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: Elisa Krill Jackson, MD; Phone Number: 305-689-6500; Email: ekrill@med.miami.edu
      • Principal Investigator: Elisa Krill Jackson, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with a diagnosis of HER-2 positive metastatic (Stage IV) breast cancer.

2. Patients in complete radiological remission (CRR), including a stable bone scan, as determined by computed tomography (CT), positron-emission tomography (PET), or PET-CT.

   a. Patients with brain metastasis are allowed to participate as long as their disease has been treated and radiologically stable for at least 36 months.

3. Patients must be on the same or current anti-HER-2 directed therapy for at least 36 months.
4. Archived tumor biopsy available.
5. Patients with no evidence of circulating tumor deoxyribonucleic acid (ctDNA) as determined by the Signatera assay.
6. Patients willing to stop maintenance anti-HER-2 directed therapy with close monitoring.
7. Patients with an Eastern Cooperative Oncology Group (ECOG) performance score from 0 to 2.
8. Patients ≥ 18 years of age.
9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients with uncontrolled metastatic disease.
2. Patients whose disease has been controlled for less than 36 months on the same or current anti-HER-2 therapy.
3. Patients who are currently receiving or have received treatment for a secondary cancer other than resected non-melanoma skin cancer lesions or in situ cancer within the past 24 months.
4. Patients positive for ctDNA (which occurs when a patient's blood sample contains ≥2 target markers) with the Signatera assay.
5. Use of investigational drugs ≤ 28 days prior to study enrollment and during the study.
6. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or that makes participation in the trial to be not in the best interest of the patient in the opinion of the Investigator.
7. Patients with impaired decision-making capacity.

Patients who are found to be ctDNA+ at study entry will be recorded as a screen failure (Section 5.4). Their Signatera testing results will be provided to their treating physician to aid in clinical decision-making for disease management and treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-HER-2 Group; Participants in this group will be monitored to see if patients discontinuing maintenance of anti-HER-2 treatments with ctDNA monitoring in addition to radiologic imaging and routine blood work will stay in complete radiological remission. Participants will be in this group for up to 3 years.	Other: Discontinuation of Anti-HER-2 Maintenance Treatment; Patients assigned to this group will be asked to discontinue anti-HER-2 maintenance treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of maintaining remission after discontinuing use of anti-HER-2	The feasibility of maintaining remission of HER-2 will be measured as the proportion of patients who discontinue anti-HER-2 therapy and who remain in remission is assessed by monitoring ctDNA in the blood.	Up to 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of re-attain remission after ctDNA+ status	Ability to re-attain remission after ctDNA+ status is defined as returning to ctDNA- status within 6 months after testing ctDNA+ during the study. This is assessed by the monitoring of ctDNA in the blood of participants that have tested ctDNA positive after stopping anti-HER-2 maintenance therapy and chose to restart anti-HER-2 therapy.	Up to 72 months
Duration of response (DOR)	The duration of response (DOR) in study participants that have restarted anti-HER-2 therapy measures the time from is ctDNA+ status to overall response rate (ORR). This includes study participants that have ctDNA+ status and have chosen to either restart their previous anti-HER-2 maintenance therapy or have started a new anti-HER-2 therapy. The ORR is determined by blood and imaging monitoring.	Up to 72 months
Diagnostic Accuracy of ctDNA Monitoring Assay to Identify Disease Progression	Diagnostic accuracy is evaluated by comparing disease relapse and/or progression confirmed by imaging compared to study participants ctDNA status.	Up to 72 months

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Elisa Krill Jackson, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2023
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: July 17, 2023
• First Submitted That Met QC Criteria: July 17, 2023
• First Posted (Actual): July 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 20221166

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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