Decreasing Treatment for Metastatic HER2-Positive Breast Cancer With Undectable Cancer Levels in Blood Tests.

NCT06450314 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-BCG-23122023-509811-98-00
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

Heroes is a multicentre, national, non-randomized, open-label, phase 2 study. The goal of this clinical trial is to evaluate the feasibility of therapeutic de-escalation in HER2-positive metastatic breast cancer with disease controlled after 2 years of maintenance treatment with anti-HER2 targeted therapy AND ctDNA negative testing. The main question it aims to answer is : • Is it possible to identify patients for whom temporary or permanent discontinuation of treatment is possible without impacting prognosis?

Conditions

Metastatic Breast Cancer; HER2-positive Breast Cancer

Keywords

de-escalation; ctDNA test

Outcome Measures

Primary Outcomes (1)

• Progression-free rate

  The progression-free rate (PFR) is the percentage of patient with disease progression defined as the time from the date of registration to the date of the first documented event among radiological progressions (RECIST 1.1), molecular progressions definitive as ctDNA-positive results, or death due to any cause, whichever occurs first.

  1 year

Secondary Outcomes (11)

• Progression-free survival

  1 year

• ctDNA dynamics

  1 year

• ctDNA positivity rate

  1 year

• Overall Survival

  1 year

• Molecular response

  1 year

Study Arms (1)

ctDNA negative cohort at baseline

EXPERIMENTAL

Patients with ctDNA negative test at baseline will stop their anti-HER2 targeted therapy during the study * In case of radiological progression with or without ctDNA positive test, prior treatment will be restarted or new anti-HER2 treatment will be initiated according investigator choice * In case of ctDNA positive test without radiological progression, prior treatment will be restarted.

Drug: Discontinuation of the anti-HER2 maintenance therapy; Device: Monitoring with signatera test

Interventions

Discontinuation of the anti-HER2 maintenance therapy DRUG

Heroes is a de-escalation study. Patient must have received continuous anti-HER2 targeted therapy (including Trastuzumab, Trastuzumab/Pertuzumab, Trastuzumab-Deruxtecan, T-DM1) for at least 2 years in any line setting for their HER2-positive metastatic breast cancer with complete response or partial response at last radiological assessment. Patients with ctDNA negative test at baseline will stop their anti-HER2 targeted therapy during the study

ctDNA negative cohort at baseline

Monitoring with signatera test DEVICE

ctDNA test will be performed at 1.5 month after inclusion and every 3 months during 2 years. Note: For the ctDNA negative patients who become ctDNA positive: ctDNA test will be performed once, 3 months after restarting treatment (+/-1 week).

ctDNA negative cohort at baseline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient's consent;
• Men or women ≥18 years of age;
• Documented diagnosis of locally advanced inoperable or metastatic histologically-proven HER2-positive breast cancer (HER2-positive is defined as HER2 3+ immunohistochemical overexpression, or the presence of HER2 amplification, according to ASCO-CAP guidelines);
• Must have an adequate archival tumor tissue sample available for next-generation sequencing (NGS) analysis by central laboratory, in order to design the ctDNA test (based on most recent available tumor tissue sample, metastatic biopsy (bone tissue excluded) and primary tumor authorised);
• Patient with Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) ≤1;
• Patient must have received continuous anti-HER2 targeted therapy (including Trastuzumab, Trastuzumab/Pertuzumab, Trastuzumab-Deruxtecan or T-DM1) treatment for at least 2 years in any line setting, for their locally advanced inoperable or metastatic HER2 + breast cancer (prior treatment interruption of 3 months maximum is allowed), with complete response or partial response at last radiological assessment;
• Note: the number of patients who received anti-HER2 targeted therapy in second line setting or more will be capped to 50% of the overall population
• In case of bone disease only, complete metabolic response in 18-FDG pet-scanner is required;
• Patient with treated (surgery and/or radiation therapy) and controlled primary tumor;
• Patients with ER-positive disease may or may not have received concomitant endocrine therapy (which must be continued if present). Concomitant ovarian blockade using Luteinizing Hormone-Releasing Hormone (LHRH) agonists is authorised as well;
• Adequate cardiac, renal, haematological and hepatic functions according to guidelines hospital;
• Non post-menopausal women and fertile men must agree to use adequate contraception methods during the study. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive;
• Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up;
• Patients must be affiliated to a Social Security System (or equivalent).

You may not qualify if:

• Any breast cancer progression over the past 2 years or at study entry;
• Patient concurrently using other approved or investigational antineoplastic agents than trastuzumab, pertuzumab, Trastuzumab-Deruxtecan, TDM-1 +/- endocrine therapy;
• Had an history of tumoral meningitis or clinically active central nervous system metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms;
• Subjects with curatively treated brain metastases (i.e., complete removal surgery or stereotactic radiotherapy) who are no longer symptomatic and do not require treatment with corticosteroids or anticonvulsants may be included in the study provided they have recovered from the acute toxicity of radiotherapy and there has been no progression of the brain metastases within the past 24 months.
• Subjects with brain metastases only or treated with whole brain radiotherapy will be excluded of the study
• Major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results;
• History of any prior ipsi or contralateral breast cancer (except in case of DCIS) unless if both primary tumors were confirmed to be HER2-positive;
• Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease and treatment for at least 3 years;
• Major surgery within 2 weeks prior to study entry;
• Pregnant women or women who are breast-feeding;
• Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;
• Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to patient enrolment and for the duration of the study);
• Persons deprived of their liberty or under protective custody or guardianship.

Sponsors & Collaborators

• UNICANCER: lead
• Natera, Inc.: collaborator

Study Sites (1)

Centre Eugène marquis

Rennes, 44229, France

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Thibault De la Motte Rouge, MD

  Centre Eugene Marquis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clara Guyonneau, PharmD

CONTACT

+33 (0) 1 44.23.04.65; c-guyonneau@unicancer.fr

Thibault De la Motte Rouge, MD

CONTACT

t.delamotterouge@rennes.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 10, 2024
• Study Start: January 25, 2025
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 15, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)