NCT06450314

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

De-escalation of Medical Therapies in HER2-positive Metastatic Breast Cancer in Long-term Persistent Response and Minimal Residual Disease Undetectable in Circulating Tumor DNA

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 170 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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?

Detailed description

Metastatic breast cancer remains a difficult disease to cure in the majority of cases. Improved biological knowledge has made it possible to separate these heterogeneous pathologies into several subtypes. For the HER2 subtype, which accounts for around 15% of breast cancers, very significant progress has been made in recent years with innovative treatments known as anti-HER2 therapies (trastuzumab, pertuzumab, T-DM1, T-DXd). Long-term disease control has been achieved in at least 20% of these patients with these new treatments. However, the treatments are continued indefinitely, impacting patients' quality of life through toxicity and chronic administration. It is possible that, for some patients, these treatments can be discontinued while maintaining surveillance. To assess this possibility, new biological tools, notably the search for circulating tumor DNA (ctDNA), look very promising for detecting any tumor cells in the body, even to very small traces (minimal residual disease). The primary objective of this trial is to evaluate the feasibility of therapeutic de-escalation (temporary or complete discontinuation) in patients with HER2-positive metastatic breast cancer whose disease is controlled after 2 years of maintenance treatment with anti-HER2 targeted therapy AND a negative ctDNA test.

Conditions

• Metastatic Breast Cancer
• HER2-positive Breast Cancer

Interventions

Type	Name	Description
DRUG	Discontinuation of the anti-HER2 maintenance therapy	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
DEVICE	Monitoring with signatera test	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).

Timeline

• Start date: 2025-01-25
• Primary completion: 2027-12-15
• Completion: 2029-12-15
• First posted: 2024-06-10
• Last updated: 2025-02-20

Locations

1 site across 1 country: France