NCT06663787

Personalized Detection of ctDNA for Patients With HER2-Positive Metastatic Breast Cancer Who Achieved Durable Response by Anti-HER2 Treatment (HER2 CR)

• Status: Active Not Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 50 (estimated)
• Sponsor: Nagoya City University · Academic / Other
• Sex: Female
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

Anti-HER2 therapy, such as trastuzumab and pertuzumab, has significantly improved long-term survival in HER2-positive breast cancer. The updated data of the CLEOPATRA trial showed significant Kaplan-Meier curves, suggesting the potential for a cure. However, the efficacy of maintenance therapy in long-term responders remains unexplored. This study will assess MRD in unresectable HER2-positive breast cancer cases with long-term response using the Signatera™ ctDNA assay, which could contribute to future treatment strategy development.

Detailed description

More than 20 years have passed since the introduction of trastuzumab as a treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The additive effect of trastuzumab, an anti-HER2 antibody, was evaluated in combination with chemotherapy (paclitaxel or anthracycline plus cyclophosphamide) in previously untreated, unresectable HER2-positive breast cancer. The number of cases achieving long-term survival with anti-HER2 therapy has been increasing, and this trend is also observed in our institution. The treatment for unresectable breast cancer is systemic therapy, which is typically continued as long as it remains effective and side effects are tolerable. However, in cases of long-term response in HER2-positive breast cancer, the impact of continuing anti-HER2 therapy alone as maintenance therapy on prognosis and the safety of treatment discontinuation remains unclear. In recent years, the clinical application of circulating tumor DNA (ctDNA) has attracted attention for early diagnosis and detection of minimal residual disease. Signatera™, an assay developed by Natera Inc., detects minimal residual disease. It is a personalized ctDNA test for individual patients, and a study targeting breast cancer patients post-surgery reported a detection sensitivity exceeding 90% for variant allele frequencies (VAF) as low as 0.01%. This high sensitivity has been reported not only in breast cancer but also in other cancer types. However, there have been no reports of Signatera analysis in unresectable breast cancer. In this study, investigators will use Signatera™ to evaluate and analyze ctDNA status (ctDNA positive or negative) in cases of unresectable HER2-positive breast cancer that have achieved long-term response. By assessing ctDNA in such cases, this study may lead to new therapeutic strategies, such as de-escalating anti-HER2 therapy in ctDNA-negative cases.

Conditions

• Breast Cancer, Metastatic
• HER2 + Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab (Herceptin)	Continuing anti-HER2 treatment
DIAGNOSTIC_TEST	SIgnatera	A personalized, tumor-informed test.

Timeline

• Start date: 2024-04-01
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2024-10-29
• Last updated: 2026-04-13

Locations

4 sites across 2 countries: United States, Japan

Regulatory

• FDA-regulated device study