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

NCT ID: NCT06663787

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2025-12-31

Brief 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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Continuing anti-HER2 treatment

Breast cancer patients who are continuing complete response (CR) or partial response (PR) for more than two years of anti-HER2 treatment (trastuzumab, pertuzumab, T-DM1, and T-DXd)

Trastuzumab (Herceptin)

Intervention Type: DRUG

Continuing anti-HER2 treatment

SIgnatera

Intervention Type: DIAGNOSTIC_TEST

A personalized, tumor-informed test.

Follow up (stop anti-HER2 treatment)

Breast cancer patients who stopped anti-HER2 treatment with complete response (CR) or partial response (PR) after more than two years of anti-HER2 treatment(trastuzumab, pertuzumab, T-DM1, and T-DXd)

SIgnatera

Intervention Type: DIAGNOSTIC_TEST

A personalized, tumor-informed test.

Interventions

Trastuzumab (Herceptin)

Continuing anti-HER2 treatment

Intervention Type: DRUG

SIgnatera

A personalized, tumor-informed test.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Trastuzumab Emtansine; Trastuzumab Deruxtecan

Eligibility Criteria

Inclusion Criteria

• HER2 + metastatic breast cancer
• Pre / post menopausal
• Previously treated with anti-HER2 therapy
• Continuing CR or PR for more than 2 year

Exclusion Criteria

• Patients who were deemed inappropriate as research subjects based on the physician's judgment, such as those possibly receiving inappropriate treatment.

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Nagoya City University

OTHER

Sponsor Role: lead

Responsible Party

Kazuki Nozawa

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Natera

San Carlos, Texas, United States

Aichi Cancer Center

Nagoya, Aichi-ken, Japan

Nagoya City University

Nagoya, Aichi-ken, Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Tokyo, Tokyo, Japan

Countries

United States; Japan

Other Identifiers

80-24-0057

Identifier Type: OTHER

Identifier Source: secondary_id

HER2 CR

Identifier Type: -

Identifier Source: org_study_id