Abemaciclib for Molecular Residual Disease Detected by Circulating Tumor DNA in HR+/HER2- Early Breast Cancer (ARCHE)

Phase 2 Study of Abemaciclib for Molecular Residual Disease Detected by Circulating Tumor DNA in HR+/HER2- Early Breast Cancer

The goal of this clinical study is to determine whether monitoring ctDNA and treating patients who become ctDNA-positive with abemaciclib can help prevent the recurrence of hormone receptor-positive, HER2-negative breast cancer after curative surgery and standard therapy. The study will also assess the safety of abemaciclib and the medical problems that may occur during treatment. Participants will receive routine follow-up after surgery, undergo regular blood tests to measure ctDNA, and, if ctDNA becomes positive, receive abemaciclib for a defined treatment period with scheduled clinic visits for examinations and safety assessments. Researchers will evaluate recurrence-free survival, distant recurrence-free survival, adverse events, the time between ctDNA positivity and clinical recurrence, and the rate of ctDNA clearance at the end of abemaciclib therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; ctDNA Monitoring
• Intervention / Treatment: Drug: Abemaciclib 150 MG Oral Tablet

Detailed Description

The purpose of this clinical study is to investigate whether identifying molecular relapse through ctDNA monitoring and initiating abemaciclib treatment at the time of ctDNA positivity can reduce the risk of recurrence in patients with hormone receptor-positive, HER2-negative early breast cancer who have completed curative surgery and standard adjuvant therapy. The study also aims to evaluate the safety profile of abemaciclib in this early-stage setting and to clarify how patients tolerate the treatment over time. Participants will undergo routine postoperative surveillance, including scheduled imaging and laboratory testing, as well as regular blood sampling for ctDNA analysis. When ctDNA becomes detectable, indicating minimal residual disease, participants will begin a predefined course of abemaciclib and attend clinic visits at regular intervals for physical examinations, toxicity assessments, and laboratory monitoring.

In addition to determining whether early intervention with abemaciclib can delay or prevent clinical recurrence, researchers will examine several key outcomes. These include invasive disease-free survival, distant recurrence-free survival, and the incidence of adverse events throughout the treatment period. The study will also measure the "lead time" between ctDNA positivity and radiologic or clinical recurrence, which may provide insight into the biological dynamics of disease relapse. Furthermore, researchers will evaluate ctDNA clearance at the completion of abemaciclib therapy, as ctDNA clearance may serve as an early indicator of treatment efficacy. Collectively, these results are expected to clarify the clinical utility of ctDNA-guided therapy escalation and to inform future strategies for preventing recurrence in early breast cancer.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kazuki Nozawa, MD; Phone Number: +81-52-851-5511; Email: kazuki.nozawa7@gmail.com

Study Locations

• Japan
  • Nagoya, Japan
    • Nagoya City University
    • Contact: Kazuki Nozawa, MD; Phone Number: +81-52-851-5511; Email: ncu-003@med.nagoya-cu.ac.jp

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed invasive breast cancer.
• ctDNA-positive after completion of definitive local/systemic therapy.
• Definitive breast surgery performed; axillary node status confirmed.
• HR-positive, HER2-negative disease.
• Tumor and nodal status meet predefined pathological risk criteria.
• ECOG PS 0 - 1.
• No bilateral breast cancer.
• Adequate recovery from prior therapy and acceptable organ function.
• No distant metastasis before registration.
• Appropriate contraception; informed consent obtained.

Exclusion Criteria:

• Active second malignancy.
• Prior CDK4/6 inhibitor use.
• Recent major surgery or active infection.
• Uncontrolled hypertension or significant cardiac disease.
• Recent thromboembolic events.
• Interstitial lung disease or active pneumonitis.
• Unrecovered toxicities from prior treatment.
• Active HIV, HBV, or HCV infection.
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Treatment for MRD positive; ctDNA-posotive during adjuvant treatment	Drug: Abemaciclib 150 MG Oral Tablet; Adding abemaciclib for 2-year with endcrine treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA clearance rate	The rate of change of ctDNA positive to negative during abemaciclib treatment	Within 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events		up to 2 years
Invasive disease-free survival (IDFS)	A measure of the time from study enrollment until any invasive recurrence, second primary cancer, or death occurs.	through study completion, an average of 3 year
Distant recurrence-free survival (DRFS)	The time from study enrollment to the development of distant metastatic recurrence or death.	through study completion, an average of 3 year
Lead time from ctDNA positivity to clinical recurrence	The interval between the first detection of ctDNA positivity and the confirmed clinical or radiologic recurrence of cancer.	through study completion, an average of 2 year

Collaborators and Investigators

• Sponsor: Nagoya City University
• Collaborators: Japanese Foundation for Cancer Research; National Cancer Center, Japan; Tohoku University; University of Tsukuba; Aichi Cancer Center; Gifu University Graduate School of Medicine
• Investigators: Study Director: Ryuta Asada, PhD, Nagoya City University

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): August 31, 2031

Study Registration Dates

• First Submitted: November 22, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Pharmaceutical Preparations; Dosage Forms; abemaciclib; Tablets
• Other Study ID Numbers: NCU-003-Abema; NCU (Other Identifier: Nagoya City University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: only IPD used in the results publication
• IPD Sharing Time Frame: 1 year after publication.
• IPD Sharing Access Criteria: All researcher
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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.: Yes