Based on ctDNA-MRD Guided Adjuvant Treatment Escalation After Definitive Chemoradiotherapy for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: a Study on Safety and Efficacy

January 19, 2026 updated by: The First Affiliated Hospital with Nanjing Medical University

Numerous studies have confirmed that ctDNA-MRD detection technology based on peripheral blood can identify minimal residual disease (MRD) following surgery and other curative treatments, indicating a higher risk of recurrence. Multiple exploratory studies in esophageal cancer have demonstrated that patients who are ctDNA-MRD positive after definitive chemoradiotherapy (dCRT) exhibit poorer progression-free survival (PFS) and a higher risk of recurrence. Furthermore, the recent NEXUS-1 translational study confirmed that 66.7% of unresectable patients achieved the goal of conversion surgery after receiving definitive chemoradiotherapy combined with immunotherapy. Notably, patients who were ctDNA-MRD positive after chemoradiotherapy had a significantly worse prognosis. These findings suggest that ctDNA-MRD status after chemoradiotherapy has prognostic stratification value and that consolidative immunotherapy is effective.

Based on these previous discoveries, this study aims to investigate the safety and efficacy of an escalated treatment strategy involving immunotherapy combined with chemotherapy for high-risk populations after definitive chemoradiotherapy for esophageal cancer, guided by personalized MRD detection results.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

65

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Jiangsu Province Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

  • Inclusion Criteria

    1. Histologically confirmed locally advanced esophageal squamous cell carcinoma (ESCC), with clinical stage Ⅱ-Ⅳ unresectable disease (including unresectable cases, patients with surgical contraindications, or those who refuse surgery). According to the 8th edition AJCC staging system, the pretreatment clinical stage is defined as: cT1N2-3M0, cT2-4bN0-3M0; M1 disease is limited to non-regional lymph node metastases, excluding distant organ metastases.
    2. No prior systemic therapy administered for the disease, and planned to receive definitive chemoradiotherapy (dCRT).
    3. Having undergone 1021-gene large panel testing on tissue samples.
    4. Aged 18-80 years old.
    5. Expected overall survival ≥ 6 months.
    6. ECOG performance status 0-1.
    7. Normal blood biochemical parameters, with normal liver and kidney function.
    8. Able to understand the study protocol, voluntarily participate in the study, and sign the informed consent form.
    9. Good compliance, able to cooperate with specimen collection at all designated time points and provide relevant clinical data.

  • Exclusion Criteria

    1. Have participated in other clinical trials within 3 months prior to enrollment.
    2. Have a history of other malignant tumors within 3 years prior to the diagnosis of esophageal cancer.
    3. Have a history of severe mental illness.
    4. Patients who are unable to understand the study protocol and thus cannot cooperate, or who refuse to sign the informed consent form.
    5. Have contraindications to chemoradiotherapy.
    6. Have a history of autoimmune diseases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: MRD-positive groups
Assessed as MRD-positive based on ctDNA testing
Drug: Step-up therapy
Patients receive step-up therapy, consisting of 4 cycles of immunotherapy combined with intravenous chemotherapy, followed by immunotherapy plus oral chemotherapy for 6 months. MRD testing is repeated after the completion of immunotherapy combined with intravenous chemotherapy.
Sham Comparator: MRD-negative groups
Assessed as MRD-negative based on ctDNA testing
Drug: Standard treatment Routine treatment
Patients receive 2 cycles of consolidative intravenous chemotherapy and then proceed to routine follow-up. MRD testing is repeated after the completion of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
PFS
Time Frame: 1 year after enrollment
1 year after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2025

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

November 30, 2027

Study Registration Dates

First Submitted

January 19, 2026

First Submitted That Met QC Criteria

January 19, 2026

First Posted (Actual)

January 27, 2026

Study Record Updates

Last Update Posted (Actual)

January 27, 2026

Last Update Submitted That Met QC Criteria

January 19, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-SR-1071

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Esophageal Cancer

Clinical Trials on Step-up therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Georgia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe