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

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.

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Key information

Conditions

Esophageal Cancer CtDNA Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms MRD Neoplasms Neoplasms by Site

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion Criteria

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.
No prior systemic therapy administered for the disease, and planned to receive definitive chemoradiotherapy (dCRT).
Having undergone 1021-gene large panel testing on tissue samples.
Aged 18-80 years old.
Expected overall survival ≥ 6 months.
ECOG performance status 0-1.
Normal blood biochemical parameters, with normal liver and kidney function.
Able to understand the study protocol, voluntarily participate in the study, and sign the informed consent form.
Good compliance, able to cooperate with specimen collection at all designated time points and provide relevant clinical data.
Exclusion Criteria

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

Treatment and study plan

Step-up therapy

Drug

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.

Standard treatment Routine treatment

Drug

Patients receive 2 cycles of consolidative intravenous chemotherapy and then proceed to routine follow-up. MRD testing is repeated after the completion of chemotherapy.

Primary outcomes

PFS

Time frame: 1 year after enrollment

Sponsors and collaborators

Lead sponsor

The First Affiliated Hospital with Nanjing Medical University

Other

Registry information

Important dates

Study start: 2025
Primary completion: 2027
Study completion: 2027
First posted: Jan 27, 2026
Registry last updated: Jan 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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