Early Response-guided Sequential Radiotherapy After Chemoimmunotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma

Starting soon · Phase 2

Conditions studied: Esophageal Squamous Cell Carcinoma (ESCC)

In brief

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy with poor prognosis, particularly in patients with locally advanced disease. Neoadjuvant chemoimmunotherapy has shown promising antitumor activity and may improve pathological response; however, a proportion of patients achieve only stable disease (SD) or progressive disease (PD) after initial treatment and may have limited benefit from proceeding directly to surgery. This prospective, single-center, phase II clinical study aims to evaluate an early response-guided sequential selective radiotherapy strategy after neoadjuvant chemoimmunotherapy in patients with locally advanced, resectable ESCC. Patients will initially receive neoadjuvant chemotherapy combined with PD-1 inhibitor therapy. Based on radiological response assessment, patients with major response (complete response or partial response) will proceed directly to radical surgery, whereas patients with insufficient response (stable disease or progressive disease but still considered resectable) will receive sequential chemoradiotherapy followed by surgery. The study aims to assess the safety and efficacy of this individualized treatment strategy, with primary evaluation focusing on pathological response, surgical outcomes, and treatment-related adverse events. Exploratory analyses will investigate potential biomarkers associated with treatment response and prognosis.

Key facts

Study ID

NCT07721103

Run by

Tianjin Medical University Cancer Institute and Hospital

People needed

110

Starts

2026-07-14

Expected to finish

2031-12-31

Last updated by the study team

2026-07-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must meet all of the following criteria:
• Provide written informed consent before enrollment.
• Age >18 years, male or female.
• Histologically confirmed thoracic esophageal squamous cell carcinoma (ESCC).
• Locally advanced, resectable disease according to AJCC/UICC 8th edition TNM staging system, defined as:
• cT3-4aN0-2M0 or cT1-2N1-2M0;
• No evidence of distant metastasis;
• Considered initially resectable by a multidisciplinary surgical team.
• Patients who have received neoadjuvant chemoimmunotherapy and have measurable disease response assessment according to RECIST v1.1, including complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).
• At least one measurable lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival time >6 months.
• Adequate organ function meeting the following criteria:
• Bone marrow function:
• Absolute neutrophil count ≥1,500/mm³;
• Platelet count ≥100,000/mm³;
• Hemoglobin ≥9 g/dL.
• Renal function:
• Serum creatinine ≤1.5 mg/dL and/or creatinine clearance ≥60 mL/min.
• Hepatic function:
• Total bilirubin ≤1.5 × upper limit of normal (ULN);
• AST and ALT ≤1.5 × ULN.
• Participants of childbearing potential must agree to use medically approved contraception during study treatment and for 3 months after completion of treatment. Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days before enrollment and must not be breastfeeding.
• Willingness and ability to comply with study procedures, safety assessments, and survival follow-up.

You may not qualify if…

• Participants will be excluded if any of the following criteria apply:
• Evidence of distant metastasis.
• Previous or concurrent malignancy, except adequately treated basal cell carcinoma of skin or cervical carcinoma in situ.
• Previous thoracic radiotherapy.
• Previous treatment with PD-1, PD-L1, or CTLA-4 inhibitors, or known hypersensitivity to PD-1 inhibitors or macromolecular protein products.
• Active autoimmune disease or history of clinically significant autoimmune disease requiring systemic treatment.
• Current use of immunosuppressive therapy or systemic corticosteroids exceeding the equivalent of prednisone 10 mg/day within 2 weeks before enrollment.
• Clinically significant ascites or pleural effusion requiring therapeutic drainage.
• Uncontrolled cardiovascular disease, including:
• NYHA class II or higher heart failure;
• Unstable angina;
• Myocardial infarction within 1 year;
• Clinically significant arrhythmias requiring treatment.
• Significant coagulation abnormalities, bleeding tendency, or ongoing thrombolytic/anticoagulant therapy.
• Active gastrointestinal disorders associated with bleeding or perforation risk, including esophageal varices, active gastric/duodenal ulcer, ulcerative colitis, portal hypertension, or active tumor bleeding.
• History of severe bleeding, clinically significant hemoptysis, or thromboembolic events within specified periods.
• Active infection or unexplained fever >38.5°C before treatment initiation.
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks before study treatment.
• History or evidence of interstitial lung disease, pulmonary fibrosis, radiation pneumonitis, drug-induced pneumonitis, pneumoconiosis, or severe pulmonary impairment.
• Known immunodeficiency, including HIV infection, or active hepatitis infection requiring exclusion according to protocol criteria.
• Participation in another clinical trial within 1 month before enrollment or concurrent systemic anticancer therapy.
• Receipt of live vaccines within 4 weeks before treatment or planned live vaccination during study treatment.
• Known history of substance abuse, alcoholism, or drug abuse.
• Inability or unwillingness to comply with study-related procedures, examinations, or required costs.
• Any other medical, psychological, social, or safety-related condition judged by the investigator to make the participant unsuitable for study participation.

Where it is running

• Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital — Tianjin, China

Full record on ClinicalTrials.gov

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