Sintilimab Combined With Chemotherapy Induction Therapy Followed by CCRT vs. CCRT for Esophageal Cancer: A Randomized Controlled Phase Ⅲ Clinical Study

Prior treatment

• Previous or ongoing treatment with other types of PD-1 antibodies, or prior immunotherapy targeting PD-1/PD-L1;
• Active infection, or unexplained fever (body temperature \>38.5℃) within 2 weeks prior to screening (fever judged by the investigator to be due to the tumor itself may be allowed);

Other illness

• Esophageal perforation or hematemesis;
• Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (patients with hypothyroidism stable on hormone replacement therapy for ≥4 weeks with TSH/FT4 within normal range may be included); additionally, patients who have used immunosuppressants within 28 days will be excluded, except for steroid use for managing chemoradiation-related toxicities;
• Known allergic reaction to macromolecular protein drugs or sintilimab or any of its formulation components;
• Uncontrolled cardiac disease or clinical symptoms, such as: a. heart failure of NYHA class II or above; b. unstable angina; c. myocardial infarction within the past year; d. supraventricular or ventricular arrhythmias requiring clinical intervention;
• Congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10⁴ copies/mL), hepatitis C (positive HCV antibody with HCV-RNA above the lower limit of detection), or active tuberculosis;
• Other conditions judged by the investigator that may lead to premature termination of the study, such as co-existing severe diseases (including psychiatric disorders) requiring combined treatment, or family/social factors that may affect participant safety or integrity of the trial data.

Other

• Male or female participants of childbearing potential who refuse to use contraception during the study; or female patients who are pregnant or breastfeeding;

• Voluntarily participate and provide written informed consent;
• Age 18-75 years, regardless of gender;
• Histologically or cytologically confirmed esophageal squamous cell carcinoma;
• Patients with inoperable esophageal cancer;
• Clinical stage Ⅱ-ⅣA (AJCC 8th edition esophageal cancer staging system, including stage ⅣB with supraclavicular lymph node metastasis but excluding other distant metastatic stage ⅣB);
• ECOG performance status 0-1;
• Expected survival ≥ 3 months;
• No severe dysfunction of hematopoietic, cardiac, pulmonary, hepatic, or renal systems, nor immune deficiency; Neutrophils ≥ 1.5×10⁹/L; hemoglobin ≥ 9 g/dL; platelets ≥ 100×10⁹/L; total bilirubin ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; creatinine ≤ 1.5 × ULN.