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

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

The objective of this clinical trial is to determine whether the addition of immunotherapy combined with chemotherapy before chemoradiotherapy can increase the survival rate of patients with esophageal cancer. It will also assess the safety of this regimen. The primary questions it aims to answer include:

• Can the addition of immunotherapy combined with chemotherapy before chemoradiotherapy reduce the rate of disease recurrence among participants?
• What adverse reactions will participants experience during the treatment process?
• Compared with traditional chemoradiotherapy, will this regimen extend the survival period of participants?

Participants will:

• Undergo two cycles of immunotherapy combined with chemotherapy, administered every three weeks, followed by concurrent chemoradiotherapy, which includes 28 sessions of radiotherapy and five sessions of chemotherapy during the concurrent period; or proceed directly to concurrent chemoradiotherapy, and then receive two cycles of chemotherapy after the completion of radiotherapy, administered once a month.
• Undergo regular tests and examinations to evaluate efficacy and safety.
• Record symptoms that occur during the treatment period.

Inclusion Criteria:

1. Voluntarily participate and provide written informed consent;
2. Age 18-75 years, regardless of gender;
3. Histologically or cytologically confirmed esophageal squamous cell carcinoma;
4. Patients with inoperable esophageal cancer;
5. 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);
6. ECOG performance status 0-1;
7. Expected survival ≥ 3 months;
8. 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.

Exclusion Criteria:

1. Esophageal perforation or hematemesis;
2. 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;
3. Previous or ongoing treatment with other types of PD-1 antibodies, or prior immunotherapy targeting PD-1/PD-L1;
4. Known allergic reaction to macromolecular protein drugs or sintilimab or any of its formulation components;
5. 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;
6. 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;
7. 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);
8. Male or female participants of childbearing potential who refuse to use contraception during the study; or female patients who are pregnant or breastfeeding;
9. 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.