Exploratory Clinical Study of Camrelizumab Combined With Concurrent Chemoradiotherapy as an Organ-preserving Strategy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
This study is a prospective, exploratory clinical study aimed at evaluating the feasibility and safety of camrelizumab combined with synchronous chemoradiotherapy as an organ-preserving strategy for locally advanced resectable esophageal squamous cell carcinoma. The study targets patients with locally advanced resectable stage II/III/IVa (cT1b-4aN0-3M0) ESCC. A total of 164 subjects are expected to be enrolled. The study is a randomized, non-controlled, open-label trial. Subjects meeting the inclusion criteria will be randomly assigned in a 1:1 ratio to receive either camrelizumab combined with radiotherapy, albumin-bound paclitaxel, and carboplatin treatment (Cohort 1) or camrelizumab combined with radiotherapy and capecitabine treatment (Cohort 2). The screening period for the study is 28 days. After completing screening examinations and assessments, eligible subjects will be randomly assigned to the following treatment regimens. Cohort 1: * Camrelizumab: 200 mg on Day 1, every 3 weeks * Radiotherapy: 50-50.4 Gy / 25-28 fractions, Days 1-5, once a week * Albumin-bound paclitaxel: IV infusion, 60-80 mg/m², Day 1, weekly * Carboplatin: IV infusion, AUC=1-1.5, Day 1, weekly Each cycle lasts 3 weeks, with 2-4 cycles of medication. Efficacy evaluation (imaging and endoscopic examination) will be conducted within 6 weeks after the completion of treatment. If the efficacy evaluation indicates cCR, subjects will enter Group A1 and receive camrelizumab maintenance therapy (maximum 1 year). If the efficacy evaluation does not reach cCR, after consultation between the investigator and the subject, they will enter Group B1 to undergo radical surgery, followed by camrelizumab monotherapy maintenance treatment (maximum 1 year). Cohort 2: Camrelizumab: ivgtt, 200 mg, D1, Q3W Radiotherapy: 50-50.4 Gy / 25-28 fractions, D1-D5, QW Capecitabine: p.o. 625 mg/m², BID, D1-D14, Q3W; One cycle lasts 3 weeks, with 2-4 cycles of medication. Efficacy evaluation (imaging and endoscopy) will be conducted within 6 weeks after treatment completion. If the efficacy is assessed as cCR, the patient will enter Group A2: receive camrelizumab maintenance therapy (up to 1 year); if efficacy is not cCR, the patient will enter Group B2: undergo radical surgery, followed by camrelizumab monotherapy maintenance (up to 1 year). This study will follow up subjects for disease recurrence and disease-free survival for at least 2 years. After all subjects complete the treatment/termination visit, efficacy will be evaluated.
• 1\. Age ≥18 years old; 2. Histologically or cytologically confirmed esophageal squamous cell carcinoma (ESCC); 3. Patients with locally advanced resectable stage II/III/IVa (cT1b-4aN0-3M0) ESCC; 4. Have not received chemotherapy, radiotherapy, or surgical treatment for esophageal cancer; 6. ECOG performance status: 0-1; 7. Expected survival ≥12 weeks; 8. Within 7 days prior to enrollment, the participant's blood routine and biochemical indicators meet the following criteria:
‣ Hemoglobin ≥90 g/L; absolute neutrophil count (ANC) ≥1.5 × 10\^9/L; platelets ≥100 × 10\^9/L (patients must not have received blood transfusion or growth factor support within 14 days before blood sampling);
⁃ ALT and AST ≤2.5 times the upper limit of normal (ULN); ALP ≤2.5 times ULN;
⁃ Total serum bilirubin \<1.5 times ULN (patients with Gilbert's syndrome may enroll if total bilirubin \<3 times ULN);
⁃ Serum creatinine \<1.5 times ULN or estimated glomerular filtration rate ≥60 ml/min/1.73 m²;
⁃ Serum albumin ≥30 g/L;
⁃ International normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN, unless the patient is on anticoagulant therapy and PT value is within the expected therapeutic range;
⁃ Activated partial thromboplastin time (APTT) ≤1.5 times ULN. 9. Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%).
‣ 10\. Women of childbearing potential must agree to use contraceptive measures (such as intrauterine device, contraceptive pills, or condoms) during the study and for 6 months after the study; must have a negative serum or urine pregnancy test within 7 days prior to study enrollment, and must not be breastfeeding; men must agree to use contraceptive measures during the study and for 6 months after the study.
‣ 11\. No severe comorbidities that would result in a life expectancy of less than 5 years.
‣ 12\. Subjects voluntarily participate in this study, sign the informed consent form, have good compliance, and cooperate with follow-up.