Neoadjuvant Cardonilizumab Combined With Chemotherapy Versus Neoadjuvant Concurrent Chemoradiotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: a Multicenter, Open-label, Randomized, Controlled Study
This is a multicenter, open-label, randomized, controlled clinical study to compare the efficacy and safety of cardonilizumab combined with neoadjuvant chemotherapy and surgery versus neoadjuvant chemoradiotherapy and surgery in locally advanced ESCC. Subjects were randomly divided into experimental group and control group, the experimental group received neoadjuvant immunotherapy concurrent chemotherapy regimen, the control group received neoadjuvant concurrent chemoradiotherapy regimen, and then received McKeown surgery. The primary outcome measures were complete pathological response (pCR), and the secondary outcome measures were major pathological response (MPR), EFS (event-free survival), OS (overall survival), overall response rate (ORR), decreased pathological stage, R0 resection rate, adverse events (AE), and perioperative complications
• Sign a written informed consent before implementing any procedures related to the trial;
• Male or female, 18 years old ≤75 years old;
• Patients with histologically proven ESCC with a pathological stage of cT1N2M0 or cT2-3N0-2M0 according to AJCC Version 8 TNM stage and eligible for R0 surgical resection prior to treatment;
• Have not received systematic treatment for the current disease, including surgical treatment, anti-tumor chemoradiotherapy/immunotherapy, etc.;
• Patients who agree to radical surgical treatment and are judged by the surgeon to have no surgical contraindications;
• ECOG score 0-1;
• Expected survival time \>6 months;
• For adequate organ function, subjects must meet the following laboratory criteria:
‣ The absolute value of neutrophil (ANC) ≥1.5x109/L in the past 14 days without the use of granulocyte colony-stimulating factor;
⁃ Platelets ≥100×109/L without blood transfusion in the past 14 days;
⁃ Hemoglobin \>9g/dL in the last 14 days without blood transfusion or use of erythropoietin;
⁃ Total bilirubin ≤1.5× upper limit of normal (ULN);
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤2.5×ULN
⁃ Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min;
⁃ Good coagulation function, defined as International standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
⁃ Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
⁃ The myocardial enzyme profile was within the normal range (if the researcher comprehensively judged that the simple laboratory abnormality was not clinically significant, it was also allowed to be included);
• For female subjects of reproductive age, a urine or serum pregnancy test should be performed within 3 days prior to receiving the first study drug administration (day 1 of cycle 1) and the results are negative. If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is requested. Women of non-reproductive age were defined as at least one year after menopause or having undergone surgical sterilization or hysterectomy;
• If there is a risk of conception, all subjects (male or female) are required to use contraception with an annual failure rate of less than 1% for the entire duration of treatment up to 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).