Phase II Study of Tislelizumab Combined With Induction Chemoradiotherapy and Subsequent Conversion Surgery for Locally Advanced Unresectable ESCC
This is a Phase II, open-label, single-arm, multicenter study evaluating the safety and efficacy of combining Tislelizumab with induction chemoradiotherapy (CRT), followed by conversion surgery, in patients with locally advanced, unresectable esophageal squamous cell carcinoma (ESCC). Patients will receive induction CRT with weekly paclitaxel and cisplatin along with Tislelizumab, followed by two cycles of consolidation Tislelizumab-chemotherapy. If the tumor becomes resectable, patients will undergo surgery. The primary goal is to assess the 2-year overall survival (OS) rate. Secondary outcomes include pathological complete response (pCR), conversion rate, R0 resection rate, disease-free survival (DFS), recurrence-free survival (RFS), and treatment-related adverse events.
• Patients had histologically confirmed, squamous-cell carcinoma of the esophagus
• Clinical T4 cancer, at least one unresectable metastatic regional lymph node due to invasion into an adjacent organ, or computed tomographic (CT) evidence of M1Lym, such as fixed supraclavicular nodes. Regional lymph nodes are defined on the basis of criteria specified by the eighth edition of the Union for International Cancer Control TNM staging system (Sobin and Wittekind, 2016).
• An age of at least 20 years
• An Eastern Cooperative Oncology Group performance-status score 0 or 1
• Adequate major organ functions
‣ WBC ≥3,500/mm3
⁃ Hemoglobin ≥ 9.0 g/dL
⁃ Platelet ≥ 80,000/mm3
⁃ Total bilirubin ≤ 2-fold the upper limit of normal (ULN)
⁃ ALT and AST ≤ 5-fold the ULN AND ≤200 U/L
⁃ PT, aPTT and INR ≤1.5-fold the ULN
⁃ Albumin ≥2.5 g/dL
⁃ Creatinine clearance ≥50 ml/min (based upon 24 hours urine collection or calculated by Cockroft-Gault formula)
• Male: ((140 - age) × weight \[kg\])/(72 × serum creatinine \[mg/dL\])
∙ Female: 0.85 x estimate for male
• Women of childbearing potential (including women with chemical menopause or no menstruation for other medical reasons) must agree to use contraception from the time of informed consent until 5 months or more after the last dose of investigational products. (Women of childbearing potential are defined as all women after the onset of menstruation who are not postmenopausal and have not been surgically sterilized (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopause is defined as amenorrhea for ≥12 consecutive months without specific reasons.)
• Men must agree to use contraception from the start of study treatment until 3 months or more after the last dose of the investigational product.
• Patients must be willing to undergo definitive resection with lymph node dissection
• Participants must have signed written informed consent form in accordance with regulatory and institutional guidelines.