Tislelizumab Combined With Neoadjuvant Radiotherapy and Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma.

Study Overview
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Brief Summary
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This study aimed to evaluate the safety and feasibility of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. The tumor microenvironment and circulating immunological biomarkers in these patients were further evaluated to explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. This study will provide valuable information for further prospective clinical trials of neoadjuvant anti-PD-1 and other immunotherapy in esophageal cancer patients.

Official Title
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Neoadjuvant Tislelizumab Combined With Chemoradiotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma : Single Arm Phase II Study

Conditions
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Advanced Esophageal Squamous Cell Cancer

Intervention / Treatment
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* Drug: Tislelizumab Combined With Neoadjuvant Radiotherapy and Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 Histologically or cytologically confirmed resectable squamous-cell esophageal cancer ( cT1-2N+/ cT3-4aN0-3M0) Eastern Cooperative Oncology Group (ECOG) status 0-1 Signed written informed consent prior to the implementation of any trial-related rocedures Adequate organ function, evidenced by laboratory results with no contraindications to chemotherapy Absolute neutrophil count ≥ 1,500 х109/l Thrombocytes ≥ 100 х 109/l Hemoglobin ≥ 90 mg/l Creatinine ≤ 1.5 x ULN or creatinine clearance (calculated using the Cockcroft-Gault formula) ≥40 mL/min Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN) Alkaline phosphatase (ALP) > 5 x ULN Bilirubin > 1.5 х ULN Exclusion Criteria: Patients diagnosed with any other malignant tumor Patients at risk for tracheoesophageal fistula or aortoesophageal fistula Have received prior therapy with: chemotherapy, radiation therapy,immune checkpoint inhibitor Insufficient caloric and/or fluid intake despite consultation with a dietitian and/or tube feeding Have an active infection requiring systemic therapy that has not resolved 3 days (simple infection, such as cystitis) to 7 days (severe infection, such as pyelonephritis) before the first dose of trial treatment Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung dysfunction A history of interstitial lung disease or non-infectious pneumonia Active autoimmune disease with systemic therapy (ie, use of disease modifiers, corticosteroids, or immunosuppressive drugs) in the past 2 years Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibody) and various viral hepatitis infections Patients who have received allogeneic stem cell or solid organ transplantation Women during pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab arm<br>Radiotherapy: PTV 41.4Gy in 23 Fractions，5 days per week; Chemotherapy: Paclitaxel (Albumin bound) (100mg/m2) and Cisplatin (75 mg/m2) for 5 weeks, concurrent with radiotherapy; Immunotherapy: Tislelizumab (200mg per 3 weeks) | Drug: Tislelizumab Combined With Neoadjuvant Radiotherapy and Chemotherapy<br>* Patients received tislelizumab at a fixed dose of 200 mg every three weeks (q3w, 21 days) for 2 cycles.<br>* Other names: Anti-PD-1 Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Pathological Response Rate | No more than 10% of tumor cells were found in neoadjuvant surgical specimens. | From date of surgery to 14 days later | 
| Pathologic complete response rate | Pathologic complete response rate | From date of surgery to 14 days later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Disease free survival will be calculated from the start of the treatment to the disease progression or death of any reason. | 24 months | 
| Incidence of Treatment-related Adverse Events | Number and percentage of cases of all adverse events | 8 weeks |