Conversion of Tislelizumab Combined With Chemotherapy in Unresectable Esophageal Squamous Cell Carcinoma

Study Overview
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Brief Summary
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Whether the introduction of immunotherapy can transform unresectable esophageal cancer into resectable, or even achieve R0 surgical resection, has not been reported yet. We plan to conduct a prospective, single-center, single-arm phase II clinical study of the safety and efficacy of tislelizumab combined with chemotherapy in the treatment of unresectable esophageal squamous cell carcinoma.

Detailed Description
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For patients not eligible for R0 resection (defined as locally advanced unresectable esophageal cancer), preoperative treatment can theoretically transform the tumor into a resectable state. The current significance of transformation therapy is to reduce tumor volume and stage to achieve radical resection, eliminate micrometastases, and prevent a postoperative recurrence. There are few studies on the transformation therapy of esophageal squamous cell carcinoma. We plan to conduct a prospective, single-center, single-arm phase II clinical study of the safety and efficacy of tislelizumab combined with chemotherapy in the treatment of T4a/N3 esophageal squamous cell carcinoma.

Official Title
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A Prospective, Single-center, Single-arm Phase II Clinical Study of the Safety and Efficacy of Tislelizumab Combined With Chemotherapy in the Treatment of Unresectable Esophageal Squamous Cell Carcinoma

Conditions
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Esophageal Squamous Cell Carcinoma by AJCC V8 Stage, Unresectable

Intervention / Treatment
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* Drug: tislelizumab+ Paclitaxel + Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed esophageal squamous cell carcinoma; Unresectable cT4a/N3(stage ⅣA) (AJCC 8 TNM classification); Have a performance status of 0 or 1 on the ECOG Performance Scale; Age 18-75 years old, both men and women; Be willing and able to provide written informed consent/assent for the trial; Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation; Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the study medication's first dose. If the urine test is positive or cannot be confirmed as unfavorable, a serum pregnancy test will be required; Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly acquired is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. Exclusion Criteria: Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer; Ineligibility or contraindication for esophagectomy; Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug; Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs); Has severe hypersensitivity and adverse events (≥Grade 3) to any PD-1/PD-L1 inhibitors.

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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Accepts Healthy Volunteers

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+ Paclitaxel+Cisplatin<br>Paclitaxel 135mg/m2 , D1; Cisplatin 80mg/m2, D1; tislelizumab 200mg D2 ; totally 2-4 cycles | Drug: tislelizumab+ Paclitaxel + Cisplatin<br>* tislelizumab combined with chemotherapy<br>* Other names: conversion therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 Surgical Resection Rate . | R0 resection rate | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the rate of pathologic complete response (pCR) to the study regimen | The percentage of pathologic complete response at resection for patients who has completed the study regimen | 1 year | 
| Evaluate the rate of main pathologic response (MPR) to the study regimen. | Viable tumor comprised ≤ 10% of resected tumor specimens | 1 year | 
| Objective response rate (ORR) | Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions | 1 year | 
| Disease-free survival (DFS) | DFS is defined as the time interval between the date of enrollment and the date of the first documented evidence of relapse after radical resection at any site or death related to cancer | 3 years | 
| Overall survival (OS) | Time from the enrollment to death of any cause | 3 years |