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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Unresectable; Esophageal Squamous Cell Carcinoma by AJCC V8 Stage
• Intervention / Treatment: Drug: tislelizumab+ Paclitaxel + Cisplatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongjing Jiang, MD,PhD; Phone Number: 18622221069; Email: jianghongjing@tmu.edu.cn
• Study Contact Backup: Name: xiaobin shang, MD,PhD; Phone Number: 18622221071; Email: shangxiaobin@tmu.edu.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Hongjing Jiang
      • Contact: Hongjing Jiang, MD,PhD; Phone Number: 18622221069; Email: jianghongjing@tmu.edu.cn
      • Contact: xiaobin shang, MD,PhD; Phone Number: 18622221071; Email: shangxiaobin@tmu.edu.cn
      • Principal Investigator: Hongjing Jiang, MD,PhD
      • Sub-Investigator: Xiaobin Shang, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed esophageal squamous cell carcinoma;
2. Unresectable cT4a/N3(stage ⅣA) (AJCC 8 TNM classification);
3. Have a performance status of 0 or 1 on the ECOG Performance Scale;
4. Age 18-75 years old, both men and women;
5. Be willing and able to provide written informed consent/assent for the trial;
6. Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation;
7. 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;
8. 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:

1. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer;
2. Ineligibility or contraindication for esophagectomy;
3. 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;
4. 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);
5. Has severe hypersensitivity and adverse events (≥Grade 3) to any PD-1/PD-L1 inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tislelizumab+ Paclitaxel+Cisplatin; Paclitaxel 135mg/m2 , D1; Cisplatin 80mg/m2, D1; tislelizumab 200mg D2 ; totally 2-4 cycles	Drug: tislelizumab+ Paclitaxel + Cisplatin; tislelizumab combined with chemotherapy; Other Names: conversion therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Principal Investigator: Hongjing Jiang, MD，phD, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: July 4, 2022
• First Submitted That Met QC Criteria: July 7, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: E20220333A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No