Tislelizumab With Chemotherapy or Radiation for Neoadjuvant Therapy of Esophageal Squamous Cell Carcinoma (TINES) (TINES)

June 27, 2023 updated by: First Affiliated Hospital Xi'an Jiaotong University

A Randomized, Open-label, Uncontrolled Study of Tislelizumab in Combination With Chemotherapy or Radiation Therapy for Neoadjuvant Therapy for Resectable Thoracic Esophageal Squamous Cell Carcinoma (TINES)

Esophageal squamous cell carcinoma (ESCC), one of the most common subtypes of esophageal cancer, has a poor prognosis and low 5-year overall survival. At present, the treatment of ESCC includes chemotherapy, immunity, radiotherapy, surgery and other methods, and in recent years, the treatment regimen of immune combined chemotherapy has begun to show results in the treatment of esophageal cancer. Tislelizumab has demonstrated good efficacy in advanced esophageal cancer and in the second- and third-line treatment. At present, neoadjuvant immunization is carried out less, and neoadjuvant immunization plus chemoradiotherapy has been achieved With a pCR rate of 55.6 and AEs of grade III and above 65%, and studies have shown that radiotherapy has immunosensitizing and coordinating effects, whether immunotherapy combined with radiotherapy has a better efficacy is worth further investigation. This review intends to conduct a randomized, open-label, uncontrolled study of tislelizumab in combination with chemotherapy or radiation therapy for neoadjuvant therapy for resectable locally advanced thoracic esophageal squamous cell carcinoma with a view to providing a new option for resectable locally advanced ESCC.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

32

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • The First Affiliated Hospital of Xi'an Jiaotong University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • (1) The subjects voluntarily joined the study and signed the informed consent form, with good compliance and follow-up;
  • (2) 18 years old≤ age≤ 79 years old, male or female;
  • (3) ECOG score 0~1 points;
  • (4) Patients with pathological (histological or cytology) confirmed esophageal squaf cell carcinoma; According to the eighth edition of the clinical tumor TNM stage, subjects were resectable cT2-4aNanyM0;
  • (5) Have measurable lesions (according to RECIST 1.1 criteria, tumor lesion CT scan length diameter≥ 10mm lymph node lesion CT scan short diameter ≥15mm);
  • (6) Those who were first diagnosed with esophageal squamous cell carcinoma before enrollment and did not undergo radiotherapy, chemotherapy, immunity, surgery and targeted therapy;
  • (7) Able to eat a liquid diet or above, no signs before esophageal perforation or esophageal ulcers, and able to tolerate surgery;

  • (8) The main organs function normally, that is, meet the following standards:

    1. Routine blood examination must be consistent (no blood transfusion, no hematopoietic factor and no correction with drugs within 14 days): ANC≥1.5×109/L; PLT≥100×109；HB≥90g/L；
    2. Biochemical tests must meet the following standards: TBIL≤1.5×ULN; ALT、AST≤2.5×ULN； serum creatinine sCr≤1.5×ULN, endogenous creatinine clearance≥50mL/min (Cockcroft-Gault formula); ALB≥30g/L；
    3. The coagulation function must meet: INR≤1.5×ULN and APTT≤1.5×ULN;
    4. Normal or mild to moderate lung function and can tolerate esophageal cancer surgery. Preoperative lung function examination should meet: VC% > 60%; FEV1 > 1.2 L，FEV1% > 40%； DLco>40%。

Exclusion Criteria:

  • (1) Have any active autoimmune disease or history of autoimmune disease (as follows, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (may be included after hormone replacement therapy)); Patients with vitiligo or childhood asthma that have been in complete remission and do not require any intervention in adulthood are excluded, but patients requiring medical intervention with bronchodilators are not included;
  • (2) Patients with congenital or acquired immunodeficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B, hepatitis C or co-infection with hepatitis B and C;
  • (3) immunosuppressive drugs have been used within 14 days prior to first use of study drug, excluding nasal and inhaled corticosteroids or physiologic doses of systemic steroids (i.e., not more than 10mg/day prednisone or its equivalent);
  • (4) The patient lost ≥ 10% body weight within 6 months before enrollment, or the BMI < 18.5kg/m2, or PG-SGA reached grade C;
  • (5) Live attenuated vaccine within 4 weeks prior to the first dose or planned for the duration of the study;
  • (6) other malignant tumors in the past 3 years;
  • (7) uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, despite optimal medical therapy); Patients with a new diagnosis of angina within 3 months prior to screening or myocardial infarction events within 6 months prior to screening; Arrhythmias (including QTcF: ≥450ms for men and 470ms ≥ women) require long-term use of antiarrhythmic drugs and grade II cardiac insufficiency ≥ New York Heart Association;
  • (8) Those with a history of severe lung or heart disease;
  • (9) Complicated by severe infection (eg, requiring intravenous antibiotics, antifungal or antiviral drugs) within 4 weeks before the first dose, or unexplained fever >38.5°C during screening/before the first dose;
  • (10) Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
  • (11) Pregnant or lactating women; Patients of childbearing potential who are unwilling or unable to use effective contraception;
  • (12) Known allergic reactions, hypersensitivity reactions or intolerances to investigational drugs and their excipients;
  • (13) Subjects who are participating in other clinical studies or whose first dose is less than 4 weeks from the end of the previous clinical study (last dose), or who have 5 half-lives of the study drug;
  • (14) Subject has a known history of psychotropic substance abuse, alcohol or drug abuse;
  • (15) Any condition that the investigator believes is likely to harm the subject or cause the subject to be unable to meet or perform the study requirements;
  • (16) After neoadjuvant therapy, the patient cannot tolerate surgery or is not suitable for surgery due to the progression of the disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Chemotherapy
Drug: Tislelizumab + cisplatin + paclitaxel
Tislelizumab 200mgD1 + cisplatin 75mg/m^2D1 + paclitaxel 150mg/m^2D1 Q3W 3 cycles
Active Comparator: Radiotherapy
Drug: Tislelizumab + radiotherapy
Tislelizumab 200mgQ3W 3 cycles + radiotherapy (23 times in total, 1.8 Gy per dose, 5 times a week)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response rate (pCR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
postoperative pathological examination shows no carcinological tissue residue
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary pathologic response rate (MPR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
postoperative pathological examination shows a residual < of 10% of cancerous tissue
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
Objective response rate (ORR) of primary lesions (RECIST v1.1)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks

the proportion of patients whose tumors shrink to a certain amount and remain for a certain period of time under imaging measurements, including complete response (CR, Complete Response) and partial response (PR, partial response) cases CR is defined as the complete disappearance of all target lesions except nodular disease. All target nodules must be reduced to normal size (minor axis< 10 mm). All target lesions must be evaluated.

PR is defined as the sum of the diameters of all measurable target lesions less than 30% ≥ baseline. The target nodule is summed and the short diameter is used, while all other target lesions are combined and the longest diameter is used. All target lesions must be evaluated.
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
Disease-free survival (DFS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
the time between postoperative surgery and recurrence of disease or death (for any cause)
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
Over all survival (OS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
the time from postoperative surgery to death (for any reason)
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
Safety in the neoadjuvant phase and postoperative phase
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
according to the Common Acute and Subacute Toxicity Grading Standard (CTCAE 5.0), the adverse reactions after each immune combined radiotherapy or immune combined chemotherapy in the neoadjuvant therapy stage and the postoperative adverse reactions were evaluated
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
Quality of life measurement and evaluation 1
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
according to the QLQ-C30 scale of the Quality of Life Survey, the quality of life after neoadjuvant therapy was assessed
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
Quality of life measurement and evaluation 2
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks
according to the QLQ-OES18 special scale for esophageal cancer, the quality of life after neoadjuvant therapy was assessed
From date of randomization until the date of first documented progression or date of death from any cause whichever came first, up to 100 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital Xi'an Jiaotong University

Investigators

  • Principal Investigator: Junke Fu, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2022

Primary Completion (Estimated)

October 1, 2023

Study Completion (Estimated)

October 1, 2024

Study Registration Dates

First Submitted

October 20, 2022

First Submitted That Met QC Criteria

October 27, 2022

First Posted (Actual)

November 2, 2022

Study Record Updates

Last Update Posted (Actual)

June 29, 2023

Last Update Submitted That Met QC Criteria

June 27, 2023

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • No. XJTU1AF2022LSK-374

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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