Clinical trial NCT05603065: Tislelizumab With Chemotherapy or Radiation for Neoadjuvant Therapy of Esophageal Squamous Cell Carcinoma (TINES)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Tislelizumab
Neoadjuvant therapy
Immunotherapy
Esophageal squamous cell carcinoma
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2022-11-02
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cohort study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pathological complete response rate (pCR)
timeFrame: 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 outcomes:
measure: Primary pathologic response rate (MPR)
timeFrame: 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
measure: Objective response rate (ORR) of primary lesions (RECIST v1.1)
timeFrame: 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
measure: Disease-free survival (DFS)
timeFrame: 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
measure: Over all survival (OS)
timeFrame: 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
measure: Safety in the neoadjuvant phase and postoperative phase
timeFrame: 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
measure: Quality of life measurement and evaluation 1
timeFrame: 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
measure: Quality of life measurement and evaluation 2
timeFrame: 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
Other outcomes:
Locations:
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Junke Fu
role: PRINCIPAL_INVESTIGATOR
References: