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Perioperative Tislelizumab Plus Chemotherapy for Resectable Thoracic Oesophageal Squamous Cell Carcinoma

Primary Purpose

Esophageal Squamous Cell Carcinoma, Neoadjuvant Chemoimmunotherapy, Adjuvant Therapy

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Sponsored by
Guo Xufeng
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring esophageal Squamous Cell Carcinoma, neoadjuvant chemotherapy, neoadjuvant immunotherapy, adjuvant therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The patient volunteers to participate in the study, signs a consent form, has good compliance, and obeys the follow-up, and is willing and able to follow the protocol during the study; Histologically-confirmed squamous cell carcinoma; tumors of the esophagus are located in the thoracic cavity; Have not received systemic and local treatment for esophageal cancer; Pre-treatment staging as cT1b-3N1-3M0 or T3N0M0, American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition; Male or female, aged ≥18 and ≤75 years; The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score is 0 -1; R0 resection is expected; Adequate cardiac function. All patients should perform electrocardiogram (ECG), and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction >50%; Adequate respiratory function with forced expiratory volume in 1 second (FEV1) ≥ 1.2 L, FEV1% ≥ 50% and lung diffusing capacity for carbon monoxide (DLCO) ≥ 50% shown in pulmonary function tests; Adequate bone marrow function (white blood cells > 4×109/L, neutrophil > 1.5 ×109/L, hemoglobin > 90g/L, platelets > 100×109/L). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3× upper level of normal (ULN); Adequate liver function (total bilirubin <1.5× ULN, AST and ALT <2.5× ULN); Adequate renal function (glomerular filtration rate (GFR) >60 mL/min; serum creatinine (SCr) ≤120 μmol/L]; Fertile female subjects are required to have a negative serum or urine pregnancy test no later than 72 hours before starting the study drug administration, and to use effective contraception (such as an IUD, contraceptive pill, or condom) during the trial period and for at least 3 months after the last dose; For male subjects whose partners are women of reproductive age, effective contraception should be used during the trial period and within 3 months after the last dose. Exclusion Criteria: Unresectable factors, including those who are unresectable for tumor reasons or have surgical contraindications, or who refuse surgery; Patients with supraclavicular lymph node metastasis; Poor nutritional status, BMI<18.5Kg/m2; Patients could continue to be considered for enrollment if corrected with symptomatic nutritional support before enrollment and after assessment by the principal investigator Allergy to any drugs; Have received or are receiving any of the following treatments; a) any radiotherapy, chemotherapy or other antineoplastic drugs directed at the tumour; b) being treated with an immunosuppressive drug or systemic hormone for immunosuppression (at a dose of >10mg/ day of prednisone or equivalent) within 2 weeks before the first dose of the study drug; Inhaled or topical steroids and corticosteroid replacement at doses >10mg/ day of prednisone or equivalent were allowed in the absence of active autoimmune disease; c) received live attenuated vaccine within 4 weeks before the first dose of study drug; d) major surgery or severe trauma within 4 weeks before the first dose of study drug; Human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) active infection or known HIV seropositivity; including HBV or HCV surface antigen positive (RNA) Uncontrolled cardiac symptoms or diseases, including but not limited to: (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias without or poorly controlled after clinical intervention; Severe infection (CTCAE>2) occurred within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infectious complications; Prophylactic antibiotics were excluded if there was active pulmonary inflammation on chest imaging at baseline, if there were signs and symptoms of infection within 14 days before the first dose of the study drug, or if treatment with oral or intravenous antibiotics was required Participation in other drug clinical studies within 4 weeks before randomization; Patients with interstitial pneumonia or interstitial lung disease, or previous history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, or other subjects with pulmonary fibrosis, organized pneumonia (such as bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia that may interfere with the judgment and treatment of immune related pulmonary toxicity, or subjects with active pneumonia or severe lung function damage revealed by CT during screening; Active pulmonary tuberculosis; Patients with any active autoimmune disease or history of autoimmune disease and possible recurrence [including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients who can be controlled only by hormone replacement therapy can be enrolled)]; Patients with skin diseases that do not require systemic treatment, such as leukoplakia, psoriasis, alopecia, patients with type I diabetes that can be controlled by insulin treatment, or patients with a history of asthma, but have completely relieved in childhood and do not need any intervention, can be enrolled; Asthma patients who needed bronchodilators for intervention could not be enrolled; Patients have previously received an anti-PD-1,PD-L1 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways; Other malignancies that had been diagnosed within 5 years before the first dose of a study drug were considered unless cancers with a low risk of metastasis or death (5-year survival rate, >90%), such as adequately treated basal-cell or squamous-cell skin cancer or carcinoma in situ of the cervix, were considered. Pregnant or lactating women; The investigators determined that there were other factors that might have led to the forced discontinuation of the study, such as other serious medical conditions (including mental illness) requiring co-treatment, alcohol, substance abuse, family or social factors, and factors that might have affected the safety or adherence of the subjects.

Sites / Locations

  • Shanghai chest hospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adjuvant tislelizumab plus chemothearpy

Arm Description

Tislelizumab:200mg d1, q3w × 2 cycles,up yo 1 year; Nad-paclitaxel 260 mg/m2 d1 q3w 2 cycles;carboplatin AUC = 5 d1, q3w × 2 cycles.

Outcomes

Primary Outcome Measures

2-year disease-free survival in non-pCR patients
The time from the first day of surgery to the first occurrence of local or distant recurrence and metastasis or death from any cause in non-pCR patients

Secondary Outcome Measures

pCR rate
Pathological complete response (pCR) rate of all patients
major pathological response
MPR was defined as the presence of viable tumor cells≤10% in the resected tumor specimen
2-year DFS in pCR patients
The time from the first day of surgery to the first occurrence of local or distant recurrence and metastasis or death from any cause in pCR patients
R0 resection rate
No vital tumor is presented at the proximal, distal, or circumferential resection margin, then it is considered R0 resection
adverse events
Safety will be evaluated for all treated patients using CTCAE V 5.0.
overall survival
The date of death of any causes since the date of randomization.

Full Information

First Posted
September 10, 2023
Last Updated
September 24, 2023
Sponsor
Guo Xufeng
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1. Study Identification

Unique Protocol Identification Number
NCT06056336
Brief Title
Perioperative Tislelizumab Plus Chemotherapy for Resectable Thoracic Oesophageal Squamous Cell Carcinoma
Official Title
Perioperative Immunoagent (Tislelizumab) Plus Chemotherapy for Locally Advanced Resectable Thoracic Oesophageal Squamous Cell Carcinoma Trail:A Prospective Single-arm,Phase II Study (PILOT Trail)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 7, 2023 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Guo Xufeng

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to analyze esophageal cancer patients who underwent neoadjuvant immunotherapy with chemotherapy followed by esophagectomy to determine whether additional adjuvant therapy is associated with improved survival outcomes.
Detailed Description
Eligiled patients with pathologically confirmed thoracic esophageal squamous cell carcinoma and at clinical T1b-3N1-3M0 or T3N0M0 according to the eighth edition of American Joint Committee on Cancer staging will be allocated to neoadjuvant immunotherapy (tislelizumab 200mg d1, q3w × 2 cycles ) and chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with resected (R0) were assigned to receive tislelizumab ( at a dose of 200 mg every 3 weeks for 30 weeks) in pCR patients or adjuvant immunotherapy and chemothearpy for two cycles, and then tislelizumab ( at a dose of 200 mg every 3 weeks for 24 weeks) in non-pCR patients.The primary endpoint for this study is 2-year disease-free survival (DFS) in non-pCR patients.The secondary endpoints include pCR rate, major pathological response (MPR) rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival (OS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma, Neoadjuvant Chemoimmunotherapy, Adjuvant Therapy
Keywords
esophageal Squamous Cell Carcinoma, neoadjuvant chemotherapy, neoadjuvant immunotherapy, adjuvant therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
73 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Adjuvant tislelizumab plus chemothearpy
Arm Type
Experimental
Arm Description
Tislelizumab:200mg d1, q3w × 2 cycles,up yo 1 year; Nad-paclitaxel 260 mg/m2 d1 q3w 2 cycles;carboplatin AUC = 5 d1, q3w × 2 cycles.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
Albumin-bound Paclitaxel, Carboplatin
Intervention Description
Tislelizumab 200 mg q21d up to 1 year. Nad-paclitaxel 260 mg/m2, IV., every 3 weeks, 2-3 cycles. Carboplatin area under the curve = 5, IV., every 3 weeks, 2 cycles.
Primary Outcome Measure Information:
Title
2-year disease-free survival in non-pCR patients
Description
The time from the first day of surgery to the first occurrence of local or distant recurrence and metastasis or death from any cause in non-pCR patients
Time Frame
Disease free survival time for recurrence or death within 2 years of surgery
Secondary Outcome Measure Information:
Title
pCR rate
Description
Pathological complete response (pCR) rate of all patients
Time Frame
4 weeks after surgery
Title
major pathological response
Description
MPR was defined as the presence of viable tumor cells≤10% in the resected tumor specimen
Time Frame
4 weeks after surgery
Title
2-year DFS in pCR patients
Description
The time from the first day of surgery to the first occurrence of local or distant recurrence and metastasis or death from any cause in pCR patients
Time Frame
Disease free survival time for recurrence or death within 2 years of surgery
Title
R0 resection rate
Description
No vital tumor is presented at the proximal, distal, or circumferential resection margin, then it is considered R0 resection
Time Frame
4 weeks after surgery
Title
adverse events
Description
Safety will be evaluated for all treated patients using CTCAE V 5.0.
Time Frame
Up to 100 months
Title
overall survival
Description
The date of death of any causes since the date of randomization.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The patient volunteers to participate in the study, signs a consent form, has good compliance, and obeys the follow-up, and is willing and able to follow the protocol during the study; Histologically-confirmed squamous cell carcinoma; tumors of the esophagus are located in the thoracic cavity; Have not received systemic and local treatment for esophageal cancer; Pre-treatment staging as cT1b-3N1-3M0 or T3N0M0, American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition; Male or female, aged ≥18 and ≤75 years; The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score is 0 -1; R0 resection is expected; Adequate cardiac function. All patients should perform electrocardiogram (ECG), and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction >50%; Adequate respiratory function with forced expiratory volume in 1 second (FEV1) ≥ 1.2 L, FEV1% ≥ 50% and lung diffusing capacity for carbon monoxide (DLCO) ≥ 50% shown in pulmonary function tests; Adequate bone marrow function (white blood cells > 4×109/L, neutrophil > 1.5 ×109/L, hemoglobin > 90g/L, platelets > 100×109/L). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3× upper level of normal (ULN); Adequate liver function (total bilirubin <1.5× ULN, AST and ALT <2.5× ULN); Adequate renal function (glomerular filtration rate (GFR) >60 mL/min; serum creatinine (SCr) ≤120 μmol/L]; Fertile female subjects are required to have a negative serum or urine pregnancy test no later than 72 hours before starting the study drug administration, and to use effective contraception (such as an IUD, contraceptive pill, or condom) during the trial period and for at least 3 months after the last dose; For male subjects whose partners are women of reproductive age, effective contraception should be used during the trial period and within 3 months after the last dose. Exclusion Criteria: Unresectable factors, including those who are unresectable for tumor reasons or have surgical contraindications, or who refuse surgery; Patients with supraclavicular lymph node metastasis; Poor nutritional status, BMI<18.5Kg/m2; Patients could continue to be considered for enrollment if corrected with symptomatic nutritional support before enrollment and after assessment by the principal investigator Allergy to any drugs; Have received or are receiving any of the following treatments; a) any radiotherapy, chemotherapy or other antineoplastic drugs directed at the tumour; b) being treated with an immunosuppressive drug or systemic hormone for immunosuppression (at a dose of >10mg/ day of prednisone or equivalent) within 2 weeks before the first dose of the study drug; Inhaled or topical steroids and corticosteroid replacement at doses >10mg/ day of prednisone or equivalent were allowed in the absence of active autoimmune disease; c) received live attenuated vaccine within 4 weeks before the first dose of study drug; d) major surgery or severe trauma within 4 weeks before the first dose of study drug; Human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) active infection or known HIV seropositivity; including HBV or HCV surface antigen positive (RNA) Uncontrolled cardiac symptoms or diseases, including but not limited to: (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias without or poorly controlled after clinical intervention; Severe infection (CTCAE>2) occurred within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infectious complications; Prophylactic antibiotics were excluded if there was active pulmonary inflammation on chest imaging at baseline, if there were signs and symptoms of infection within 14 days before the first dose of the study drug, or if treatment with oral or intravenous antibiotics was required Participation in other drug clinical studies within 4 weeks before randomization; Patients with interstitial pneumonia or interstitial lung disease, or previous history of interstitial pneumonia or interstitial lung disease requiring hormone therapy, or other subjects with pulmonary fibrosis, organized pneumonia (such as bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia that may interfere with the judgment and treatment of immune related pulmonary toxicity, or subjects with active pneumonia or severe lung function damage revealed by CT during screening; Active pulmonary tuberculosis; Patients with any active autoimmune disease or history of autoimmune disease and possible recurrence [including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (patients who can be controlled only by hormone replacement therapy can be enrolled)]; Patients with skin diseases that do not require systemic treatment, such as leukoplakia, psoriasis, alopecia, patients with type I diabetes that can be controlled by insulin treatment, or patients with a history of asthma, but have completely relieved in childhood and do not need any intervention, can be enrolled; Asthma patients who needed bronchodilators for intervention could not be enrolled; Patients have previously received an anti-PD-1,PD-L1 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways; Other malignancies that had been diagnosed within 5 years before the first dose of a study drug were considered unless cancers with a low risk of metastasis or death (5-year survival rate, >90%), such as adequately treated basal-cell or squamous-cell skin cancer or carcinoma in situ of the cervix, were considered. Pregnant or lactating women; The investigators determined that there were other factors that might have led to the forced discontinuation of the study, such as other serious medical conditions (including mental illness) requiring co-treatment, alcohol, substance abuse, family or social factors, and factors that might have affected the safety or adherence of the subjects.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xufeng Guo, PH.D
Phone
189-300-96739
Email
shandagxf@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xufeng Guo, Ph.D
Phone
+8618930096739
Email
shandagxf@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Changqing Pan
Organizational Affiliation
the International Committee of Medical Journal Editors
Official's Role
Study Chair
Facility Information:
Facility Name
Shanghai chest hospital
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xufeng Guo, Ph.D
Phone
189-3009-6739
Email
shandagxf@126.com
First Name & Middle Initial & Last Name & Degree
Xufeng Guo, Ph.D

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is not a plan to make IPD available.
Citations:
PubMed Identifier
33789008
Citation
Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, Mendez G, Feliciano J, Motoyama S, Lievre A, Uronis H, Elimova E, Grootscholten C, Geboes K, Zafar S, Snow S, Ko AH, Feeney K, Schenker M, Kocon P, Zhang J, Zhu L, Lei M, Singh P, Kondo K, Cleary JM, Moehler M; CheckMate 577 Investigators. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125. Erratum In: N Engl J Med. 2023 Feb 16;388(7):672.
Results Reference
background
PubMed Identifier
34160577
Citation
Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J. Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial. JAMA Surg. 2021 Aug 1;156(8):721-729. doi: 10.1001/jamasurg.2021.2373. Erratum In: JAMA Surg. 2022 Sep 1;157(9):859.
Results Reference
result
PubMed Identifier
24419108
Citation
Oppedijk V, van der Gaast A, van Lanschot JJ, van Hagen P, van Os R, van Rij CM, van der Sangen MJ, Beukema JC, Rutten H, Spruit PH, Reinders JG, Richel DJ, van Berge Henegouwen MI, Hulshof MC. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014 Feb 10;32(5):385-91. doi: 10.1200/JCO.2013.51.2186. Epub 2014 Jan 13.
Results Reference
result

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Perioperative Tislelizumab Plus Chemotherapy for Resectable Thoracic Oesophageal Squamous Cell Carcinoma

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