Perioperative Tislelizumab Plus Chemotherapy for Resectable Thoracic Oesophageal Squamous Cell Carcinoma

• ClinicalTrials.gov Identifier: NCT06056336
• Recruitment Status: Recruiting
• First Posted: September 28, 2023
• Last Update Posted: September 28, 2023
• Sponsor: Guo Xufeng
• Information provided by (Responsible Party): Guo Xufeng, Shanghai Chest Hospital

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.

Condition or disease	Intervention/treatment	Phase
Esophageal Squamous Cell Carcinoma; Neoadjuvant Chemoimmunotherapy; Adjuvant Therapy	Drug: Tislelizumab	Phase 2

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 73 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: September 7, 2023
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: December 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adjuvant tislelizumab plus chemothearpy; 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.	Drug: Tislelizumab; 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.; Other Names: Albumin-bound Paclitaxel; Carboplatin

Outcome Measures

Primary Outcome Measures :

1. 2-year disease-free survival in non-pCR patients [ Time Frame: Disease free survival time for recurrence or death within 2 years of surgery ]
   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 :

1. pCR rate [ Time Frame: 4 weeks after surgery ]
   Pathological complete response (pCR) rate of all patients
2. major pathological response [ Time Frame: 4 weeks after surgery ]
   MPR was defined as the presence of viable tumor cells≤10% in the resected tumor specimen
3. 2-year DFS in pCR patients [ Time Frame: Disease free survival time for recurrence or death within 2 years of surgery ]
   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
4. R0 resection rate [ Time Frame: 4 weeks after surgery ]
   No vital tumor is presented at the proximal, distal, or circumferential resection margin, then it is considered R0 resection
5. adverse events [ Time Frame: Up to 100 months ]
   Safety will be evaluated for all treated patients using CTCAE V 5.0.
6. overall survival [ Time Frame: Up to 5 years ]
   The date of death of any causes since the date of randomization.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. 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;
2. Histologically-confirmed squamous cell carcinoma; tumors of the esophagus are located in the thoracic cavity;
3. Have not received systemic and local treatment for esophageal cancer;
4. Pre-treatment staging as cT1b-3N1-3M0 or T3N0M0, American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition;
5. Male or female, aged ≥18 and ≤75 years;
6. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score is 0 -1;
7. R0 resection is expected;
8. 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%;
9. 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;
10. 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);
11. Adequate liver function (total bilirubin <1.5× ULN, AST and ALT <2.5× ULN);
12. Adequate renal function (glomerular filtration rate (GFR) >60 mL/min; serum creatinine (SCr) ≤120 μmol/L];
13. 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:

1. Unresectable factors, including those who are unresectable for tumor reasons or have surgical contraindications, or who refuse surgery;
2. Patients with supraclavicular lymph node metastasis;
3. 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
4. Allergy to any drugs;
5. 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;
6. 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)
7. 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;
8. 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
9. Participation in other drug clinical studies within 4 weeks before randomization;
10. 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;
11. 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;
12. 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.
13. Pregnant or lactating women;
14. 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.

Contacts and Locations

Contacts

Contact: Xufeng Guo, PH.D; 189-300-96739; shandagxf@126.com

Contact: Xufeng Guo, Ph.D; +8618930096739; shandagxf@126.com

Locations

China, Shanghai

Shanghai chest hospital; Recruiting

Shanghai, Shanghai, China

Contact: Xufeng Guo, Ph.D 189-3009-6739 shandagxf@126.com

Principal Investigator: Xufeng Guo, Ph.D

Sponsors and Collaborators

Guo Xufeng

Investigators

• Study Chair: Changqing Pan; the International Committee of Medical Journal Editors

  Study Documents (Full-Text)

Documents provided by Guo Xufeng, Shanghai Chest Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] September 6, 2023

More Information

Publications of Results:

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.

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.

Other Publications:

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.

• Responsible Party: Guo Xufeng, Principal Investigator, Shanghai Chest Hospital
• ClinicalTrials.gov Identifier: NCT06056336
• Other Study ID Numbers: IS23059
• First Posted: September 28, 2023
• Last Update Posted: September 28, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: There is not a plan to make IPD available.

• 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

Keywords provided by Guo Xufeng, Shanghai Chest Hospital:

esophageal Squamous Cell Carcinoma; neoadjuvant chemotherapy; neoadjuvant immunotherapy; adjuvant therapy

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Paclitaxel; Carboplatin; Tislelizumab; Albumin-Bound Paclitaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological