Perioperative Tislelizumab Plus Chemotherapy for Resectable Thoracic Oesophageal Squamous Cell Carcinoma

NCT06056336 | Recruiting Phase 2 DMC

• 1 other identifier: IS23059
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Squamous Cell Carcinoma; Neoadjuvant Chemoimmunotherapy; Adjuvant Therapy

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

  Disease free survival time for recurrence or death within 2 years of surgery

Secondary Outcomes (6)

• pCR rate

  4 weeks after surgery

• major pathological response

  4 weeks after surgery

• 2-year DFS in pCR patients

  Disease free survival time for recurrence or death within 2 years of surgery

• R0 resection rate

  4 weeks after surgery

• adverse events

  Up to 100 months

Study Arms (1)

Adjuvant tislelizumab plus chemothearpy

EXPERIMENTAL

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

Interventions

Tislelizumab DRUG

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.

Also known as: Albumin-bound Paclitaxel, Carboplatin

Adjuvant tislelizumab plus chemothearpy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guo Xufeng: lead

Study Sites (1)

Shanghai chest hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Related Publications (3)

• 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. doi: 10.1056/NEJMx220014.

  PMID: 33789008 BACKGROUND

• 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.

  PMID: 34160577 RESULT

• 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.

  PMID: 24419108 RESULT

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

tislelizumab; Albumin-Bound Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, 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

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes

Study Officials

• Changqing Pan

  the International Committee of Medical Journal Editors

  STUDY CHAIR

Central Study Contacts

Xufeng Guo, PH.D

CONTACT

189-300-96739; shandagxf@126.com

Xufeng Guo, Ph.D

CONTACT

+8618930096739; shandagxf@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 10, 2023
• First Posted: September 28, 2023
• Study Start: September 7, 2023
• Primary Completion: September 30, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)