Tirelizumab Combined With Chemotherapy in the Treatment of HER-2 Negative Locally Advanced Gastric Cancer

Safety Clinical Trial

Official title:

Clinical Efficacy and Safety of Tirelizumab Combined With Chemotherapy in the Treatment of HER-2 Negative Locally Advanced Resectable Gastric Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06284746
• Other study ID #: 301Qiaoz
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2023
• Est. completion date: July 30, 2025

Study information

• Verified date: February 2024
• Source: Chinese PLA General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study objectively analyzes the safety and survival evaluation of perioperative immunotherapy combined with chemotherapy in locally advanced gastric cancer patients through a prospective randomized controlled trial research method; By comparing the pathological response rate, disease-free survival rate, and incidence of adverse events between the combination therapy and chemotherapy alone group, we aim to verify the efficacy and safety of tirelizumab combined with SOX/XELOX chemotherapy in disease control of locally advanced gastric cancer patients, laying the foundation and providing a basis for large-scale multicenter clinical research.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: July 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• The subjects voluntarily joined this study and signed an informed consent form
• Locally advanced gastric or gastroesophageal junction adenocarcinoma confirmed by pathology or histology as HER-2 negative (cT2-4N+M0 Phase II-III)
• The primary lesion can be surgically removed, and the patient is willing to receive surgical treatment
• There are measurable solid tumors (efficacy evaluation standard: RECIST 1.1)
• Tumor evaluation should be conducted through CT scanning or MRI within 28 days before treatment
• ECOG score 0-1
• Life expectancy = 12 months.

Exclusion Criteria:

• Preoperative imaging examination indicates distant or peritoneal metastasis in patients
• Subjects with any known active autoimmune disease
• Serious cardiovascular disease
• The serum of the subjects tested positive for HIV
• Active hepatitis B (HbsAg positive and HBV-DNA = 10 ^ 3copies/mL) or active hepatitis C (HCV antibody positive and HCV-DNA positive, requiring antiviral treatment at the same time)
• Known subjects with previous allergies to macromolecular protein formulations/monoclonal antibody components, or other contraindications to immunotherapy or chemotherapy
• Have a history of alcohol, drug, or substance abuse
• Individuals with a clear history of neurological or mental disorders, such as epilepsy, dementia, and poor compliance

Related Conditions & MeSH terms

• Efficacy
• HER2 Negative
• Locally Advanced Gastric Carcinoma
• Safety
• Stomach Neoplasms

Intervention

Drug:
• Tirolizumab+SOX/XELOX
Tirolizumab combined with chemotherapy(SOX/XELOX) regimen. The SOX regimen consists of the drugs Tegilol (S-1) and Oxaliplatin. The XELOX regimen consists of the drugs oxaliplatin and capecitabine.
• SOX/XELOX
Simple chemotherapy regimen (SOX/XELOX regimen). The SOX regimen consists of the drugs Tegilol (S-1) and Oxaliplatin. The XELOX regimen consists of the drugs oxaliplatin and capecitabine.

Locations

Country	Name	City	State
China	General Surgery Institute, China PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Lin Chen

Country where clinical trial is conducted

China, 

References & Publications (10)

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Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015 May;3(5):436-43. doi: 10.1158/2326-6066.CIR-15-0064. — View Citation

Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, Jordan K; ESMO Guidelines Committee. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv119-iv142. doi: 10.1093/annonc/mdx225. No abstract available. Erratum In: Ann Oncol. 2018 Oct 1;29(Suppl 4):iv264-iv266. Ann Oncol. 2018 Oct;29 Suppl 4:iv264-iv266. — View Citation

Hogner A, Moehler M. Immunotherapy in Gastric Cancer. Curr Oncol. 2022 Mar 2;29(3):1559-1574. doi: 10.3390/curroncol29030131. — View Citation

Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. doi: 10.1016/S1470-2045(21)00692-6. Epub 2022 Jan 11. — View Citation

King GT, Sharma P, Davis SL, Jimeno A. Immune and autoimmune-related adverse events associated with immune checkpoint inhibitors in cancer therapy. Drugs Today (Barc). 2018 Feb;54(2):103-122. doi: 10.1358/dot.2018.54.2.2776626. — View Citation

Myers G. Immune-related adverse events of immune checkpoint inhibitors: a brief review. Curr Oncol. 2018 Oct;25(5):342-347. doi: 10.3747/co.25.4235. Epub 2018 Oct 31. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caa — View Citation

Xu J, Jiang H, Pan Y, et al. LBA53 Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): First results of a randomized, double-blind, phase III study. Ann Oncol. 2021;32:S1331. doi:10.1016/j.annonc.2021.08.2133

Zheng R, Zhang S, Zeng H, et al. Cancer incidence and mortality in China, 2016. J Natl Cancer Cent. 2022;2(1):1-9. doi:10.1016/j.jncc.2022.02.002

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response (pCR)	After neoadjuvant therapy, there were no residual surviving tumor cells in the tumor bed during the pathological remission assessment of postoperative specimens.	Less than 20 months
Primary	Objective Response Rate(ORR)	The proportion of patients whose tumor volume has shrunk to a predetermined value and can maintain the minimum time limit requirement is the sum of complete response (CR) and partial response (PR) ratios, with ORR=CR+PR.	Less than 20 months
Secondary	Disease-free survival(DFS)	Time from randomization to disease recurrence or (for any reason) death.	Less than 20 months
Secondary	Overall survival(OS)	Time from randomization to death (for any reason)	Less than 20 months
Secondary	Major Pathologic Response(MPR)	After preoperative treatment, the number of surviving tumors decreases below the threshold that can affect clinical prognosis.	Less than 20 months
Secondary	The incidence of adverse events during treatment	Including adverse reactions related to immunotherapy and postoperative complications. Reflecting safety and tolerability.	Less than 20 months