Clinical Research Directory

Beta-Blockers on the Efficacy of Neoadjuvant Immunotherapy for Gastric Cancer

Sponsor: Nanfang Hospital, Southern Medical University

Summary

Study Population:Patients with locally advanced gastric cancer complicated by hypertension, who are scheduled to undergo laparoscopic gastric cancer resection after receiving preoperative immunotherapy. Primary Objective: To investigate the impact of combined beta-blocker use on the efficacy of immunotherapy in patients with locally advanced gastric cancer. Secondary Objective: To investigate the impact of combined beta-blocker use on the incidence of immune-related adverse events. Study Groups:This study does not include a parallel control group; it enrolls only a single study group. Study Design:This is a single-arm, exploratory clinical study. Study Duration:2026 - 2029 Sample Size: Single-arm, exploratory trial, planned enrollment of 33 cases. Inclusion Criteria: * Voluntarily sign the informed consent form; * Aged 18-75 years; * ECOG performance status 0-1; * Either sex; * Patients with a standardized histopathological diagnosis of gastric adenocarcinoma from the primary gastric lesion via endoscopic biopsy, according to the 15th edition of the Japanese Classification of Gastric Carcinoma (2017); * Patients judged by the treating physician to require preoperative immune checkpoint inhibitor therapy, followed by potentially curative gastrectomy; * Meet the diagnostic criteria for hypertension according to the 2023 Chinese Guidelines for the Management of Hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or a previous diagnosis of uncontrolled hypertension), with an indication for beta-blocker use; * Deemed by a specialist to have no contraindications for beta-blocker use and can use beta-blockers for antihypertensive therapy. Exclusion Criteria * HER2-positive or microsatellite instability-high (MSI-H)/dMMR gastric cancer confirmed by immunohistochemistry; * Active autoimmune disease requiring continuous immunosuppressive therapy or history of transplantation; * Currently receiving systemic immunosuppressive medication: If a patient is currently using corticosteroids, the corticosteroid dose must be ≤ equivalent of prednisone 10 mg daily; * History of (non-infectious) pneumonitis/interstitial lung disease requiring treatment; * Concurrent infection with human immunodeficiency virus (HIV); * Pregnant or breastfeeding women; * History of psychiatric disorders; * Concurrent other malignancies or severe organ dysfunction; * Presence of contraindications for beta-blocker use (e.g., severe bradycardia, uncontrolled depression, unstable angina, uncontrolled heart failure (Class III or IV), hypotension (systolic blood pressure \<100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, etc.); * Refractory hypertension; * Judged by the investigator as not meeting the inclusion criteria for this study. Effectiveness Analysis Primary Endpoint: Proportion of patients with Tumor Regression Grade (TRG) \< 3 (AJCC criteria). Secondary Endpoints: 3-year overall survival (OS), 3-year progression-free survival (PFS); correlation with immunotherapy-related biomarkers (e.g., PD-L1 expression, cortisol, adrenocorticotropic hormone, tumor tissue ADRB1 expression, tumor tissue RNA sequencing, tumor immune microenvironment); treatment compliance (immunotherapy completion rate, surgery delay rate). Safety Analysis:Incidence and severity of adverse events. Statistical Analysis:This is an exploratory, single-arm, uncontrolled study. The pathological response rate is the primary evaluation indicator, with a planned enrollment of 33 cases. The sample size was calculated based on the single-sample rate estimation method. Referring to similar exploratory immunotherapy combination studies and considering clinical practice, the anticipated pathological response rate is 80%. Using a two-sided α=0.05 (95% confidence level) and the Clopper-Pearson exact method, the two-sided 95% confidence interval for 33 samples is \[0.625, 0.918\], with an interval width of 0.294, which meets the core objective of preliminarily verifying the efficacy trend of the "standard immunotherapy + beta-blocker" regimen. A 10% dropout rate is also accounted for, balancing recruitment feasibility with basic statistical estimation precision. Descriptive statistical analysis will be used to calculate point estimates and 95% confidence intervals for primary and secondary endpoints. Survival analysis will use the Kaplan-Meier method to plot 3-year OS and PFS curves. Follow-up:Follow-up will be conducted at 1, 3, 6, 9, 12, 15, 18, 21, 24, 30, and 36 months post-surgery.

Official title: Efficacy and Safety of Beta-Blockers Combined With Neoadjuvant Immunotherapy for Locally Advanced Gastric Cancer: an Open-lable, Single-arm Study

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