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

NCT07511894 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NFEC-2026-187
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Cancer

Keywords

Gastric Cancer; Immunotherapy; Beta-Blockers

Outcome Measures

Primary Outcomes (1)

• Pathological response of TRG3

  Pathological response is assessed on the surgical resection specimen obtained approximately 1 week after completion of neoadjuvant therapy. Tumor regression grade (TRG) is evaluated according to the American Joint Committee on Cancer (AJCC) 8th edition criteria. Pathological non-response is defined as TRG 3, which corresponds to \>50% viable tumor cells remaining in the tumor bed. The primary efficacy endpoint is the pathological response rate, defined as the proportion of patients achieving TRG 0-2 (≤50% residual viable tumor cells). The incidence of TRG 3 (non-response) will be reported descriptively. All pathological evaluations are performed by an experienced gastrointestinal pathologist.

  From completion of neoadjuvant therapy to surgical resection; assessed on postoperative pathological specimen approximately 1 week after surgery, up to 4 months after study treatment initiation.

Secondary Outcomes (4)

• 3-year overall survival (OS)

  From the start of study treatment (first dose of neoadjuvant immunotherapy) to death from any cause, assessed up to 36 months post-surgery. The 3-year OS rate is measured at 36 months after surgery.

• 3-year progression-free survival (PFS)

  From start of study treatment to the first documented disease progression or death, assessed up to 36 months post-surgery. The 3-year PFS rate is measured at 36 months after surgery.

• Correlation with immunotherapy-related biomarkers

  Pre-treatment tumor biopsy at baseline; blood samples at baseline and before surgery (approximately 4 months); post-treatment tumor tissue from surgical resection specimen (approximately 1 week after surgery).

• Pathological response of MPR

  From completion of neoadjuvant therapy to surgical resection; assessed on postoperative pathological specimen approximately 1 week after surgery, up to 4 months after study treatment initiation.

Other Outcomes (1)

• Incidence of treatment-related adverse events

  From the time of informed consent through 30 days after the last dose of the study drug

Study Arms (1)

Experimental group

EXPERIMENTAL

Subjects in the experimental group will start taking metoprolol succinate extended-release tablets 47.5 mg (one tablet) once daily, starting from Day 1 of the first cycle of preoperative neoadjuvant immunotherapy, and continue until the day before surgery.

Drug: Experimental Group

Interventions

Experimental Group DRUG

Subjects in the experimental group will start taking metoprolol succinate extended-release tablets 47.5 mg (one tablet) once daily, starting from Day 1 of the first cycle of preoperative neoadjuvant immunotherapy, and continue until the day before surgery.

Experimental group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Xinhua Chen, Ph.D

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xinhua Chen, Ph.D

CONTACT

86-15626452302; xinhuachen03@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Given the single-arm design with no requirement for inter-group comparison, blinding for pathologists, radiologists, and follow-up evaluators will not be implemented.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After signing the informed consent form, patients meeting the inclusion criteria will be enrolled. All enrolled subjects will receive a unified treatment regimen: Basic Treatment: 4 cycles of preoperative immunotherapy combined with chemotherapy (anti-PD-1 antibody + XELOX/SOX/Capoex regimen, every 3 weeks \[Q3W\]). Intervention: During the 4 cycles, subjects will take a fixed daily dose of metoprolol succinate extended-release tablets (47.5 mg), continuing until the day before surgery.

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 6, 2026
• Study Start: May 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)