Metabolomic and Lipidomic Analysis Predicts Immunotherapy-related Adverse Events in Gastric Cancer Patients

NCT06915389 | Recruiting DMC

• 1 other identifier: KY-2025-02
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study comprehensively examines metabolic and lipidomic dynamics in gastric cancer patients initiating PD-1/PD-L1 inhibitor therapy, employing a longitudinal design with pre- and post-treatment patients. The primary objectives include identifying irAE-associated metabolic and lipid biomarkers, developing predictive risk models, and evaluating the prognostic value of these molecular profiles. The findings are expected to contribute significantly to personalized treatment strategies and improved clinical decision-making in immunooncology.

Conditions

Gastric Cancer; Immunotherapy; Adverse Event; Metabonomics; Lipidomics

Keywords

Immune-related adverse events (irAEs); PD-1/PD-L1 inhibitors; Gastric cancer; Biomarkers; Metabolic; Lipidomic

Outcome Measures

Primary Outcomes (3)

• Incidence of immune-related adverse events

  * For gastric cancer patients receiving immunotherapy for the first time, immune-related adverse events should be monitored during treatment, with a follow-up period of 1 year. * The immune checkpoint inhibitors include pembrolizumab, nivolumab, sintilimab, tislelizumab, sugemalimab and camrelizumab. * NCCN Guidelines for Management of Immunotherapy-Related Toxicity are adopted as the gold standard for assessing immune-related adverse events. * The severity of immune-related adverse events was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

  1 year

• Changes in Plasma Metabolite Levels

  * A comprehensive metabolomic profiling of plasma in treatment-naïve gastric cancer patients undergoing immunotherapy: Investigating metabolic disparities between responders with immune-related adverse events and those without. * The measurement methods include gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). * The measured metabolites include amino acids, fatty acids, glucose, lactate, nucleotides, organic acids, vitamins and small-molecule metabolites. * All metabolomic markers in plasma will be reported as relative quantitative values in arbitrary units. * Baseline plasma samples were collected from all patients prior to immunotherapy, and follow-up samples were obtained every 2 treatment cycles until 1 year after treatment initiation.

  1 year

• Changes in Plasma Lipid Levels

  * Comprehensive lipidomic profiling of plasma from gastric cancer patients undergoing initial immunotherapy was performed to investigate differential plasma lipid signatures between those who developed immune-related adverse events and those who did not. * The measurement methods include gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). * The measured lipids include triglycerides, cholesterol, phospholipids, fatty acids, ceramides, steroids, fatty acid derivatives, and other sphingolipids. * All plasma lipidomic markers will be reported as relative quantitative values in arbitrary units. * Baseline plasma samples were collected from all patients prior to immunotherapy, with subsequent samples obtained every 2 treatment cycles until 1 year of therapy.

  1 year

Secondary Outcomes (2)

• Develop a predictive model for immune-related adverse events

  2 years

• Investigating the correlation between metabolomic and lipidomic profiles and patient outcomes to inform evidence-based clinical decision-making.

  2 years

Study Arms (2)

Immune-related adverse events（irAEs）group

Integrated metabolomic and lipidomic profiling was conducted to delineate the differential metabolic signatures and lipidomic alterations prior to PD-1/PD-L1 inhibitor therapy initiation and throughout the progression of immune-related adverse events (irAEs)

Non-Immune-related adverse events (Non-irAEs) group

Integrated metabolomic and lipidomic profiling was conducted to delineate the differential metabolic signatures and lipidomic alterations prior to PD-1/PD-L1 inhibitor therapy initiation and throughout the progression of immune-related adverse events (irAEs)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All the research subjects were patients with gastric cancer who were aged ≥ 18 years, had ECOG score ranging from 0 to 2, were confirmed by pathology, and received either anti-PD-L1/anti-PD-1 monotherapy or combination chemotherapy, with an expected survival period of ≥ 3 months

You may qualify if:

• Age≥ 18 years
• ECOG PS 0-2
• Gastric cancer diagnosed by histology or cytology
• Untreatment with PD-1/PD-L1 inhibitors
• Expected survival≥3 months
• Exhibits a favorable adherence to treatment and follow-up,demonstrates compliance with the research protocol, and willingly signs the informed consent form.

You may not qualify if:

• Unable to obtain an organization or due to insufficient organizational material, unable to diagnose gastric cancer
• Refusal to receive PD-1/PD-L1 inhibitor treatment
• Baseline (before immunotherapy) plasma samples are unavailable
• Combined with autoimmune diseases
• Baseline (before immunotherapy) there are severe diseases in the heart, lungs, thyroid gland and other organs
• Baseline (before immunotherapy) there are severe abnormalities in liver and kidney functions, pancreatic enzymes and other indicators

Sponsors & Collaborators

• Qinghai Red Cross Hospital: lead

Study Sites (1)

Qinghai Red Cross Hospital

Xining, Qinghai, 810000, China

RECRUITING

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 Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: April 8, 2025
• Study Start: February 22, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 8, 2025

Record last verified: 2025-02

Locations

CN (1)