Study on Umorestat Hydrogen Sulfate Capsule in Patients With Locally Advanced/Metastatic Pancreatic Cancer

• Conditions: Pancreatic Cancer; Gene Polymorphisms; Pharmacokinetics
• Interventions: Genetic: Genotyping

• Registration Number: NCT05329597
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

Based on the tolerability, safety and pharmacokinetics phase I/II clinical trials of ulimostat hydrochloride capsules (LH011) combined with gemcitabine hydrochloride (GEM) in locally advanced/metastatic pancreatic cancer patients, to determine pharmacokinetics, the biotransformation pathway and metabolite profile of ulimostat in patients with locally advanced/metastatic pancreatic cancer.

Detailed Description

This study is a research on the pharmacokinetics and gene polymorphisms of ulimostat hydrochloride capsules in patients with locally advanced/metastatic pancreatic cancer. Aims to collect the "Phase I/II clinical trials of the tolerability, safety and pharmacokinetics of ulimostat capsules (LH011) combined with gemcitabine hydrochloride (GEM) in patients with locally advanced/metastatic pancreatic cancer" patient's peripheral blood sample to determine the structure of the metabolites of ulimostat in the biological samples and trough concentration and genotyping tests were performed on patients to investigate the correlation between gene polymorphisms of metabolic enzymes, transporters, target protein uPA and proteins expressed in upstream and downstream signaling pathways and blood drug concentration, efficacy, safety and tolerance of ulimostat.

Study Timeline

• Study Start: 2020-06-24
• Study First Submitted: 2021-12-21
• Status Verified: 2022-04
• Study First Submitted QC: 2022-04-07
• Last Update Submitted: 2022-04-07
• Study First Posted: 2022-04-15
• Last Update Posted: 2022-04-15
• Primary Completion: 2022-06
• Study Completion: 2022-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

• Successfully enrolled in a Phase I/II clinical study on the tolerability, safety and pharmacokinetics of Umorestat hydrogen Sulfate capsule (LH011) combined with gemcitabine hydrochloride (GEM) for patients with locally advanced/metastatic pancreatic cancer.
• Fully understand the purpose and requirements of this study and sign a written informed consent.
• Willing to provide blood samples.

Exclusion Criteria

• Suffering from inflammatory bowel disease.
• The researcher considers it unsuitable to participate in this study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
100mg	Genotyping	After 15 consecutive days of takeing 100mg Umorestat capsule of each participant, 2 mL of peripheral venous blood is collected at 3 h, 8 h and 24 h (D16) on the 15th day into the vacuum blood collection tube via EDTA anticoagulation for genotyping and metabolite determination.
200mg	Genotyping	After 15 consecutive days of takeing 200mg Umorestat capsule of each participant, 2 mL of peripheral venous blood is collected at 3 h, 8 h and 24 h (D16) on the 15th day into the vacuum blood collection tube via EDTA anticoagulation for genotyping and metabolite determination.
600mg	Genotyping	After 15 consecutive days of takeing 600mg Umorestat capsule of each participant, 2 mL of peripheral venous blood is collected at 3 h, 8 h and 24 h (D16) on the 15th day into the vacuum blood collection tube via EDTA anticoagulation for genotyping and metabolite determination.
400mg	Genotyping	After 15 consecutive days of takeing 400mg Umorestat capsule of each participant, 2 mL of peripheral venous blood is collected at 3 h, 8 h and 24 h (D16) on the 15th day into the vacuum blood collection tube via EDTA anticoagulation for genotyping and metabolite determination.

Primary Outcome Measures

Name	Time	Method
Metabolite profile	After sampling blood samples (approximately 2 weeks)	Determine the drug metabolite profile: Serum samples were detected by ultra-high pergormance liquid tandem chromatography quadrupole time of flight mass spectrometry(LC-MS). Differential metabolites were screened by principal component analysis(PCA), orthogonal projections to latent structures-discriminant analysis(OPLS-DA) and Student's t-test. Then the hierarchical clustering analysis(HCA) was carried out for the screened differential metabolites.
Genotyping	After sampling blood samples (approximately 2 weeks)	To determine the relationship between genotyping and drug exposure, efficacy and safety: Employs PCR to amplify the regions of the genome containing each SNP, then use MassARRAY to detect mass differences between fragments differing by a single base. Use genotyping test results to do correlation analysis with drug concentration, safety results, and efficacy results to determine the relationship between different types of gene locus mutations and drug concentration, efficacy, and adverse reactions.

Trial Locations

Locations (1)

Sun Yat-Sen Memorial Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China