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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Study on Pharmacokinetics and Gene Polymorphism of Umorestat Hydrogen Sulfate Capsule in Patients With Locally Advanced/Metastatic Pancreatic Cancer

Conditions
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Pharmacokinetics, Pancreatic Cancer, Gene Polymorphisms

Intervention / Treatment
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* Genetic: Genotyping


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 100mg<br>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. | Genetic: Genotyping<br>* Genotyping is performed using the subjects' blood cells<br>|
| 200mg<br>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. | Genetic: Genotyping<br>* Genotyping is performed using the subjects' blood cells<br>|
| 400mg<br>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. | Genetic: Genotyping<br>* Genotyping is performed using the subjects' blood cells<br>|
| 600mg<br>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. | Genetic: Genotyping<br>* Genotyping is performed using the subjects' blood cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolite profile | 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. | After sampling blood samples (approximately 2 weeks) | 
| Genotyping | 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. | After sampling blood samples (approximately 2 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, gene polymorphisms, pancreatic cancer