Pharmacokinetics of Paclitaxel in Correlation With Adverse Events in Cancer Patients With and Without Liver Impairment

Liver Diseases Clinical Trial

Official title:

Effect of CYP3A4 and CYP2C8 Activity on Pharmacokinetics of Paclitaxel, Correlation With Adverse Events in Cancer Patients With and Without Liver Impairment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04863144
• Other study ID #: FMASU MD 8/2020
• Status: Recruiting
• Start date: August 1, 2020
• Est. completion date: February 1, 2022

Study information

• Verified date: April 2021
• Source: Ain Shams University
• Contact: Ahmed M Mohamed, Master
• Phone: 01126109080
• Email: dr_ahmed_mostafa[@]med.asu.edu.eg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study aims to assess the pharmacokinetics of paclitaxel and its two major metabolites in patients with normal and impaired liver functions.

Description:

population pharmacokinetic study in patients with normal or impaired liver functions, receiving paclitaxel for cancer treatment. 40 Patients with histologically confirmed solid tumors will be enrolled in the study: - 20 patients have normal liver functions as defined by transaminase < 2.6 x ULN and bilirubin values < 1.26 x ULN. - 20 patients with liver impairment as defined by transaminase 2.6 - 10 x ULN and bilirubin values 1.26 - 5 x ULN.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients with histologically proven non haematopoietic malignancy (ovarian, breast and lung cancer).
• Age between 18 and 70 years
• At least a 4-week interval between the last dose of previous chemotherapy protocol and registration (6 weeks in case of treatment with carboplatin).
• Glomerular filtration rate > 60 ml/min
• An Eastern Cooperative Oncology Group performance status 0-2, a life expectancy of > 12 weeks, adequate bone marrow function [absolute neutrophil count (ANC) = 1 X 109 and platelets = 100 X 109]
• Patient accessible for treatment and follow-up and written informed consent.

Exclusion Criteria:

• Prior treatment with paclitaxel or other taxanes.
• Pre-existing motor or sensory neurotoxicity > grade 2 according to World Health Organization (WHO) criteria.
• Active infection or other serious underlying medical condition (including prior allergic reactions to Paclitaxel or the drug's constituents), dementia or significantly altered mental status, symptomatic brain or liver metastases, history of atrial or ventricular arrhythmias or congestive heart failure even if medically controlled, history of clinical and electrocardiographically documented myocardial infarction.
• Simultaneous use of any medication, dietary supplements, or other compounds known to inhibit affect the pharmacokinetics of paclitaxel.
• Patients with difficult blood sampling.

Related Conditions & MeSH terms

• Liver Diseases

Intervention

Other:
• Blood samples
Plasma concentrations of paclitaxel and its metabolites will be obtained during the first treatment cycle. The samples for paclitaxel analysis will be collected in ethylenediamine tetraacetic acid tubes at 7-time points: just before infusion, in the middle of the infusion, at the end of infusion, at 1, 2, 4 and 6 hours post-infusion.

Locations

Country	Name	City	State
Egypt	El Demerdash Oncology Hospital	Cairo	Abbasia

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma concentrations of paclitaxel	determination of plasma concentration and pharmacokinetic analysis of paclitaxel	predose till 6 hours post infusion of paclitaxel
Primary	plasma concentrations of 6-a-hydroxypaclitaxel	determination of plasma concentration and pharmacokinetic analysis of 6-a-hydroxypaclitaxel	predose till 6 hours post infusion of paclitaxel
Primary	plasma concentrations of 3'-p-hydroxypaclitaxel	determination of plasma concentration and pharmacokinetic analysis of 3'-p-hydroxypaclitaxel	predose till 6 hours post infusion of paclitaxel
Secondary	Probing CYP 3A4 activity	metabolite ratio of 6-a-hydroxypaclitaxel/paclitaxel	predose till 6 hours post infusion of paclitaxel
Secondary	Probing CYP 2C8 activity	metabolite ratio of 3'-p-hydroxypaclitaxel/paclitaxel	predose till 6 hours post infusion of paclitaxel
Secondary	Incidence of adverse effects	Complete blood count, liver functions and neuropathy evaluation (according to Common Terminology Criteria for Adverse Events (CTCAE), version 5) will be assessed	baseline ( before first dose) till 100 days after the first dose