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

• Conditions: Liver Diseases

• Registration Number: NCT04863144
• Lead Sponsor: Ain Shams University

Brief Summary

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

Detailed 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.

Study Timeline

• Study Start: 2020-08-01
• Status Verified: 2021-04
• Study First Submitted: 2021-04-21
• Study First Submitted QC: 2021-04-27
• Last Update Submitted: 2021-04-27
• Study First Posted: 2021-04-28
• Last Update Posted: 2021-04-28
• Primary Completion: 2021-12-01
• Study Completion: 2022-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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.

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
plasma concentrations of paclitaxel	predose till 6 hours post infusion of paclitaxel	determination of plasma concentration and pharmacokinetic analysis of paclitaxel
plasma concentrations of 3'-p-hydroxypaclitaxel	predose till 6 hours post infusion of paclitaxel	determination of plasma concentration and pharmacokinetic analysis of 3'-p-hydroxypaclitaxel
plasma concentrations of 6-α-hydroxypaclitaxel	predose till 6 hours post infusion of paclitaxel	determination of plasma concentration and pharmacokinetic analysis of 6-α-hydroxypaclitaxel

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse effects	baseline ( before first dose) till 100 days after the first dose	Complete blood count, liver functions and neuropathy evaluation (according to Common Terminology Criteria for Adverse Events (CTCAE), version 5) will be assessed
Probing CYP 2C8 activity	predose till 6 hours post infusion of paclitaxel	metabolite ratio of 3'-p-hydroxypaclitaxel/paclitaxel
Probing CYP 3A4 activity	predose till 6 hours post infusion of paclitaxel	metabolite ratio of 6-α-hydroxypaclitaxel/paclitaxel

Trial Locations

Locations (1)

El Demerdash Oncology Hospital; 🇪🇬 Cairo, Abbasia, Egypt