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

Sponsor

Ain Shams University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04863144

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Liver Diseases	Other: Blood samples

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 Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Feb 1, 2022

Outcome Measures

Primary Outcome Measures

plasma concentrations of paclitaxel [predose till 6 hours post infusion of paclitaxel]
determination of plasma concentration and pharmacokinetic analysis of paclitaxel
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
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

Secondary Outcome Measures

Probing CYP 3A4 activity [predose till 6 hours post infusion of paclitaxel]
metabolite ratio of 6-α-hydroxypaclitaxel/paclitaxel
Probing CYP 2C8 activity [predose till 6 hours post infusion of paclitaxel]
metabolite ratio of 3'-p-hydroxypaclitaxel/paclitaxel
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	El Demerdash Oncology Hospital	Cairo	Abbasia	Egypt	11865

Sponsors and Collaborators

Ain Shams University

Investigators

Study Director: Ahmed Nour-Eldin, Professor, Pharmacology Department - Faculty of Medicine - Ain Shams University
Study Director: Khaled Abdel-Aziz, MD, Oncology Department - Faculty of Medicine - Ain Shams University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ain Shams University

ClinicalTrials.gov Identifier:

NCT04863144

Other Study ID Numbers:

FMASU MD 8/2020

First Posted:

Apr 28, 2021

Last Update Posted:

Apr 28, 2021

Last Verified:

Apr 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Ain Shams University

Paclitaxel

Pharmacokinetics

Egypt

Additional relevant MeSH terms:

Liver Diseases

Study Results

No Results Posted as of Apr 28, 2021