Clinical trial NCT04863144: Pharmacokinetics of Paclitaxel in Correlation With Adverse Events in Cancer Patients With and Without Liver Impairment
Official title: Effect of CYP3A4 and CYP2C8 Activity on Pharmacokinetics of Paclitaxel, Correlation With Adverse Events in Cancer Patients With and Without Liver Impairment
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Diseases
Keywords: Paclitaxel
Pharmacokinetics
Egypt
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2021-04-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 40 Patients with histologically confirmed solid tumors and are going to receive paclitaxel

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.

Eligibility criteria: 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.

Primary outcomes:
measure: plasma concentrations of paclitaxel
timeFrame: predose till 6 hours post infusion of paclitaxel
measure: plasma concentrations of 6-α-hydroxypaclitaxel
timeFrame: predose till 6 hours post infusion of paclitaxel
measure: plasma concentrations of 3'-p-hydroxypaclitaxel
timeFrame: predose till 6 hours post infusion of paclitaxel
Secondary outcomes:
measure: Probing CYP 3A4 activity
timeFrame: predose till 6 hours post infusion of paclitaxel
measure: Probing CYP 2C8 activity
timeFrame: predose till 6 hours post infusion of paclitaxel
measure: Incidence of adverse effects
timeFrame: baseline ( before first dose) till 100 days after the first dose
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: El Demerdash Oncology Hospital
state: Abbasia
Study officials:
affiliation: Pharmacology Department - Faculty of Medicine - Ain Shams University
name: Ahmed Nour-Eldin, Professor
role: STUDY_DIRECTOR
affiliation: Oncology Department - Faculty of Medicine - Ain Shams University
name: Khaled Abdel-Aziz, MD
role: STUDY_DIRECTOR
References: