Pharmacokinetics of Itraconazole in Pediatric Cancer Patients

Study Overview
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Brief Summary
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This study investigated repeated-dose pharmacokinetics and safety of itraconazole and its active metabolite hydroxyitraconazole in pediatric cancer patients at risk for the development of invasive fungal disease.

Official Title
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Pharmacokinetics of Itraconazole in Pediatric Cancer Patients

Conditions
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Pediatric, Cancer

Intervention / Treatment
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* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients who are under chemotherapy, and receive itraconazole. Exclusion Criteria: Patients with significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases. Heart : fractional shortening < 30%, ejection fraction < 45% Liver : total bilirubin ≥ 2 x upper limit of normal (ULN) ; aminotransferase ≥ 3 x ULN Kidney : creatinine ≥ 2 x normal or GFR ≤ 60㎖/min/1.73㎡ Patients with hypersensitivity to azoles. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. Pregnant or nursing women. Psychiatric disorder that would preclude compliance.
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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Itraconazole<br> | Drug: Itraconazole<br>* pharmacokinetics<br>* Other names: Itraconazole(spranox);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate repeated-dose pharmacokinetics of itraconazole and its active metabolite hydroxyl itraconazole in pediatric cancer patients | Itraconazole administration 1) Oral for prophylaxis: 2mg/kg/dose,q12hr 2) IV for empirical therapy : After more than 2 days of oral prophylaxis, patients with persistent neutropenic fever / Induction : 5 mg/kg/dose, q12hr X 4 doses / Maintenance : 5 mg/kg/dose,q24hr Sampling 1) During oral : prior to the 5th dose 2) During IV : prior to the every induction and 1-5th maintenance doses, and 1, 2, 4, 8, 12, 24hr after the 3rd IV maintenance Analysis of drug concentrations : Plasma concentrations of itraconazole and hydroxyl-itraconazole are measured using HPLC. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess empirical antifungal efficacy and safety in pediatric cancer patients | Efficacy evaluation : Treatment is considered successful if all five of the following criteria are met : treatment of baseline fungal infection, absence of breakthrough fungal infection, survival for 7 days after completion, resolution of fever (<38°C for 48hrs) in neutropenia, and no premature discontinuation because of drug related toxicity or lack of efficacy. Safety evaluation : Laboratory are performed at the time of enrollment, twice weekly during therapy, and 1 week after the end of therapy. Drug-related toxicity was graded according to the NCI Common Toxicity Criteria (v4.0). | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, cancer, invasive fungal disease, antifungal agent