Pharmacokinetics of Itraconazole in Pediatric Cancer Patients

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.

Study Overview

• Status: Completed
• Conditions: Pediatric, Cancer
• Intervention / Treatment: Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chongno-gu
    • Seoul, Chongno-gu, Korea, Republic of
      • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patients who are under chemotherapy, and receive itraconazole.

Exclusion Criteria:

1. 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㎡
2. Patients with hypersensitivity to azoles.
3. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
4. Pregnant or nursing women.
5. Psychiatric disorder that would preclude compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole	Drug: Itraconazole; pharmacokinetics; Other Names: Itraconazole(spranox)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: July 8, 2011
• First Submitted That Met QC Criteria: August 2, 2011
• First Posted (Estimate): August 3, 2011

Study Record Updates

• Last Update Posted (Estimate): November 19, 2013
• Last Update Submitted That Met QC Criteria: November 17, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: cancer; pediatric; invasive fungal disease; antifungal agent
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Hydroxyitraconazole
• Other Study ID Numbers: SNUCH-R-0804