NCT00697437

Effect of Ketoconazole Inhibition of CYP3A on Urinary Excretion of Docetaxel

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Primary Objective: * To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine. Secondary Objective: * To compare the metabolite ratios of the major metabolites of docetaxel in the presence and absence of CYP3A inhibition.

Detailed description

Introduction: This is a follow-up protocol to an earlier study entitled "A phase I study of docetaxel with ketoconazole modulation in solid tumors" (PH14/01) which showed 2-fold reduction in docetaxel clearance and a clear correlation with renal function. Aims: The aim of this study is to confirm that ketoconazole inhibition of CYP3A activity changes the urinary excretion profile of docetaxel. Methodology: This is a single-centre, crossover study. Ten patients (calculated sample size =5, α=0.05, β=0.8, difference in means=5%, within group standard deviation=3) will be accrued and randomly assigned to receive docetaxel at either 75mg/m2 q3w x 1 dose or 70mg q3w x 1 dose with ketoconazole 200mg bid x q3d at cycle 1 of chemotherapy. This will be followed by a 20-day washout period before receiving the other regimen of docetaxel at cycle 2. Blood samples of 5mls each will be drawn at times 0, 0.5h, 1h, 1.5h, 3h, 4h, 6h and 24h after the onset of docetaxel infusion for pharmacokinetics analysis. A 24-hour urine collection commencing on the same day as docetaxel infusion will be required of the patients. All urine over the next 24 hours must be collected and returned to the study coordinator on Day 2 of each study cycle for docetaxel analysis and creatinine clearance determination. The amount of docetaxel excreted by each patient with and without ketoconazole modulation will be determined by a LCMSMS method and compared. Clinical Relevance: This is to ensure the safe advocation of a dose-sparing strategy established in an earlier study for the costly agent docetaxel by confirming if changes in excretion profile occurs once its major route of hepatic metabolism is blocked.

Conditions

• Solid Tumors

Interventions

Type	Name	Description
DRUG	Docetaxel	70mg q3wx 1 dose
DRUG	Ketoconazole	6 doses of oral ketoconazole 200mg bid starting 2 days before, and with 1 dose to be completed after, docetaxel infusion

Timeline

• Start date: 2006-10-01
• Primary completion: 2013-10-01
• Completion: 2013-10-01
• First posted: 2008-06-13
• Last updated: 2013-12-10

Locations

1 site across 1 country: Singapore