Effect of Ketoconazole Inhibition of CYP3A on Urinary Excretion of Docetaxel

NCT00697437 | Completed Phase 2 DMC

• 1 other identifier: PK01/01/06
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• To confirm if ketoconazole inhibition of CYP3A activity affects fractional excretion of docetaxel in the urine.

  9 weeks

Secondary Outcomes (1)

• To compare the metabolite ratios of the major metabolites of docetaxel in the presence and absence of CYP3A inhibition.

  12 weeks

Study Arms (2)

docetaxel only

EXPERIMENTAL

Drug: Docetaxel

docetaxel with ketoconazole

EXPERIMENTAL

Drug: Docetaxel; Drug: Ketoconazole

Interventions

Docetaxel DRUG

70mg q3wx 1 dose

docetaxel only; docetaxel with ketoconazole

Ketoconazole DRUG

6 doses of oral ketoconazole 200mg bid starting 2 days before, and with 1 dose to be completed after, docetaxel infusion

docetaxel with ketoconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which docetaxel is indicated.
• Patients must have measurable or evaluable disease.
• With the exception of alopecia, fatigue, nausea and asthenia, patients must have resolution of all acute toxic effects of any prior surgery' radiotherapy or chemotherapy to National Cancer Institute (NCI) Common Toxicity Criteria version 3.0 grade \< 1.
• Patients must have ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
• Patients must have a life expectancy of greater than 3 months.
• Patients must have normal renal and marrow function as defined below:
• leukocytes ≥ 3,000/μl
• absolute neutrophil count ≥ 1,500/μl
• platelets ≥ 100,000/μl
• haemoglobin ≥ 7g/dL
• creatinine ≤ 1.5 X institutional upper limit of normal
• Patients with abnormal liver function tests (AST/ALT ≤ 3 x institutional upper limits of normal; ALP ≤ 5x ULN; total bilirubin ≤ 2x ULN) will be eligible for enrollment.
• Patients must have adequate renal functions (serum creatinine within normal laboratory limits).
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• Patients who have rapidly progressive intracranial or spinal metastatic disease (including patients who require corticosteroid for CNS disease).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or ketoconazole used in study.
• Patients who have prior medications known to be metabolized by or induce/inhibit CYP3A4 within 1 week of each treatment cycle.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because docetaxel is embryotoxic/fetotoxic with the potential for abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with docetaxel, breastfeeding should be discontinued if the mother is treated with docetaxel. These potential risks may also apply to other agents used in this study.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

Related Publications (2)

• Goh BC, Lee SC, Wang LZ, Fan L, Guo JY, Lamba J, Schuetz E, Lim R, Lim HL, Ong AB, Lee HS. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol. 2002 Sep 1;20(17):3683-90. doi: 10.1200/JCO.2002.01.025.

  PMID: 12202670 BACKGROUND

• Tham LS, Goh BC, Wang LZ, Yong WP, Wong CI, Lee SC, Soo R, Sukri N, Lee HS. Ketoconazole inhibition of CYP3A activity made midazolam but not docetaxel pharmacokinetics more predictable. (Abstr) 2006 American Society for Clinical Pharmacology and Therapeutics Annual Meeting (Baltimore, MD).

  BACKGROUND

MeSH Terms

Interventions

Docetaxel; Ketoconazole

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Boon Cher Goh, MBBS, MRCP

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Goh Boon Cher

Study Record Dates

• First Submitted: June 11, 2008
• First Posted: June 13, 2008
• Study Start: October 1, 2006
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

SG (1)