Ketoconazole and Docetaxel in Treating Patients With Metastatic Prostate Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Prostate Cancer
Intervention: docetaxel (Drug); ketoconazole (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: National Cancer Institute (NCI) Official(s) and/or principal investigator(s):
William Dahut, MD, Principal Investigator, Affiliation: National Cancer Institute (NCI)
Summary
RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as
ketoconazole may stop the adrenal glands from producing androgens. Drugs used in chemotherapy
use different ways to stop tumor cells from dividing so they stop growing or die. Combining
ketoconazole with docetaxel may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining ketoconazole with docetaxel in
treating patients who have metastatic prostate cancer.
Clinical Details
Official title: A Phase I Trial Of High Dose Ketoconazole Plus Weekly Docetaxel In Metastatic Androgen Independent Prostate Cancer
Study design: Treatment
Detailed description:
OBJECTIVES:
- Determine the maximum tolerated dose and recommended phase II dose of ketoconazole when
administered in combination with docetaxel in patients with metastatic
androgen-independent prostate cancer.
- Determine the side effect profile of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine any clinical activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of docetaxel.
Patients receive docetaxel IV over 1 hour once weekly on days 1, 8, and 18 and oral
ketoconazole three times daily on days 15-28 for the first course. For the second and
subsequent courses, patients receive docetaxel IV on days 1, 8, and 15 and oral ketoconazole
daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable
toxicity.
Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Patients are followed every 4 weeks.
PROJECTED ACCRUAL: Approximately 3-55 patients will be accrued for this study within 2
years.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Male.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed prostate cancer
- Metastatic androgen-independent disease
- Progression during hormonal ablation (e. g., luteinizing-hormone releasing-hormone
[LHRH] agonist therapy) defined as at least 1 of the following:
- Two consecutive rising PSA levels at least 1 week apart with at least 1 that is
at least 50% above the nadir reached after the last therapy (must be at least 5
ng/mL)
- At least 1 new metastatic deposit on technetium Tc 99m dextran bone scintigraphy
- Progression of soft tissue metastases by imaging or palpation (development of new
area of malignant disease or measurable disease progression)
- If no prior surgical castration, all of the following criteria must be met:
- Concurrent LHRH agonist therapy
- Concurrent gonadotropin-releasing hormone-agonist therapy
- Testosterone less than 50 ng/mL
- No brain metastases
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- More than 3 months
Hematopoietic:
- Granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin less than 1. 0 mg/dL
- AST and ALT less than 2. 5 times upper limit of normal (ULN)
- Alkaline phosphatase less than 2. 5 times ULN
Renal:
- Creatinine no greater than 1. 5 mg/dL OR
- Creatinine clearance at least 40 mL/min
Cardiovascular:
- No unstable or newly diagnosed angina pectoris
- No myocardial infarction within the past 6 months
- No New York Heart Association class II-IV heart disease
Other:
- Able to ingest oral medications
- No other active malignancy within the past 2 years except nonmelanoma skin cancer or
carcinoma in situ of the bladder
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Not specified
Endocrine therapy:
- See Disease Characteristics
- At least 4 weeks since prior flutamide
- At least 6 weeks since prior bicalutamide or nilutamide
Radiotherapy:
- No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
Surgery:
- Recovered from prior surgery
Other:
- Recovered from prior therapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent theophylline
- No concurrent cisapride
- No concurrent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors (e. g.,
lovastatin, atorvastatin, simvastatin, pravastatin, or cerivastatin)
- No concurrent known inhibitors and/or inducers of CYP3A4
- No concurrent terfenadine, midazolam, triazolam, alprazolam, astemizole, loratadine,
rifampin, isoniazid, dofetilide, pimozide, sirolimus, or erythromycin
- No concurrent drugs that decrease gastric acid output or increase gastric pH (e. g.,
antacids, cimetidine, ranitidine, antimuscarinics, omeprazole, or lansoprazole)
- No concurrent warfarin
Locations and Contacts
NCI - Center for Cancer Research, Bethesda, Maryland 20892-8200, United States; Recruiting
David Draper, Phone: 301-435-5614
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office, Bethesda, Maryland 20892-1182, United States; Recruiting
Clinical Trials Office - Warren Grant Magnusen Clinical Center, Phone: 888-NCI-1937
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database Web site for additional information
Starting date: April 2002
Last updated: January 9, 2009
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