Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Ketoconazole and Docetaxel in Treating Patients With Metastatic Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active 18 and over NCI NCI-02-C-0149 NCT00039221

Special Category: NIH Clinical Center trial

Objectives

1. 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.
2. Determine the side effect profile of this regimen in these patients.
3. Determine the pharmacokinetics of this regimen in these patients.
4. Determine any clinical activity of this regimen in these patients.

Entry 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

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• Granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

Approximately 3-55 patients will be accrued for this study within 2 years.

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.

Figg WD, Liu Y, Acharya MR, et al.: A phase I trial of high dose ketoconazole plus weekly docetaxel in metastatic androgen independent prostate cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1731, 2003.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

William Dahut, MD, Principal investigator		Ph: 301-435-8183 Email: dahutw@mail.nih.gov

U.S.A.
Maryland
	Bethesda
	NCI - Center for Cancer Research
		David Draper	Ph:  301-435-5614
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Web site for additional information

Registry Information
Official Title		A Phase I Trial Of High Dose Ketoconazole Plus Weekly Docetaxel In Metastatic Androgen Independent Prostate Cancer
Trial Start Date		2002-04-02
Trial Completion Date		2008-03-31 (estimated)
Registered in ClinicalTrials.gov		NCT00039221
Date Submitted to PDQ		2002-04-08
Information Last Verified		2009-01-07

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