Official Title: “A Phase I Trial Of High Dose Ketoconazole Plus Weekly Docetaxel In Metastatic Androgen Independent Prostate Cancer”

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.

Study Type: Interventional

Study Design: Treatment

Study Primary Completion Date: March 2008

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.

Intervention(s) in this Clinical Trial

• Drug: docetaxel
• Drug: ketoconazole

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

William Dahut, MD Study Chair National Cancer Institute (NCI)  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00039221

Study ID Number: CDR0000069364

ClinicalTrials.gov Identifier: NCT00039221

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database

Web site for additional information