Ketoconazole Plus Docetaxel to Treat Prostate Cancer

Prostatic Neoplasms Clinical Trial

Official title: A Phase I Trial of High Dose Ketoconazole Plus Weekly Docetaxel in Metastatic Androgen Independent Prostate Cancer

Status Completed

Clinical Trial Summary

This study will determine the maximum dose of docetaxel that can be given safely in combination with ketoconazole for treating advanced prostate cancer. Docetaxel is approved for the treatment of several other types of cancers; ketoconazole is an approved antifungal medication that is also commonly used in high doses to treat prostate cancer.

Patients 18 years of age and older with advanced prostate cancer that does not respond to hormone therapy may be eligible for this study. Candidates will be screened with blood tests to evaluate liver, kidney and other organ function and with x-rays, scans, or other imaging tests to determine the extent of disease.

Participants will take the following medications:

• Docetaxel daily, infused through a vein over 30 minutes, in 4-week cycles-3 consecutive weeks of drug followed by one week of rest

• Dexamethasone, 12 hours and 1 hour before and 12 hours after docetaxel infusions to help prevent fluid retention caused by the docetaxel

• Ketoconazole, 3 times a day

• Hydrocortisone, twice a day to replace a loss of natural steroids caused by the ketoconazole

Patients will be hospitalized 1 to 2 days each for the first and second doses of docetaxel to allow for frequent blood draws to measure blood levels of the drug. Ketoconazole will be started about 2 weeks after the first dose of docetaxel and the second dose of docetaxel will be given 2 days after that. In order to determine the maximum tolerated dose of docetaxel, the first few patients in the study will be given a low dose of the drug, and subsequent patients will get increasingly higher doses until unacceptable side effects occur. Because prostate cancer cells may grow if exposed to testosterone, patients may have to have their testosterone production suppressed either surgically (removal of the testicles) or medically with an injection of leuprolide or goserelin, which are luteinizing hormone-release hormone agonists that reduce the amount of testosterone.

Imaging studies, such as x-rays, bone scans or computed tomography (CT) scans, will be done about every 3 months to examine how the tumor is responding to therapy. After six treatment cycles, patients will have monthly chest x-rays to check for fluid around the lining of the lungs, which may occur as a result of docetaxel therapy.

Treatment is expected to continue for at least 3 to 6 months, although this time could be shortened or extended depending on the tumor response to therapy or side effects of the drugs. Patients who do not experience bad side effects and whose tumor does not grow during the first 3 treatment cycles will continue treatment; those who experience unacceptable side effects will be taken off the study.

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Clinical Trial Description

High dose ketoconazole and weekly docetaxel have both been shown to have activity against androgen independent prostate cancer (AIPC). We have demonstrated synergy in prostate cancer in an in vitro model. This is an open label phase I study of high-dose ketoconazole plus weekly docetaxel in patients with metastatic AIPC. The primary objective of this study will be to determine the side effect profile of ketoconazole when combined with weekly docetaxel therapy and determine the maximum tolerated dose (MTD) and a recommended phase II dose (RPIID) of docetaxel when combined with high dose ketoconazole. Since ketoconazole may alter the metabolism of docetaxel, this study will evaluate potential drug interactions and adverse events between these two agents. Ketoconazole dose will be 600mg per day (given 200 mg, three times a day), plus 30mg of hydrocortisone (20mg in the morning and 10mg in the evening), plus docetaxel 10-43 mg/m(2) in a dose escalation, repeated in 28-day cycles, comprising weekly treatments for three consecutive weeks followed by one week off. Each patient will be evaluated every four weeks for the duration of the study. ;

Related Conditions & MeSH terms

• Prostatic Neoplasms

• NCT number: NCT00032825
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: March 19, 2002
• Completion date: June 13, 2011