Ketoconazole Plus Docetaxel to Treat Prostate Cancer

Completed · Phase 1

Conditions studied: Prostatic Neoplasms

In brief

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. ...

Key facts

Study ID: NCT00032825
Run by: National Cancer Institute (NCI)
People needed: 674
Starts: 2002-03-19
Expected to finish: 2011-06-13
Last updated by the study team: 2019-11-21

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may not qualify if…

Patients with brain metastases will not be eligible.
Patients who have received strontium or samarium will not be eligible.
HIV-positive patients receiving combination anti-retroviral therapy will be excluded because of possible pharmacokinetic interactions with ketoconazole, docetaxel or other agents administered during the study. In fact, ketoconazole has been found to increase the toxic effects of several protease inhibitors by affecting CYP3A4 activity.
Patients on theophylline will be excluded.
Patients who are receiving cisapride will be excluded.
Patients who are receiving HMG-CoA inhibitors (lovastatin, atorvastatin, simvastatin, pravastatin and cerivastatin)
Patients currently taking known inhibitors and/or inducers of CYP3A4; patients taking known substrates of CYP3A4 will be evaluated by the primary investigator.
Patients who are receiving terfenadine, midazolam, triazolam, alprazolam, astemizole, loratadine, rifampin, isoniazid, dofetilide, pimozide, sirolimus or erythromycin will be excluded.
Because gastric acidity is necessary for the dissolution and absorption of ketoconazole, concomitant administration of drugs which decrease gastric acid output or increase gastric pH (e.g., antacids, cimetidine, ranitidine, antimuscarinics, omeprazole, and lansoprazole) may decrease absorption and thus will be prohibited.
Patients requiring warfarin will be excluded.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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