Calcitriol, Ketoconazole, and Hydrocortisone in Treating Patients With Advanced or Recurrent Prostate Cancer
RATIONALE: Calcitriol may help prostate cancer cells become more like normal cells and grow and spread more slowly. Ketoconazole may help calcitriol work better by making tumor cells more sensitive to the drug. Giving calcitriol together with ketoconazole and hydrocortisone may be an effective treatment for prostate cancer.
PURPOSE: This phase I/II trial is studying the side effects and best dose of calcitriol when given together with ketoconazole and hydrocortisone and to see how well it works in treating patients with advanced or recurrent prostate cancer.
Dietary Supplement: calcitriol
Drug: therapeutic hydrocortisone
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Oral Calcitriol in Combination With Ketoconazole in Androgen Independent Prostate Cancer|
- Maximum tolerated dose of calcitriol (phase I) [ Time Frame: In 4 week cycles ] [ Designated as safety issue: Yes ]
- Prostate-specific antigen response rate (complete and partial) (phase II) [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
- Toxicity as measured by NCI CTC version 3.0 [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
- Objective tumor response as measured by monthly physical exam and radiographic evaluation every 12 weeks [ Time Frame: Monthly and at 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||October 2006|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dose-escalation of calcitriol)
PHASE I: Patients receive calcitriol PO QD on days 1-3, 8-10, 15-17, and 22-24. Patients also receive ketoconazole PO TID on days 1-24 and therapeutic hydrocortisone PO BID on days -1 to 24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients receive calcitriol and therapeutic hydrocortisone as in phase I. Patients also receive ketoconazole PO TID on days 4-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dietary Supplement: calcitriol
Given OrallyDrug: therapeutic hydrocortisone
- To determine the maximum tolerated dose (MTD) of oral calcitriol when given together with ketoconazole and hydrocortisone in patients with advanced or recurrent androgen-independent prostate cancer. (Phase I)
- To estimate the prostate-specific antigen response rate. (Phase II)
- To evaluate the pharmacokinetics of the phase II dose of calcitriol with and without ketoconazole.
- Describe any objective tumor responses to the combination of calcitriol, ketoconazole, and hydrocortisone among patients with measurable disease using RECIST criteria.
- Explore the pharmacodynamic effects of this combination in peripheral blood mononuclear cells.
- Determine toxicities and tolerability of this regimen.
OUTLINE: This is a phase I, dose-escalation study of calcitriol followed by a phase II study.
- Phase I: Patients receive oral calcitriol once daily on days 1-3, 8-10, 15-17, and 22-24, oral ketoconazole three times daily on days 1-28, and oral hydrocortisone twice daily on days 0-28 of course 1 and days 1-28 of all subsequent courses. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of calcitriol 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.
- Phase II: Patients receive oral calcitriol at the MTD determined in phase I on days 1-3, 8-10, 15-17, and 22-24, oral ketoconazole three times daily on days 4-28, and oral hydrocortisone as in phase I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Peripheral blood mononuclear cells are collected periodically to evaluate the pharmacodynamics of calcitriol, hydrocortisone, and ketoconazole. Some patients undergo blood collection on days 1 and 15 for calcitriol pharmacokinetic studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00536991
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263-0001|
|Contact: AskRPCI 877-275-7724 AskRPCI@RoswellPark.org|
|Principal Investigator:||Donald L. Trump, MD||Roswell Park Cancer Institute|