A Phase I/II Study of Oral Calcitriol in Combination With Ketoconazole in Androgen Independent Prostate Cancer
- 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
- 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
- Determine toxicities and tolerability of this regimen.
OUTLINE: This is a phase I, dose-escalation study of calcitriol followed by a phase II
- 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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of calcitriol (phase I)
In 4 week cycles
Donald L. Trump, MD
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|