A Pilot Trial of Calcitriol in Localized Prostate Cancer: Investigation of Biologic Effects and Potential Intermediate Endpoints
- Determine the effect of calcitriol and dexamethasone before radical prostatectomy on
tumor vessel density in patients with localized adenocarcinoma of the prostate.
- Determine the effect of this regimen on the extent of prostatic intraepithelial
neoplasia in these patients.
- Determine the effect of this regimen on the expression of apoptosis markers, p21, p27,
prostate-specific antigen (PSA), prostate-specific membrane antigen, and VDR expression
in tumor-associated vascular endothelial cells and endothelium derived from
normal-appearing prostate and tumor in these patients.
- Determine the acute effects of this regimen on serum PSA in these patients.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a two-stage, randomized, pilot study.
- Stage 1: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral dexamethasone once daily on days 1-4 and oral
calcitriol once daily on days 2-4 weekly for 4 weeks before surgery. Within 48
hours of the last dose, patients undergo radical prostatectomy.
- Arm II: Patients receive no study drugs, but undergo radical prostatectomy.
- Stage 2: If sufficient activity is seen with the dexamethasone and calcitriol regimen
in stage 1, the study is expanded and additional patients are randomized to 1 of 4
- Arm I: Patients receive dexamethasone and calcitriol as in stage 1, arm I.
- Arm II: Patients receive oral dexamethasone once daily on days 1-4.
- Arm III: Patients receive oral calcitriol once daily on days 2-4.
- Arm IV: Patients undergo radical prostatectomy as in stage 1, arm II. In arms I,
II, and III, patients undergo radical prostatectomy as in stage 1, arm I.
Patients are followed at 1, 3, and 12 months.
PROJECTED ACCRUAL: A total of 20-80 patients (20 for stage 1 [10 per treatment arm] and 60
for stage 2) will be accrued for this study within 2 years.
Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Effect of preoperative high-dose calcitriol and dexamethasone on prostatic tumor vessel density measured at 1, 2, 3, and 12 months post prostatectomy
Donald L. Trump, MD
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|