Calcitriol and Dexamethasone Before Radical Prostatectomy in Treating Patients With Localized Adenocarcinoma (Cancer) of the Prostate

Study Overview
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Brief Summary
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RATIONALE: Calcitriol and dexamethasone may slow the growth of prostate cancer cells. PURPOSE: This randomized phase II trial is studying how well giving calcitriol together with dexamethasone before radical prostatectomy works in treating patients with localized stage II or stage III adenocarcinoma (cancer) of the prostate.

Detailed Description
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OBJECTIVES: 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 treatment arms. 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.

Official Title
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A Pilot Trial of Calcitriol in Localized Prostate Cancer: Investigation of Biologic Effects and Potential Intermediate Endpoints

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: calcitriol
* Drug: dexamethasone
* Other: clinical observation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Organ-confined disease cT1, cT2, or cT3 tumors Patients with cT1 tumors are eligible if ≥ 1 core biopsies have ≥ 50% of the tumor OR if 50% of the cores examined contain the tumor No small cell carcinoma of the prostate Scheduled for radical prostatectomy PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic Platelet count ≥ 100,000/mm^3 WBC ≥ 3,500/mm^3 Hepatic ALT and AST ≤ 4 times normal Bilirubin ≤ 2 mg/dL Renal Creatinine ≤ 2 times upper limit of normal Calcium ≤ 10.5 mg/dL No detectable renal stones by CT scan or ultrasound Other No history of diabetes mellitus requiring pharmacotherapy PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy More than 5 years since prior antiestrogens, antiandrogens, luteinizing hormone-releasing hormone agonists, estrogen, or progestational agents Radiotherapy Not specified Surgery See Disease Characteristics No prior nephrectomy No prior prostatic surgery No prior cryotherapy or transurethral resection of the prostate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1, Arm I<br>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. | Dietary Supplement: calcitriol<br>* Given orally<br>Drug: dexamethasone<br>* Given orally<br>|
| Experimental: Stage 1, Arm II<br>No study drugs before surgery. | Other: clinical observation<br>* No intervention before surgery<br>|
| Experimental: Stage 1 Arm 3<br>Patients receive oral dexamethasone once daily on days 1-4. | Drug: dexamethasone<br>* Given orally<br>|
| Experimental: Stage 1, Arm 4<br>Patients receive oral calcitriol once daily on days 2-4. | Dietary Supplement: calcitriol<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Preoperative High-dose Calcitriol and Dexamethasone on Prostatic Tumor Vessel Density Measured at 1, 2, 3, and 12 Months Post Prostatectomy |  | Up to 30 days of the last administration of study procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Preoperative High-dose Calcitriol and Dexamethasone on Extent of Prostatic Intraepithelial Neoplasia (PIN) at 1, 2, 3, and 12 Months Post Prostatectomy |  | Up to 30 days of the last administration of study procedure | 
| Determine the Effect of This Regimen on the Expression of Apoptosis Markers | 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. | Up to 30 days of the last administration of study procedure | 
| Determine the Acute Effects of This Regimen on Serum PSA in These Patients. |  | Up to 30 days of the last administration of study procedure | 
| Number of Participants With Adverse Events, Graded According to NCI CTCAE v2.0 | Number of Participants with Adverse Events, Graded According to NCI CTCAE v2.0 | Up to 30 days of the last administration of study procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage II prostate cancer, stage III prostate cancer