Calcitriol in Preventing Prostate Cancer in Patients With Prostatic Intraepithelial Neoplasia

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of calcitriol may prevent prostate cancer. It is not yet known whether calcitriol is more effective than observation in preventing prostate cancer. PURPOSE: This randomized phase II trial is studying how well calcitriol works in preventing prostate cancer in patients with prostatic intraepithelial neoplasia.

Detailed Description
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OBJECTIVES: Determine the effects of calcitriol in patients with high-grade prostatic intraepithelial neoplasia. Determine the toxicity of this drug in these patients. Determine the effect of this drug on prostate specific antigen in these patients. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 arms. Arm I: Patients receive oral calcitriol once daily for 8 weeks. Treatment repeats every 8 weeks for 2 courses in the absence of unacceptable toxicity. After completion of course 2 (week 16), patients undergo biopsy. Patients continue to receive calcitriol for up to 3 additional weeks while the biopsy is being evaluated. Patients with persistent high-grade prostatic intraepithelial neoplasia (HGPIN) by biopsy receive 2 additional courses of calcitriol. Patients with no HGPIN or prostate cancer by biopsy are removed from the study. Arm II: Patients undergo observation for 16 weeks. At week 16, patients undergo biopsy. Patients with persistent HGPIN by biopsy receive 2 courses of calcitriol as in arm I. Patients with no HGPIN or prostate cancer by biopsy are removed from the study. After completion of study treatment, patients are followed annually for 2 years. PROJECTED ACCRUAL: A total of 50 patients (25 per arm) will be accrued for this study.

Official Title
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A Randomized Phase II Trial Of Calcitriol In Patients With Prostatic Intraepithelial Neoplasia

Conditions
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Precancerous/Nonmalignant Condition, Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: calcitriol
* Procedure: observation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed high-grade prostatic intraepithelial neoplasia Diagnosed within the past 6 months No evidence of prostate cancer within the past 6 months No evidence of palpable nodules on digital rectal exam Prostate specific antigen ≤ 10 ng/mL within the past 3 months PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic SGOT and SGPT ≤ 1.5 times upper limit of normal Renal No uncontrolled renal failure No cancer-related hypercalcemia or kidney stones within the past 5 years Cardiovascular No uncontrolled coronary artery disease No uncontrolled congestive heart failure Other Prior malignancy allowed provided patient was curatively treated and has been disease-free for an appropriate time period for the specific cancer No known HIV positivity No active infection No major depression or suicidal ideation No other condition that would preclude study compliance No other uncontrolled medical condition PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for any malignancy Endocrine therapy At least 2 weeks since prior and no concurrent finasteride (Prosear® or Propecia®) or other androgen suppressor No concurrent corticosteroids Radiotherapy Not specified Surgery Not specified Other At least 2 weeks since prior phenytoin or phenobarbital At least 2 weeks since prior ketoconazole No concurrent administration of any of the following: Magnesium-containing antacids Thiazide diuretics Calcium supplements Digoxin Herbal supplements Pharmacological doses of cholecalciferol (vitamin D) or its derivatives

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral calcitriol once daily for 8 weeks. Treatment repeats every 8 weeks for 2 courses. After completion of course 2 (week 16), patients undergo biopsy. Patients continue to receive calcitriol for up to 3 additional weeks while the biopsy is being evaluated. Patients with persistent high-grade prostatic intraepithelial neoplasia (HGPIN) by biopsy receive 2 additional courses of calcitriol. | Dietary Supplement: calcitriol<br>* Given orally<br>|
| Other: Arm II<br>Patients undergo observation for 16 weeks. At week 16, patients undergo biopsy. Patients with persistent HGPIN by biopsy receive 2 courses of calcitriol as in arm I. | Dietary Supplement: calcitriol<br>* Given orally<br>Procedure: observation<br>* No initial intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of prostate intraepithelial neoplasia after 16 weeks |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, high grade prostatic intraepithelial neoplasia