Vitamin D Effects on Prostate Pathology (DProstate)

Randomized Trial of the Effects of Vitamin D on Prostate Cancer-associated Lesions and on Vitamin D Metabolites in Prostate

There is much interest in understanding the role that vitamin D3 (cholecalciferol) plays in various cancers, and in the prognosis of various cancers once they are discovered. The purpose of this study is to examine the effects of vitamin D on prostate cancer-associated lesions and on vitamin D metabolites in prostate tissue. We will give vitamin D3 to men when they are scheduled to have their prostate removed because of cancer. The men will take vitamin D at one of 3 doses for 4-6 weeks, until the surgery is performed. We will compare the prostate tissue taken from the men receiving the higher doses of vitamin D to tissue from men assigned to the lower doses. We expect to find that the prostate removed at surgery from men who received the high-dose vitamin D treatment will appear more normal, and less cancer like. In addition, we will measure vitamin D metabolites in the prostate to confirm that these did accumulate in the prostate to bring about the effects observed.

Study Overview

• Status: Unknown
• Conditions: Prostate Cancer
• Intervention / Treatment: Dietary supplement: vitamin D3 (cholecalciferol)

Detailed Description

Epidemiologic, laboratory, and clinical reports all suggest that vitamin D3 (cholecalciferol) plays a desirable role in the prevention and prognosis of prostate and other cancers. Prostate cancer cells possess both of the enzymes required to convert vitamin D to the active paracrine hormone, calcitriol. However, the dose-response relationship between serum levels of calcidiol (vitamin D status) and prostate tissue levels of calcidiol and calcitriol is yet to be defined. As a neoadjuvant, prior to radical prostatectomy (for 4-6 wk) vitamin D3 [400 IU (control group), 10,000 IU or 40,000 IU/day] will be given to 90 men randomized, double-blinded, 30 per dose. Immediately after surgery, the pathologist will obtain a few grams of prostate tissue, some of which will be used to assay calcidiol and calcitriol within prostate. From the embedded prostate, we will prepare immunohistochemically stained sections to characterize cellular responses and morphological changes. Our hypothesis is that vitamin D will increase intraprostate calcitriol concentration and thereby lower cellular proliferation (as judged by the markers MIB-1 and p27) in zones of Gleason pattern 3 prostate cancer and in pre-cancerous (PIN) lesions. We expect that our results will provide surrogate outcomes to justify larger trials of vitamin D for treatment of prostate cancer. This research has the potential to: 1. Provide direct evidence at the cellular level using clinical samples that vitamin D lowers cellular proliferation in prostate cancer, 2. Provide guidance about the serum calcidiol concentrations (and thereby vitamin D doses) that should be targeted for such studies, and 3. Eventually support other research directed at vitamin D as a primary prevention strategy.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Diagnosis of a Gleason score 6 or 7 adenocarcinoma of the prostate biopsy
• Patient has elected to have a radical prostatectomy
• Patient is determined fit for surgery
• Normal renal and hepatic function
• Normal serum and urine calcium values
• Normal serum phosphate values
• Normal serum parathyroid hormone values
• Signed written informed consent

Exclusion Criteria:

• Prior use of neoadjuvant androgen deprivation therapy
• Prior use of 5 alpha reductase inhibitors (finasteride or dutasteride) in last 12 months
• Previous or concomitant anti-cancer therapy (chemotherapy, radiotherapy)
• Gleason score 8-10 adenocarcinoma as a biopsy diagnosis
• History of hypercalcemia/hypercalciuria
• History of renal disease
• History of sarcoidosis
• Vitamin D (cholecalciferol) supplement > 1000 IU/day
• Inability to comply with a study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; vitamin D3 (400 IU/d)	Dietary supplement: vitamin D3 (cholecalciferol); liquid vitamin D solution (vitamin D3 in ethanol) taken daily at one of three possible doses (400, 10000, or 40000 IU/d) for 4-6 weeks prior to radical prostatectomy
Active Comparator: 2; vitamin D3 (10,000 IU/d)	Dietary supplement: vitamin D3 (cholecalciferol); liquid vitamin D solution (vitamin D3 in ethanol) taken daily at one of three possible doses (400, 10000, or 40000 IU/d) for 4-6 weeks prior to radical prostatectomy
Active Comparator: 3; vitamin D3 (40,000 IU/d)	Dietary supplement: vitamin D3 (cholecalciferol); liquid vitamin D solution (vitamin D3 in ethanol) taken daily at one of three possible doses (400, 10000, or 40000 IU/d) for 4-6 weeks prior to radical prostatectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
immunohistochemical markers of prostate pathology	end-of-study
intraprostate vitamin D metabolites	end-of-study

Secondary Outcome Measures

Outcome Measure	Time Frame
calcium (serum and urine)	biweekly
parathyroid hormone (PTH)	baseline, final
prostate specific antigen (PSA)	baseline, final
creatinine (serum and urine)	biweekly
phosphate (serum)	biweekly
serum vitamin D metabolites	baseline, final

Collaborators and Investigators

• Sponsor: University of Toronto
• Collaborators: University Health Network, Toronto; Sunnybrook Health Sciences Centre; Mount Sinai Hospital, Canada; Canadian Cancer Society (CCS)
• Investigators: Principal Investigator: Neil Fleshner, MD, MPH, FRCSC, University Health Network, Toronto; Principal Investigator: Reinhold Vieth, PhD, University of Toronto, Mount Sinai Hospital; Study Director: Dennis Wagner, MSc, University of Toronto, Mount Sinai Hospital; Principal Investigator: Theo van der Kwast, MD, PhD, FRCPC, University Health Network, Toronto; Principal Investigator: Laurence Klotz, MD, FRCSC, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Anticipated): February 1, 2012
• Study Completion (Anticipated): July 1, 2012

Study Registration Dates

• First Submitted: August 25, 2008
• First Submitted That Met QC Criteria: August 25, 2008
• First Posted (Estimate): August 26, 2008

Study Record Updates

• Last Update Posted (Estimate): September 30, 2011
• Last Update Submitted That Met QC Criteria: September 29, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: prostate cancer; vitamin D; prostatectomy; immunohistochemistry; pathology
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: M2140