Clinical trial NCT00741364: Vitamin D Effects on Prostate Pathology
Official title: Randomized Trial of the Effects of Vitamin D on Prostate Cancer-associated Lesions and on Vitamin D Metabolites in Prostate
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: vitamin D
prostate cancer
prostatectomy
pathology
immunohistochemistry
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: Mount Sinai Hospital, Canada
name: University Health Network, Toronto
name: Sunnybrook Health Sciences Centre
name: Canadian Cancer Society (CCS)
First posted: 2008-08-26
Enrollment: 90
Sex: MALE
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: immunohistochemical markers of prostate pathology
timeFrame: end-of-study
measure: intraprostate vitamin D metabolites
timeFrame: end-of-study
Secondary outcomes:
measure: calcium (serum and urine)
timeFrame: biweekly
measure: parathyroid hormone (PTH)
timeFrame: baseline, final
measure: prostate specific antigen (PSA)
timeFrame: baseline, final
measure: creatinine (serum and urine)
timeFrame: biweekly
measure: phosphate (serum)
timeFrame: biweekly
measure: serum vitamin D metabolites
timeFrame: baseline, final
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University of Toronto, Mount Sinai Hospital
name: Reinhold Vieth, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto, Mount Sinai Hospital
name: Dennis Wagner, MSc
role: STUDY_DIRECTOR
affiliation: University Health Network, Toronto
name: Theo van der Kwast, MD, PhD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Neil Fleshner, MD, MPH, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Laurence Klotz, MD, FRCSC
role: PRINCIPAL_INVESTIGATOR
References: