Cholecalciferol Supplement in Treating Patients With Localized Prostate Cancer Undergoing Observation

PRIMARY OBJECTIVES:

I. To determine the prostate-specific antigen (PSA) response with oral high dose vitamin D3
supplementation (cholecalciferol) in patients with localized, histologically proven
adenocarcinoma of the prostate who have not received any treatment for prostate cancer ever
and have chosen expectant management.

SECONDARY OBJECTIVES:

I. To examine the pattern of response of PSA dynamics as well as the absolute change in PSA
following vitamin D3 supplementation.

II. Assess the toxicity of vitamin D3 supplementation in men with prostate cancer.

TERTIARY OBJECTIVES:

I. Track occurrence of infections, deep venous thrombosis, vascular events and falls in the
study population.

II. To evaluate relationship between cytochrome P450 family 24 (CYP24), 27B1,
single-nucleotide polymorphism (SNPs) and serum 25(hydroxy [OH]) vitamin D response to oral
D3 supplementation.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cholecalciferol orally (PO) once daily (QD) for 9 months in the
absence of disease progression or unacceptable toxicity. After a wash-out period of 3 months,
patients cross-over to Arm II.

ARM II: Patients receive placebo PO QD for 9 months in the absence of disease progression or
unacceptable toxicity. After a wash-out period of 3 months, patients cross-over to Arm I.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Any patient with clinically localized, histologically proven adenocarcinoma of
prostate who has not received any treatment for prostate cancer ever and has chosen
active surveillance; treatment for prostate cancer is defined as prostatectomy,
androgen deprivation, brachytherapy or a full course of external beam irradiation

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Willingness to comply with study guidelines

- Willingness and ability to consent

- 25(OH) D3 level less than 40 ng/ml within 3 months of initiation of study; most recent
25 hydroxy D level within last 3 month would be used

Exclusion Criteria:

- History of malabsorption syndrome e.g., pancreatic insufficiency, celiac disease,
tropical sprue

- Creatinine > 2.0 mg/dL

- Corrected serum calcium level of > 10.5 mg/dL (serum corrected calcium = serum calcium
+ 0.8[4-serum albumin])

- Most recent PSA value more than 18 months ago

- Prior or current therapy for prostate cancer

- Documented history of nephrolithiasis within the past 5 years

- Patients receiving finasteride (Proscar) or dutasteride (Avodart) or men who have
received either agent within 90 days of entry are ineligible

- Patients cannot take any additional vitamin D supplementation during study treatment;
patients taking > 2000 IU per day prior to treatment will be ineligible