Cholecalciferol Supplement in Treating Patients With Localized Prostate Cancer Undergoing Observation

Study Overview
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Brief Summary
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This randomized clinical trial studies how well cholecalciferol supplement works in treating patients with localized prostate cancer undergoing observation. Cholecalciferol may help prostate cancer cells become more like normal cells, and to grow and spread more slowly.

Detailed Description
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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.

Official Title
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Randomized Placebo-Controlled, Double-Blind Study of Cholecalciferol Replacement in Patients on Expectant Management for Localized Prostate Cancer

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Dietary Supplement: Cholecalciferol
* Other: Laboratory Biomarker Analysis
* Other: Patient Observation
* Drug: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (cholecalciferol and placebo)<br>Patients receive cholecalciferol 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 II. | Dietary Supplement: Cholecalciferol<br>* Given PO<br>* Other names: Vitamin D3;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Patient Observation<br> <br> * Other names: Watchful Waiting;Drug: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (placebo and cholecalciferol)<br>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. | Dietary Supplement: Cholecalciferol<br>* Given PO<br>* Other names: Vitamin D3;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Patient Observation<br> <br> * Other names: Watchful Waiting;Drug: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA Response | Difference in the mean change in PSA on vitamin D (9 month period: pre-Vitamin D to 9 months after start of vitamin D) versus on placebo (9 month period: pre-Placebo to 9 months after starting placebo). Compared using a paired t-test. | 9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of PSA Concentration Over Time | The PSA levels were modeled as a function of treatment, time, their interaction, sequence, and a random subject effect using a linear mixed model. From this model, the subject specific PSA slope was obtained for each subject under each condition (vitamin D versus placebo). The PSA slopes were then compared between treatment conditions using linear mixed model to account for treatment arm and repeated measures. | 9 month period: pre-Vitamin D/pre-placebo to 9 months after start of vitamin D/ placebo, up to 30 days after completion of study treatment -Up to 30 days after completion of study treatment | 
| Toxicity as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Summarizing the maximum observed treatment related adverse event. Summarize by arm and grade using frequencies and relative frequencies.. | Up to 30 days after completion of study treatment (up to 22 months from start of study). |