Cholecalciferol and Genistein Before Surgery in Treating Patients With Early Stage Prostate Cancer

Study Overview
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Brief Summary
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This randomized phase II trial studies cholecalciferol and genistein compared to placebo in treating patients with early stage prostate cancer. Cholecalciferol and genistein may slow the growth of cancer cells and may be an effective treatment for prostate cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine differences in prostate tissue steady state concentrations of calcitriol in participants treated with a single dose cholecalciferol (200,000 IU) and G-2535 (which provides 600 mg of genistein) and those receiving placebo. SECONDARY OBJECTIVES: I. To determine the effect of each intervention arm and resulting prostate tissue levels of calcitriol on down-stream related biomarkers and related mechanistic pathways in blood and tissue. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cholecalciferol orally (PO) on day 1 and genistein PO once daily (QD) on days 1-21 or 1-28. Patients then undergo prostatectomy. ARM II: Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy.

Official Title
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Phase IIA, Randomized Placebo-Controlled Trial of Single High Dose Cholecalciferol and Daily Genistein (G-2535) Versus Placebo in Men With Early Stage Prostate Cancer Undergoing Prostatectomy

Conditions
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Prostate Adenocarcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer

Intervention / Treatment
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* Drug: Cholecalciferol
* Drug: Genistein
* Other: Laboratory Biomarker Analysis
* Other: Pharmacological Study
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have microscopic confirmation of adenocarcinoma of the prostate within three months of randomization; clinical stage T1 and T2 a, b, or c are allowed Participants' prostate cancer must be confined to the prostate (in the clinical judgment of the treating physician) Participants must be candidates for prostatectomy Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =<1 (Karnofsky >= 70%) White blood cell (WBC) within normal limits Platelets >= 100 K/uL Hemoglobin >= 10 g/dL Thyroid-stimulating hormone (TSH) =< 4.20 uIU/mL Free T4 =< 12.5 ng/dL Bilirubin within upper limit of normal Aspartate aminotransferase (AST) =< 1.5 x upper limit of normal Creatinine =< 2.0 mg/dL Serum calcium: within institutional normal limits Participants must agree to stop taking nonsteroidal anti-inflammatory drugs (NSAIDS) during the course of the study, however, low dose aspirin (< 100 mg/day) will be allowed; no wash out period is required Participants must be willing to discontinue consuming soy products and ingesting vitamin supplements while participating in this study The effects of cholecalciferol and genistein on the developing human fetus at the recommended therapeutic doses are unknown; for this reason, participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation Participants must have the ability to understand and sign a consent form indicating the investigational nature of the treatment and its potential risks Exclusion Criteria: Participants may not have received any prior therapy for prostate cancer including: chemotherapy, hormonal therapy, brachytherapy, or external radiation Participants may not be receiving concurrent systemic therapy for other cancers Participants may not be receiving any other investigational agents Participants may not be taking the following p450 inducers and inhibitors: carbamazepine, clarithromycin, fluconazole, fosphenytoin, itraconazole, ketoconazole, phenobarbital, phenytoin, rifabutin, rifampin Participants who took finasteride or dutasteride within 6 months of the pre-randomization biopsy, are currently taking finasteride or dutasteride, or are planning on taking these agents during study participation Participants with a history of allergic reactions attributed to genistein or placebo, or compounds of similar chemical or biologic composition Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Participants requires thyroid replacement therapy; Note: participants with a history of thyroid disease > 5 years ago, with current normal thyroid function, will be considered eligible Participant has current, known nephrolithiasis or a history of nephrolithiasis within the past 5 years Participant has any history of sarcoidosis

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (cholecalciferol, genistein)<br>Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. | Drug: Cholecalciferol<br>* Given PO<br>* Other names: Vitamin D3;Drug: Genistein<br>* Given PO<br>* Other names: Prunetol;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>Other: Placebo<br>* Given PO<br>* Other names: sham therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue Levels of Calcitriol Between the Placebo and Cholecalciferol/Genistein Arms | This is a measure of calcitriol in prostate tissue comparing placebo and cholecalciferol/genistein | up to Day 35 | 
| Detectability of Calcitriol Levels in Tissue Between the Placebo and Cholecalciferol/Genistein Arms | To identify the amount of Calcitriol that is found in the tissue comparing Placebo and Cholecalciferol/Genistein | up to 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of Calcidiol in the Participants Serum | This is measuring the amount of Calcidiol that was found in the participants blood Serum at baseline and end of study | Baseline and up to day 35 | 
| Levels of Calcitriol in Participants Serum | This is measuring the amount of Calcitriol that was found in the participants blood Serum at baseline and end of study. | baseline and Up to Day 35 | 
| PBMC CYP mRNA Expression of CYP24 | This is a measure of expression of CYP24 in comparing placebo to Cholecalciferol/genistein. | Baseline and Up to Day 35 | 
| PBMC CYP mRNA Expression of CYP27B1 | This is a measure of expression of CYP27B1 in comparing placebo to Cholecalciferol/genistein. | Up to Day 35 | 
| Total PSA in Serum | This is a measure of the concentration of PSA in the blood serum at baseline and at the end of study. | at Baseline and up to Day 35 | 
| Serum Calcium Levels at Baseline and Pre-Surgery | This is a measurement of calcium in the Blood serum at baseline and at the end of the study. | Baseline and Day 35 | 
| Total IGF-1 in Serum at Baseline and Pre-Surgery | This is measuring the concentration of the Biomarker IGF-1 in blood serum at Baseline and at the end of the study. | Baseline and up to Day 35 | 
| Total IGF-2 in Serum at Baseline and Pre-Surgery | This is measuring the concentration of the Biomarker IGF-2 in blood serum at Baseline and at the end of the study | Baseline and Up to Day 35 | 
| Total IGFBP-3 in Serum at Baseline and Pre-Surgery | This is measuring the concentration of the Biomarker IGFBP-3 in blood serum at Baseline and at the end of the study. | Baseline and Up to Day 35 | 
| Total PTH in Serum at Baseline and Pre-Surgery | This is measuring the concentration of the Biomarker PTH in blood serum at Baseline and at the end of the study | Baseline and Up to Day 35 | 
| Immunohistochemistry Measurements in Benign Prostate Tissue (BPT) | The Immunohistochemistry measurement for: AR (Nucleus), VDR (Cytoplasm), p21 (Nucleus), PGE2 (Cytoplasm), TUNEL Pos (Nucleus), Caspase 3 (Cytoplasm), PSMA (Cytoplasm), IGF-1 and IGF-2 (Cytoplasm), Akt (Nucleus and Cytoplasm), and pAkt (nucleus and Cytoplasm) This is to serve as normalized control data to determine expression of protein. The normalized optical densities were measured as optical density per unit area by densitometric scanning using Vectra imaging system (Perkin Elmer). This Optical Density is based on fluorescence. | Up to Day 35 | 
| Immunohistochemistry Measurements in Prostate Cancer Tissue (PCA) | The Immunohistochemistry measurement for: AR (Nucleus), VDR (Cytoplasm), p21 (Nucleus), PGE2 (Cytoplasm), TUNEL Pos (Nucleus), Caspase 3 (Cytoplasm), PSMA (Cytoplasm), IGF-1 and IGF-2 (Cytoplasm), Akt (Nucleus and Cytoplasm), and pAkt (nucleus and Cytoplasm) This is to serve as normalized case data to determine expression of protein. The normalized optical densities were measured as optical density per unit area by densitometric scanning using Vectra imaging system (Perkin Elmer). This Optical Density is based on fluorescence. | Up to day Day 35 | 
| Percent of Participants With CYP24 and CYP27B1 SNPs (DNA From Paxgene) |  | up to Day 35 |