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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01325311
• Collaborator: (none)
• Enrollment: 15
• Locations: 11
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Adenocarcinoma; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer	Drug: Cholecalciferol; Drug: Genistein; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (cholecalciferol, genistein) Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy.	Drug: Cholecalciferol; Given PO; Other Names: 9,10-Secocholesta-5,7,10(19)-trien-3-ol Calciol Delsterol Vitamin D3 ; Drug: Genistein; Given PO; Other Names: 4',5, 7-Trihydroxyisoflavone Genestein Genisteol Prunetol ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies
Placebo Comparator: Arm II (placebo) 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; Correlative studies; Other: Pharmacological Study; Correlative studies; Other: Placebo; Given PO; Other Names: placebo therapy PLCB sham therapy

Outcome Measures

Primary Outcome Measures

1. Tissue Levels of Calcitriol Between the Placebo and Cholecalciferol/Genistein Arms [up to Day 35]

   This is a measure of calcitriol in prostate tissue comparing placebo and cholecalciferol/genistein

2. Detectability of Calcitriol Levels in Tissue Between the Placebo and Cholecalciferol/Genistein Arms [up to 35 days]

   To identify the amount of Calcitriol that is found in the tissue comparing Placebo and Cholecalciferol/Genistein

Secondary Outcome Measures

1. Levels of Calcidiol in the Participants Serum [Baseline and up to day 35]

   This is measuring the amount of Calcidiol that was found in the participants blood Serum at baseline and end of study

2. Levels of Calcitriol in Participants Serum [baseline and Up to Day 35]

   This is measuring the amount of Calcitriol that was found in the participants blood Serum at baseline and end of study.

3. PBMC CYP mRNA Expression of CYP24 [Baseline and Up to Day 35]

   This is a measure of expression of CYP24 in comparing placebo to Cholecalciferol/genistein.

4. PBMC CYP mRNA Expression of CYP27B1 [Up to Day 35]

   This is a measure of expression of CYP27B1 in comparing placebo to Cholecalciferol/genistein.

5. Total PSA in Serum [at Baseline and up to Day 35]

   This is a measure of the concentration of PSA in the blood serum at baseline and at the end of study.

6. Serum Calcium Levels at Baseline and Pre-Surgery [Baseline and Day 35]

   This is a measurement of calcium in the Blood serum at baseline and at the end of the study.

7. Total IGF-1 in Serum at Baseline and Pre-Surgery [Baseline and up to Day 35]

   This is measuring the concentration of the Biomarker IGF-1 in blood serum at Baseline and at the end of the study.

8. Total IGF-2 in Serum at Baseline and Pre-Surgery [Baseline and Up to Day 35]

   This is measuring the concentration of the Biomarker IGF-2 in blood serum at Baseline and at the end of the study

9. Total IGFBP-3 in Serum at Baseline and Pre-Surgery [Baseline and Up to Day 35]

   This is measuring the concentration of the Biomarker IGFBP-3 in blood serum at Baseline and at the end of the study.

10. Total PTH in Serum at Baseline and Pre-Surgery [Baseline and Up to Day 35]

    This is measuring the concentration of the Biomarker PTH in blood serum at Baseline and at the end of the study

11. Immunohistochemistry Measurements in Benign Prostate Tissue (BPT) [Up to Day 35]

    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.

12. Immunohistochemistry Measurements in Prostate Cancer Tissue (PCA) [Up to day Day 35]

    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.

13. Percent of Participants With CYP24 and CYP27B1 SNPs (DNA From Paxgene) [up to Day 35]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital	Baltimore	Maryland	United States	21231
3	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
4	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
5	Minneapolis Veterans Medical Center	Minneapolis	Minnesota	United States	55417
6	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota	United States	55455
7	University of Rochester	Rochester	New York	United States	14642
8	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
9	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
10	Urology San Antonio Research PA	San Antonio	Texas	United States	78229
11	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Jarrard, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01325311
• Other Study ID Numbers: NCI-2013-00451; NCI-2013-00451; UWI09-14-01; CDR0000698228; CO-10805; CO 10805; UWI09-14-01; N01CN35153; P30CA014520
• First Posted: Mar 29, 2011
• Last Update Posted: Aug 3, 2016
• Last Verified: Jun 1, 2016

• Additional relevant MeSH terms: Prostatic Neoplasms; Vitamin D; Cholecalciferol; Genistein

Study Results

Participant Flow

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Period Title: Overall Study
STARTED	8	7
COMPLETED	8	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)	Total
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies	Total of all reporting groups
Overall Participants	8	7	15
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 75%	5 71.4%	11 73.3%
>=65 years	2 25%	2 28.6%	4 26.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.75 (4.50)	62.14 (4.26)	61.40 (4.29)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	7 100%	15 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 12.5%	0 0%	1 6.7%
Not Hispanic or Latino	7 87.5%	7 100%	14 93.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	7 100%	15 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	7 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Tissue Levels of Calcitriol Between the Placebo and Cholecalciferol/Genistein Arms
Description	This is a measure of calcitriol in prostate tissue comparing placebo and cholecalciferol/genistein
Time Frame	up to Day 35

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	7
Mean (Standard Deviation) [ng/mL]	0.045 (0.127)	0.057 (0.150)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm II (Placebo), Arm I (Cholecalciferol, Genistein)
	Comments	Using the Student t-test. If the normality assumption is tenuous, an appropriate transformation of the data such as logarithm will be considered for Student t-test or a nonparametric test such as Wilcoxon rank-sum test will be used for comparison.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.922
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Levels of Calcidiol in the Participants Serum
Description	This is measuring the amount of Calcidiol that was found in the participants blood Serum at baseline and end of study
Time Frame	Baseline and up to day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant in Arm 1 was not analyzed for this Outcome.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	20.5 (5.5)	24.5 (9.3)
Pre-Surgery	19.2 (5.1)	27.3 (10.0)

3. Primary Outcome

Title	Detectability of Calcitriol Levels in Tissue Between the Placebo and Cholecalciferol/Genistein Arms
Description	To identify the amount of Calcitriol that is found in the tissue comparing Placebo and Cholecalciferol/Genistein
Time Frame	up to 35 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	7
Undetectable	7 87.5%	6 85.7%
Detectable	1 12.5%	1 14.3%

4. Secondary Outcome

Title	Levels of Calcitriol in Participants Serum
Description	This is measuring the amount of Calcitriol that was found in the participants blood Serum at baseline and end of study.
Time Frame	baseline and Up to Day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant in Arm 1 was not analyzed for this Outcome.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	0.5 (0.1)	0.5 (0.2)
Pre-Surgery	0.5 (0.7)	0.1 (0.4)

5. Secondary Outcome

Title	PBMC CYP mRNA Expression of CYP24
Description	This is a measure of expression of CYP24 in comparing placebo to Cholecalciferol/genistein.
Time Frame	Baseline and Up to Day 35

Outcome Measure Data

Analysis Population Description

Due to sample two participant in Arm I and 2 participants in Arm II were not analyzed for this Outcome.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	6	5
Geometric Mean (Standard Deviation) [Ratio to Baseline]	3.054 (3.997)	2.202 (4.071)

6. Secondary Outcome

Title	PBMC CYP mRNA Expression of CYP27B1
Description	This is a measure of expression of CYP27B1 in comparing placebo to Cholecalciferol/genistein.
Time Frame	Up to Day 35

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	7
Geometric Mean (Standard Deviation) [Ratio to Baseline]	1.656 (2.628)	2.389 (3.511)

7. Secondary Outcome

Title	Total PSA in Serum
Description	This is a measure of the concentration of PSA in the blood serum at baseline and at the end of study.
Time Frame	at Baseline and up to Day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant in Arm I was not analyzed for this Outcome.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	8.7 (7.3)	6.3 (1.7)
Day 35	8.3 (6.7)	5.8 (2.1)

8. Secondary Outcome

Title	Serum Calcium Levels at Baseline and Pre-Surgery
Description	This is a measurement of calcium in the Blood serum at baseline and at the end of the study.
Time Frame	Baseline and Day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant in Arm I was not analyzed for this Outcome.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	10.5 (0.4)	11.3 (1.8)
Day 35	10.8 (0.9)	10.9 (0.9)

9. Secondary Outcome

Title	Total IGF-1 in Serum at Baseline and Pre-Surgery
Description	This is measuring the concentration of the Biomarker IGF-1 in blood serum at Baseline and at the end of the study.
Time Frame	Baseline and up to Day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant in Arm I was not analyzed for this Outcome.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	64.2 (11.5)	66.3 (12.8)
Day 35	60.6 (17.9)	74.6 (14.0)

10. Secondary Outcome

Title	Total IGF-2 in Serum at Baseline and Pre-Surgery
Description	This is measuring the concentration of the Biomarker IGF-2 in blood serum at Baseline and at the end of the study
Time Frame	Baseline and Up to Day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant in Arm 1 was not analyzed.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	770.4 (333.4)	805.9 (193.5)
Pre-Surgery	605.0 (175.4)	858.8 (112.7)

11. Secondary Outcome

Title	Total IGFBP-3 in Serum at Baseline and Pre-Surgery
Description	This is measuring the concentration of the Biomarker IGFBP-3 in blood serum at Baseline and at the end of the study.
Time Frame	Baseline and Up to Day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant from Arm 1 was not analyzed.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	1838.9 (887.3)	2004.5 (309.8)
Day 35	1667.5 (788.9)	1843.4 (443.3)

12. Secondary Outcome

Title	Total PTH in Serum at Baseline and Pre-Surgery
Description	This is measuring the concentration of the Biomarker PTH in blood serum at Baseline and at the end of the study
Time Frame	Baseline and Up to Day 35

Outcome Measure Data

Analysis Population Description

Due to sample one participant in Arm I was not analyzed.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	6
Baseline	143.4 (26.5)	144.8 (37.8)
Pre-Surgery	151.1 (25.8)	136.5 (72.9)

13. Secondary Outcome

Title	Immunohistochemistry Measurements in Benign Prostate Tissue (BPT)
Description	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.
Time Frame	Up to Day 35

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	7
AR (Nucleus)	-0.362 (0.294)	0.414 (1.301)
VDR (Cytoplasm)	-0.451 (0.410)	0.515 (1.179)
p21 (Nucleus)	-0.085 (1.070)	0.097 (0.900)
PGE2 (Cytoplasm)	-0.161 (1.023)	0.184 (0.934)
TUNEL Pos (Nucleus)	-0.168 (0.842)	0.192 (1.122)
Caspase 3 (Cytoplasm)	-0.308 (0.659)	0.352 (1.178)
PSMA (Cytoplasm)	0.025 (1.231)	-0.029 (0.630)
IGF-1 (Cytoplasm)	-0.295 (0.607)	0.337 (1.220)
IGF-2 (Cytoplasm)	-0.335 (0.763)	0.383 (1.081)
Akt (Nucleus)	-0.316 (0.618)	0.361 (1.198)
pAkt (Nucleus)	-0.114 (0.920)	0.131 (1.068)
Akt (Cytoplasm)	-0.249 (0.766)	0.284 (1.142)
pAkt (Cytoplasm)	-0.053 (1.004)	0.061 (0.991)

14. Secondary Outcome

Title	Immunohistochemistry Measurements in Prostate Cancer Tissue (PCA)
Description	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.
Time Frame	Up to day Day 35

Outcome Measure Data

Analysis Population Description

Due to sample in Arm II one participants data was not analyzed.

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	7	7
AR (Nucleus)	-0.563 (0.481)	0.563 (1.015)
VDR (Cytoplasm)	-0.281 (0.657)	0.281 (1.177)
p21 (Nucleus)	-0.185 (0.489)	0.185 (1.296)
PGE2 (Cytoplasm)	-0.135 (0.969)	0.135 (1.009)
TUNEL Pos (Nucleus)	-0.363 (0.664)	0.363 (1.119)
Caspase 3 (Cytoplasm)	-0.103 (0.742)	0.103 (1.194)
PSMA (Cytoplasm)	-0.210 (0.966)	0.210 (0.982)
IGF-1 (Cytoplasm)	0.155 (1.027)	-0.155 (0.943)
IGF-2 (Cytoplasm)	0.443 (1.102)	-0.443 (0.572)
Akt (Nucleus)	-0.309 (0.903)	0.309 (0.981)
pAkt (Nucleus)	-0.291 (0.325)	0.291 (1.302)
Akt (Cytoplasm)	-0.379 (0.785)	0.379 (1.024)
pAkt (Cytoplasm)	-0.365 (0.377)	0.365 (1.244)

15. Secondary Outcome

Title	Percent of Participants With CYP24 and CYP27B1 SNPs (DNA From Paxgene)
Time Frame	up to Day 35

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm II (Placebo)	Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO	Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	8	7
rs2209314- T/C	37.5 468.8%	42.86 612.3%
rs2209314- T/T	62.5 781.3%	57.14 816.3%
rs2248359- C/C	37.5 468.8%	42.86 612.3%
rs2248359- C/T	37.5 468.8%	57.14 816.3%
rs2248359- T/T	25 312.5%	0 0%
rs2296241- A/A	37.5 468.8%	14.29 204.1%
rs2296241- A/G	35.5 443.8%	71.43 1020.4%
rs2296241- G/G	25 312.5%	14.29 204.1%
rs2762939- C/G	37.5 468.8%	28.57 408.1%
rs2762939- G/G	62.5 781.3%	71.43 1020.4%
rs927650- C/C	0 0%	71.43 1020.4%
rs927650- C/T	50 625%	14.29 204.1%
rs927650- T/T	50 625%	14.29 204.1%
rs703842- A/A	50 625%	14.29 204.1%
rs703842- A/G	37.5 468.8%	71.43 1020.4%
rs703842- G/G	12.5 156.3%	14.29 204.1%

Adverse Events

Arm/Group Title	Arm II (Placebo)		Arm I (Cholecalciferol, Genistein)
Arm/Group Description	Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO		Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy. Cholecalciferol: Given PO Genistein: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
All Cause Mortality
	Arm II (Placebo)		Arm I (Cholecalciferol, Genistein)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm II (Placebo)		Arm I (Cholecalciferol, Genistein)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Arm II (Placebo)		Arm I (Cholecalciferol, Genistein)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/8 (50%)		5/7 (71.4%)
Endocrine disorders
hyperthyriodism	1/8 (12.5%)	1	0/7 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/8 (0%)	0	2/7 (28.6%)	2
diarrhea	0/8 (0%)	0	2/7 (28.6%)	2
General disorders
fatigue	1/8 (12.5%)	1	0/7 (0%)	0
pain	0/8 (0%)	0	1/7 (14.3%)	1
Infections and infestations
sinusitis	0/8 (0%)	0	1/7 (14.3%)	2
Investigations
blood bilirubin increased	1/8 (12.5%)	1	0/7 (0%)	0
increased serum chloride	1/8 (12.5%)	1	0/7 (0%)	0
platelet count decreased	0/8 (0%)	0	1/7 (14.3%)	1
Metabolism and nutrition disorders
hyperglycemia	1/8 (12.5%)	1	0/7 (0%)	0
hypophosphatemia	1/8 (12.5%)	1	0/7 (0%)	0
Nervous system disorders
sinus pain	0/8 (0%)	0	1/7 (14.3%)	2
Respiratory, thoracic and mediastinal disorders
allergic rhinitis	0/8 (0%)	0	1/7 (14.3%)	1
calcified lung nodule-right ct scan	1/8 (12.5%)	1	0/7 (0%)	0
Vascular disorders
hypertension	1/8 (12.5%)	1	2/7 (28.6%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.