search
Back to results

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

Primary Purpose

Prostate Adenocarcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cholecalciferol
Genistein
Laboratory Biomarker Analysis
Pharmacological Study
Placebo
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham Cancer Center
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Lahey Hospital and Medical Center
  • Minneapolis Veterans Medical Center
  • University of Minnesota Medical Center-Fairview
  • University of Rochester
  • University of Oklahoma Health Sciences Center
  • Carolina Urologic Research Center
  • Urology San Antonio Research PA
  • University of Wisconsin Hospital and Clinics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (cholecalciferol, genistein)

Arm II (placebo)

Arm Description

Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy.

Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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
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.
PBMC CYP mRNA Expression of CYP24
This is a measure of expression of CYP24 in comparing placebo to Cholecalciferol/genistein.
PBMC CYP mRNA Expression of CYP27B1
This is a measure of expression of CYP27B1 in comparing placebo to Cholecalciferol/genistein.
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.
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.
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.
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
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.
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
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.
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.
Percent of Participants With CYP24 and CYP27B1 SNPs (DNA From Paxgene)

Full Information

First Posted
March 23, 2011
Last Updated
June 20, 2016
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01325311
Brief Title
Cholecalciferol and Genistein Before Surgery in Treating Patients With Early Stage Prostate Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Adenocarcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (cholecalciferol, genistein)
Arm Type
Experimental
Arm Description
Patients receive cholecalciferol PO on day 1 and genistein PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO on day 1 and placebo PO QD on days 1-21 or 1-28. Patients then undergo prostatectomy.
Intervention Type
Drug
Intervention Name(s)
Cholecalciferol
Other Intervention Name(s)
9,10-Secocholesta-5,7,10(19)-trien-3-ol, Calciol, Delsterol, Vitamin D3
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Genistein
Other Intervention Name(s)
4',5, 7-Trihydroxyisoflavone, Genestein, Genisteol, Prunetol
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given PO
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
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
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
Title
Percent of Participants With CYP24 and CYP27B1 SNPs (DNA From Paxgene)
Time Frame
up to Day 35

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Jarrard
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Lahey Hospital and Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
Minneapolis Veterans Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55417
Country
United States
Facility Name
University of Minnesota Medical Center-Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Facility Name
Urology San Antonio Research PA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs