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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Adenocarcinoma; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Pharmacological Study; Drug: Cholecalciferol; Drug: Genistein

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center-Fairview
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis Veterans Medical Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio Research PA
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Cholecalciferol; Given PO; Other Names: Vitamin D3; 9,10-Secocholesta-5,7,10(19)-trien-3-ol; Calciol; Delsterol; Drug: Genistein; Given PO; Other Names: Genestein; 4',5, 7-Trihydroxyisoflavone; Genisteol; Prunetol
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: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Other: Pharmacological Study; Correlative studies

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David Jarrard, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: March 23, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (ESTIMATE): March 29, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 3, 2016
• Last Update Submitted That Met QC Criteria: June 20, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens, Non-Steroidal; Estrogens; Micronutrients; Protein Kinase Inhibitors; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Anticarcinogenic Agents; Phytoestrogens; Vitamin D; Cholecalciferol; Genistein
• Other Study ID Numbers: NCI-2013-00451 (REGISTRY: CTRP (Clinical Trial Reporting Program)); P30CA014520 (U.S. NIH Grant/Contract); N01CN35153 (U.S. NIH Grant/Contract); UWI09-14-01 (OTHER: DCP); CDR0000698228; CO-10805; CO 10805 (OTHER: University of Wisconsin Hospital and Clinics)