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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01325311
First received: March 23, 2011
Last updated: June 20, 2016
Last verified: June 2016
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tissue Levels of Calcitriol Between the Placebo and Cholecalciferol/Genistein Arms [ Time Frame: up to Day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: up to 35 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and up to day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and Up to Day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Up to Day 35 ] [ Designated as safety issue: No ]
    This is a measure of expression of CYP24 in comparing placebo to Cholecalciferol/genistein.

  • PBMC CYP mRNA Expression of CYP27B1 [ Time Frame: Up to Day 35 ] [ Designated as safety issue: No ]
    This is a measure of expression of CYP27B1 in comparing placebo to Cholecalciferol/genistein.

  • Total PSA in Serum [ Time Frame: at Baseline and up to Day 35 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and up to Day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Up to Day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Up to Day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Up to Day 35 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to Day 35 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Up to day Day 35 ] [ Designated as safety issue: No ]

    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) [ Time Frame: up to Day 35 ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: December 2011
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01325311

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

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01325311     History of Changes
Other Study ID Numbers: NCI-2013-00451  NCI-2013-00451  UWI09-14-01  CDR0000698228  CO-10805  CO 10805  UWI09-14-01  N01CN35153  P30CA014520 
Study First Received: March 23, 2011
Results First Received: December 24, 2015
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Cholecalciferol
Genistein
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Anticarcinogenic Agents
Protective Agents
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 26, 2016