Clinical trial NCT01325311: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Adenocarcinoma
Stage I Prostate Cancer
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2011-03-29
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Tissue Levels of Calcitriol Between the Placebo and Cholecalciferol/Genistein Arms
timeFrame: up to Day 35
measure: Detectability of Calcitriol Levels in Tissue Between the Placebo and Cholecalciferol/Genistein Arms
timeFrame: up to 35 days
Secondary outcomes:
measure: Levels of Calcidiol in the Participants Serum
timeFrame: Baseline and up to day 35
measure: Levels of Calcitriol in Participants Serum
timeFrame: baseline and Up to Day 35
measure: PBMC CYP mRNA Expression of CYP24
timeFrame: Baseline and Up to Day 35
measure: PBMC CYP mRNA Expression of CYP27B1
timeFrame: Up to Day 35
measure: Total PSA in Serum
timeFrame: at Baseline and up to Day 35
measure: Serum Calcium Levels at Baseline and Pre-Surgery
timeFrame: Baseline and Day 35
measure: Total IGF-1 in Serum at Baseline and Pre-Surgery
timeFrame: Baseline and up to Day 35
measure: Total IGF-2 in Serum at Baseline and Pre-Surgery
timeFrame: Baseline and Up to Day 35
measure: Total IGFBP-3 in Serum at Baseline and Pre-Surgery
timeFrame: Baseline and Up to Day 35
measure: Total PTH in Serum at Baseline and Pre-Surgery
timeFrame: Baseline and Up to Day 35
measure: Immunohistochemistry Measurements in Benign Prostate Tissue (BPT)
timeFrame: Up to Day 35
measure: Immunohistochemistry Measurements in Prostate Cancer Tissue (PCA)
timeFrame: Up to day Day 35
measure: Percent of Participants With CYP24 and CYP27B1 SNPs (DNA From Paxgene)
timeFrame: up to Day 35
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis Veterans Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: San Antonio
country: United States
facility: Urology San Antonio Research PA
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: David Jarrard
role: PRINCIPAL_INVESTIGATOR
References: