Biomarkers of Sulforaphane/Broccoli Sprout Extract in Prostate Cancer

Study Overview
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Brief Summary
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This study will test whether oral intake of a dietary supplement called BroccoMax®, which is a special blend of broccoli extract containing a chemical called sulforaphane (hereafter abbreviated as SFN), may result in changes in chemicals that feed prostate cancer. BroccoMax® is available over the counter.

Detailed Description
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Eligible subjects will be randomly assigned to either BroccoMax® or placebo arm with a 1:1 randomization. Each subject will be given BroccoMax® equivalent to 4 weeks supply. Following randomization, subjects will begin to take four study tablets (BroccoMax® or placebo) in the morning with breakfast and four tablets in the evening with dinner. The eight BroccoMax® tablets will provide a daily internal dose of 64 mg of SFN. Baseline evaluation will be 28 days before scheduled prostatectomy, the same day of study drug dispensation, and will include. Data collection on patient's medical history (which includes age, cancer history, review of medications, food intolerances and food habits), and concomitant medications. Physical exam including height and weight measurements. Blood (approximately 15 mL) will be collected in Serum Separator Tube-tiger tubes (SST)for determination of SFN and its metabolite levels and for biomarker analyses. Spot urine collection (15 mL) for measuring SFN and its metabolite levels. Four-week supply of study drug (BroccoMax® or Placebo) dispensation Day 28 ± 3 days (End of study evaluation) Physical exam including height and weight measurements Blood (approximately 15 mL) will be collected in SST-tiger tubes for determination of SFN and its metabolite levels and for biomarker analyses. Spot urine collection (15 mL) for measuring SFN and its metabolite levels. Adverse event assessment. A portion of the prostate tumor after surgical resection will be fresh frozen in liquid nitrogen. After pathological assessment is complete, tumor blocks or slides (6 or more) will be requested by the clinical research coordinator from the Health Sciences Tissue Bank of the University of Pittsburgh for biomarker analyses. Post-Treatment Follow-Up All study participants will have routine follow-up as determined by their treating urologist and/ or medical oncologist. This usually occurs 6 ± 2 weeks post-surgery and every 3 months thereafter. These are considered standard of care visits. The patient chart will be reviewed for their history and physical findings at these visits.

Official Title
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Biomarkers of Sulforaphane/Broccoli Sprout Extract in Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: BroccoMax®
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men ≥ 18 years of age scheduled to undergo radical prostatectomy as standard of care for a diagnosis of prostate adenocarcinoma. Subjects willing to take oral placebo or BroccoMax® pills (4 capsules twice daily after breakfast and dinner) on a daily basis for 4 weeks prior to prostatectomy. Subjects have the ability to swallow BroccoMax® or placebo pills. Subjects in good health per investigator evaluation with liver enzyme and blood count values within the following ranges: White blood cells ≥ 3,000/mL Total bilirubin ≤ 1.5 x Upper Limits of Normal (ULN) Aspartate Aminotransferase (AST (SGOT))/ Alanine Aminotransferase (ALT (SGPT)) ≤ 2.5 x ULN Blood Urea Nitrogen (BUN) and serum creatinine ≤ 1.5 x ULN Subjects willing to abstain from dietary sources of glucosinolates and isothiocyanates (see Appendix) for the duration of the study (4 weeks) Subjects must be fully informed of the investigational nature of this study and must sign a written informed consent in accordance within institutional and regulatory guidelines Exclusion Criteria: Subjects ineligible to undergo prostatectomy due to co-morbidities. Subjects with a second malignancy or any other cancer at least 3 years following definitive treatment with no evidence of disease, except for adequately treated basal cell or squamous cell skin cancer. Subjects with malabsorption issues or gastrointestinal ailments than can interfere with the ability to adequately absorb SFN. Subjects with prior or concurrent androgen deprivation therapy with Luteinizing hormone-releasing hormone (LHRH) agonist or antagonists Subjects taking any other investigational agent, dietary supplement or herbal supplement or participating in clinical studies involving investigational agents Subjects with clinically significant comorbid diseases including active infection, uncontrolled angina, New York Heart Assoc. (NYHA) class III or IV heart failure, uncontrolled or uncontrollable hypertension, severe diabetes with complications, chronic liver disease. Subjects with prior history of known intolerance or allergic reactions attributed to cruciferous vegetables or specific fillers used in the placebo.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind randomized placebo controlled design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BroccoMax®<br>Following randomization, subjects will begin to take four BroccoMax® tablets in the morning with breakfast and four tablets in the evening with dinner. The eight BroccoMax® tablets will provide a daily internal dose of 64 mg of SFN. | Dietary Supplement: BroccoMax®<br>* Nutraceutical neoadjuvant<br>|
| Placebo Comparator: Placebo<br>Following randomization, subjects will begin to take four placebo tablets in the morning with breakfast and four tablets in the evening with dinner. | Other: Placebo<br>* control<br>* Other names: Microcrystalline cellulose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palmitic Acid Reduction | Change in serum levels of palmitic acid (the primary free fatty acid) in subjects treated with BroccoMax® compared to placebo. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety of BroccoMax® (side effects or adverse events) | Assessing any side effects or adverse events that could be associated with the oral intake of BroccoMax® | 2 months | 
| Serum SFN levels | Compare the levels of SFN and its metabolites in serum at day 14 and week 4 to baseline | 4 weeks | 
| Urine SFN levels | Compare the levels of SFN and its metabolites in urine at day 14 and week 4 to baseline. | 4 weeks | 
| Prostate adenocarcinoma SFN level | Evaluate the SFN and its metabolites in the prostate/ prostate adenocarcinoma tissue. | Week 4 | 
| Mean proliferative index (Ki-67) and apoptotic marker (TUNEL) in prostate adenocarcinoma sections | Evaluate the biomarkers of the collected tissue. | Week 4 | 
| Evaluation of Prostate adenocarcinoma tissue by immunohistochemistry. | Prostate adenocarcinoma expression of acetyl-Coenzyme A carboxylase 1 (ACC1), fatty acid synthase (FASN), carnitine palmitoyltransferase1A (CPT1A), androgen receptor (AR), phosphatase and tensin homolog (PTEN), sterol regulatory binding protein 1 (SREBP-1) and c-Myc by immunohistochemistry (IHC) | Week 4 | 
| Evaluation of serum levels of fatty acid metabolism intermediates. | Evaluate Serum levels of Acetyl-Coenzyme A, Malonyl-Coenzyme A, total phospholipids, adenosine triphosphate (ATP), and global lipidemic | Weeks 2 and 4. | 
| Evaluation of prostate adenocarcinoma levels of fatty acid metabolism intermediates | Evaluate prostate adenocarcinoma levels of Acetyl-Coenzyme A, Malonyl-Coenzyme A, total phospholipids, ATP, and global lipidemic | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostatectomy