Phase II Clinical Trial of Purified Isoflavones in Prostate Cancer: Comparing Safety, Effectiveness

Study Overview
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Brief Summary
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The purpose of our study is to recruit and treat 96 men diagnosed with prostate cancer and scheduled for a prostatectomy with a capsule form of either purified isoflavones or placebo for a 3-6 week period to see if we can slow down the rate of prostate cancer growth. A placebo is a pill or something that looks like the medicine that is being studied but has no active medicine in it. We also want to see if taking purified isoflavones is safe and if it reduces lower urinary tract symptoms. In addition, we want to study if purified isoflavones are able to slow the progression of prostate cancer, and the mechanism of action of purified isoflavones. If the safety and the effects of purified isoflavones on slowing down the progression of prostate cancer is shown in our study, this will also be a safe way of treating men who are at high risk of prostate cancer, so that we can prevent prostate cancer in the future.

Detailed Description
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Patients will need to take two (2) capsules daily, one with their breakfast and one with their dinner. On the day prior or the day that patients are coming in for their pre-operative surgery blood work, we ask that they take the second dose with lunch, if their appointment is in the afternoon. At the start of the study and at the end of the study (3-6 weeks), patients will undergo interviews, complete questionnaires, and have lab tests to determine if this drug is effective to reduce progression of prostate cancer and is safe to use. Patients will also receive a multivitamin/mineral supplement for the 3-6 weeks that they are on this study and will be required to take one (1) every day. It is required that patients not take any other vitamin/mineral or herbal preparation containing isoflavones and avoid eating or drinking soy products. We anticipate that most patients will be scheduled for a prostatectomy 3-6 weeks (+/- 3 days) from start of study agent. In addition to their first visit, patients will be required to come in the day of the surgery for prostatectomy.

Official Title
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Phase II Clinical Trial of Purified Isoflavones in Prostate Cancer: Comparing Safety, Effectiveness and Mechanism of Action Between African American and Caucasian Men

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Purified isoflavones
* Drug: Methyl cellulose blend


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of localized prostate cancer (PCa), based on pathological assessment from biopsy specimens No prior or current therapy for PCa or history of cancer except non-melanoma skin cancer Scheduled for prostatectomy between 3- 6 weeks (+/-3 days) after start of study agent No known history of hepatic or renal disease (LFTs (SGOT/SGPT) > 5.0 x upper limit of normal as evidenced by impairment of baseline laboratory values, Actual creatinine clearance of >60 utilizing the Cockcroft-Gault formula (1976), which employs creatinine measurements and a patient's weight to predict the clearance. The constant is 1.23 for men. Omnivorous diet No evidence of prostatitis or urinary tract infection Able and willing to give written informed consent Currently not using or willing to discontinue any nutritional supplements that contain soy or soy isoflavones Not allergic to study supplements Not on antibiotics Men who do not consume more than 3 - 4 oz. of soy or soy products per week Not taking steroid hormones or medications which have known impact on prostatic specific antigen (PSA) Health status cleared by primary MD or urologist Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Exclusion Criteria: Prior history of prostate cancer; Current or prior history of other malignancies (exceptions include nonmelanoma skin cancer or other cancer with no evidence of tumor recurrence five years after definitive treatment) History of renal or hepatic disease, including history of hepatitis B, C or delta as evidenced by impairment of baseline laboratory values Participation in any other investigational study or use of any other investigational agents within 30 days of study entry History of allergic reactions attributed to soy isoflavones or other compounds of similar chemical or biologic composition to Novasoy 400® or the inactive components present in the purified isoflavone and placebo capsules Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any psychological, familial, sociological or other concomitant condition that would not allow adequate compliance with the study protocol Only African American (a person having origins in any of the black racial groups of Africa) and Caucasian (a person having origins in any of the original people of Europe, Middle East, or North Africa) men, as defined by the NIH, will be included in this study. Since this is an investigation targeting men with PCa, women are not eligible for the study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Purified Isoflavones<br>Soy-based isoflavone concentrate with methyl cellulose blend filler. 40 mg daily. | Drug: Purified isoflavones<br>* Soy-based isoflavone concentrate with methyl cellulose blend filler - Take 2 capsules daily<br>* Other names: Avicel PH105;|
| Placebo Comparator: Methyl cellulose blend<br>Placebo. | Drug: Methyl cellulose blend<br>* Placebo - Take 2 capsules daily<br>* Other names: Avicel PH105;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Change in Percent Ki-67 From Baseline | Efficacy: Change in percent Ki-67 evaluated in prostate cancer (PCa) tissue specimens after 3-6 weeks of intervention with purified isoflavones (40 mg daily) vs. Placebo. | Baseline to post intervention - up to 6 weeks | 
| Number of Toxicity Events by Final Attribution and Treatment Arm | Safety: Incidence of Adverse Events (AEs) occurring during intervention with either 20 mg purified isoflavones bid or placebo. Serious Adverse Event (SAEs) and other Adverse Event (AE) details are also reported in the Adverse Event sections. | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers of Disease Progression - Serum PSA | Median change from baseline to post intervention: Prostatic specific antigen (PSA). All Participants (ALL); Caucasian Men only (CM only); African American Men only (AAM only). | Up to 6 weeks | 
| Change in Plasma Concentrations of Isoflavone | Plasma concentrations of isoflavone: Genistein from baseline to post intervention by study arm. | Up to 6 weeks | 
| Biomarkers of Disease Progression - Estradiol | Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:). | Up to 6 weeks | 
| Biomarkers of Disease Progression - Free Testosterone | Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:). | Up to 6 weeks | 
| Biomarkers of Disease Progression - Insulin Like Growth Factor (IGF) Binding Protein -3 | Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:). | Up to 6 weeks | 
| Biomarkers of Disease Progression - IGF-1 | Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:). | Up to 6 weeks | 
| Biomarkers of Disease Progression - Sex Hormone-binding Globulin (SHBG) | Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:). | Up to 6 weeks | 
| Biomarkers of Disease Progression - Total Testosterone | Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:). | Up to 6 weeks |