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

• Incidence of Change in Percent Ki-67 [ Time Frame: 4 - 6 weeks per participant (+/- 3 days) ] [ Designated as safety issue: No ]
  Efficacy: Change in percent Ki-67 evaluated in prostate cancer tissue specimens after 4-6 weeks of intervention with purified isoflavones (40 mg daily) vs. Placebo.
• Incidence of Adverse Events (AEs) [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: Yes ]
  Safety: Incidence and severity of AEs occurring during intervention with either 20 mg purified isoflavones bid or placebo.

• Efficacy: Change in percent Ki-67 evaluated in prostate cancer tissue specimens after 4-6 weeks of intervention with purified isoflavones (40 mg daily) vs. Placebo. [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: No ]
• Safety: Incidence and severity of AEs occurring during intervention with either 20 mg purified isoflavones bid or placebo. [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: Yes ]

• Biomarkers of Disease Progression. [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: No ]
  Biomarkers of disease progression: Serum steroid hormones, prostatic specific antigen (PSA0, apoptotic index, Tumor Volume (TV), Gleason Score (GS); Symptoms including Lower Urinary Tract Symptoms (LUTS).
• Expression Levels of Isoflavone Participants [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: No ]
  Mechanism: To determine if purified isoflavones at a dose of 40 mg daily (20 mg bid) vs. placebo results in decreased expression of the androgen receptor and increased expression levels of forkhead box O1 (FOXO1) and its target genes from baseline to prostatectomy in prostate cancer patients and whether the treatment effect of the study agent in the AR-FOXO axis is more profound in African American patients as compared to the Caucasian group and correlates inversely with ERα/ERβ ratio.

• Drug effect measurements in tissue samples [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: No ]
• To determine if purified isoflavones (40 mg daily) vs. placebo results in decreased expression of the androgen receptor and increased expression levels of FOXO1 and its target genes from baseline to prostatectomy in prostate cancer patients [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: No ]
• Whether the treatment effect of the study agent in the AR-FOXO axis is more profound in African American patients as compared to the Caucasian group and correlates inversely with ERα/ERβ ratio [ Time Frame: 4 - 6 weeks per participant ] [ Designated as safety issue: No ]

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 4-6 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.

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 (4-6 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 4-6 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 4-6 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.

• Drug: Purified isoflavones
  Soy-based isoflavone concentrate with methyl cellulose blend filler - Take 2 capsules daily
  Other Names:

  • Novasoy 400
  • Avicel PH105
• Drug: Methyl cellulose blend
  Placebo - Take 2 capsules daily
  Other Name: Avicel PH105

• Active Comparator: Purified Isoflavones
  Soy-based isoflavone concentrate with methyl cellulose blend filler. 40 mg daily.
  Intervention: Drug: Purified isoflavones
• Placebo Comparator: Methyl cellulose blend
  Placebo.
  Intervention: Drug: Methyl cellulose blend

Inclusion Criteria:

• Diagnosis of localized CaP, based on pathological assessment from biopsy specimens
• No prior or current therapy for CaP or history of cancer except non-melanoma skin cancer
• Scheduled for prostatectomy between 4- 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 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 CaP, women are not eligible for the study.