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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01036321

Enrollment

Registered

2009-12-21

Start date

2009-12-11

Completion date

2018-04-16

Last updated

2019-08-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

Brief summary

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

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.

Interventions

DRUGPurified isoflavones

Soy-based isoflavone concentrate with methyl cellulose blend filler - Take 2 capsules daily

DRUGMethyl cellulose blend

Placebo - Take 2 capsules daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

MALE

Age

30 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Median Change in Percent Ki-67 From Baseline	Baseline to post intervention - up to 6 weeks	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.
Number of Toxicity Events by Final Attribution and Treatment Arm	Up to 6 weeks	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.

Secondary

Measure	Time frame	Description
Biomarkers of Disease Progression - Estradiol	Up to 6 weeks	Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Biomarkers of Disease Progression - Free Testosterone	Up to 6 weeks	Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Biomarkers of Disease Progression - Insulin Like Growth Factor (IGF) Binding Protein -3	Up to 6 weeks	Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Biomarkers of Disease Progression - Serum PSA	Up to 6 weeks	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).
Biomarkers of Disease Progression - Sex Hormone-binding Globulin (SHBG)	Up to 6 weeks	Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Biomarkers of Disease Progression - Total Testosterone	Up to 6 weeks	Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Biomarkers of Disease Progression - IGF-1	Up to 6 weeks	Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Change in Plasma Concentrations of Isoflavone	Up to 6 weeks	Plasma concentrations of isoflavone: Genistein from baseline to post intervention by study arm.

Countries

United States

Participant flow

Recruitment details

Participants were enrolled from January 2010 through May 2014 at three sites in Florida.

Pre-assignment details

75 were consented and were further screened for final eligibility. 3 were ineligible and 1 withdrew after screening, before randomization. 71 were randomized. 1 was ineligible after randomization.

Participants by arm

Arm	Count
Active Comparator: Purified Isoflavones Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.	36
Placebo Comparator: Methyl Cellulose Blend Placebo: Methyl cellulose blend - 2 capsules daily.	35
Total	71

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	1
Overall Study	Ineligible after randomization	0	1
Overall Study	Withdrawal by Subject	3	2

Baseline characteristics

Characteristic	Active Comparator: Purified Isoflavones	Total	Placebo Comparator: Methyl Cellulose Blend
Age, Continuous	58.8 years STANDARD_DEVIATION 7.5	58.9 years STANDARD_DEVIATION 7.4	59.1 years STANDARD_DEVIATION 7.4
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	7 Participants	15 Participants	8 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) White	28 Participants	53 Participants	25 Participants
Region of Enrollment United States	36 participants	71 participants	35 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	36 Participants	71 Participants	35 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	27 / 36	24 / 35
serious Total, serious adverse events	0 / 36	2 / 35

Outcome results

Primary

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.

Time frame: Baseline to post intervention - up to 6 weeks