Trial Outcomes & Findings for Phase II Clinical Trial of Purified Isoflavones in Prostate Cancer: Comparing Safety, Effectiveness (NCT NCT01036321)
NCT ID: NCT01036321
Last Updated: 2019-08-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
71 participants
Primary outcome timeframe
Baseline to post intervention - up to 6 weeks
Results posted on
2019-08-06
Participant Flow
Participants were enrolled from January 2010 through May 2014 at three sites in Florida.
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.
Participant milestones
| Measure |
Active Comparator: Purified Isoflavones
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Overall Study
STARTED
|
36
|
35
|
|
Overall Study
COMPLETED
|
31
|
31
|
|
Overall Study
NOT COMPLETED
|
5
|
4
|
Reasons for withdrawal
| Measure |
Active Comparator: Purified Isoflavones
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Overall Study
Ineligible after randomization
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Adverse Event
|
2
|
1
|
Baseline Characteristics
Phase II Clinical Trial of Purified Isoflavones in Prostate Cancer: Comparing Safety, Effectiveness
Baseline characteristics by cohort
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
Total
n=71 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.8 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
59.1 years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
58.9 years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
36 participants
n=5 Participants
|
35 participants
n=7 Participants
|
71 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to post intervention - up to 6 weeksPopulation: All participants who were randomized to a study arm.
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.
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Median Change in Percent Ki-67 From Baseline
All Participants
|
0.5 percentage of tumor cells
Interval 0.0 to 2.0
|
1.0 percentage of tumor cells
Interval 0.0 to 6.0
|
|
Median Change in Percent Ki-67 From Baseline
Caucasian Men (CM)
|
1.0 percentage of tumor cells
Interval 0.0 to 2.0
|
1.0 percentage of tumor cells
Interval 0.0 to 6.0
|
|
Median Change in Percent Ki-67 From Baseline
African American Men (AAM)
|
0.3 percentage of tumor cells
Interval 0.0 to 0.5
|
1.0 percentage of tumor cells
Interval 1.0 to 1.0
|
PRIMARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study 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.
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Number of Toxicity Events by Final Attribution and Treatment Arm
Possibly related
|
37 Toxicity Events
|
37 Toxicity Events
|
|
Number of Toxicity Events by Final Attribution and Treatment Arm
Probably related
|
4 Toxicity Events
|
0 Toxicity Events
|
|
Number of Toxicity Events by Final Attribution and Treatment Arm
Relation unlikely
|
17 Toxicity Events
|
9 Toxicity Events
|
|
Number of Toxicity Events by Final Attribution and Treatment Arm
Unrelated
|
24 Toxicity Events
|
20 Toxicity Events
|
|
Number of Toxicity Events by Final Attribution and Treatment Arm
Total
|
82 Toxicity Events
|
66 Toxicity Events
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
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).
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Biomarkers of Disease Progression - Serum PSA
ALL
|
-0.7 ng/mL
Interval -3.5 to 1.2
|
-0.2 ng/mL
Interval -3.2 to 2.7
|
|
Biomarkers of Disease Progression - Serum PSA
CM only
|
-0.8 ng/mL
Interval -3.5 to 1.2
|
-0.2 ng/mL
Interval -2.9 to 2.7
|
|
Biomarkers of Disease Progression - Serum PSA
AAM only
|
-0.3 ng/mL
Interval -2.5 to 1.2
|
-1.0 ng/mL
Interval -3.2 to 2.0
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
Plasma concentrations of isoflavone: Genistein from baseline to post intervention by study arm.
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Change in Plasma Concentrations of Isoflavone
|
0.00 mg
Interval -3.06 to 0.37
|
-0.02 mg
Interval -1.36 to 0.47
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Biomarkers of Disease Progression - Estradiol
Pre: Estradiol pmo/L
|
37.5 pmo/L
Interval 18.0 to 67.0
|
37.0 pmo/L
Interval 17.0 to 67.0
|
|
Biomarkers of Disease Progression - Estradiol
Post:
|
39.0 pmo/L
Interval 15.0 to 71.0
|
39.5 pmo/L
Interval 17.0 to 60.0
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Biomarkers of Disease Progression - Free Testosterone
Pre: Free testosterone (pg/ml)
|
59.9 pg/ml
Interval 21.3 to 101.0
|
49.1 pg/ml
Interval 30.4 to 134.0
|
|
Biomarkers of Disease Progression - Free Testosterone
Post:
|
54.8 pg/ml
Interval 17.6 to 119.0
|
62.9 pg/ml
Interval 24.8 to 106.0
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Biomarkers of Disease Progression - Insulin Like Growth Factor (IGF) Binding Protein -3
Pre: IGF Binding Protein -3 (mg/L)
|
3.9 mg/L
Interval 1.8 to 5.5
|
4.3 mg/L
Interval 1.7 to 6.4
|
|
Biomarkers of Disease Progression - Insulin Like Growth Factor (IGF) Binding Protein -3
Post:
|
3.8 mg/L
Interval 1.7 to 4.7
|
4.2 mg/L
Interval 2.0 to 5.6
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Biomarkers of Disease Progression - IGF-1
Pre: IGF-1 (ng/mL)
|
160.0 ng/mL
Interval 0.0 to 288.0
|
143.0 ng/mL
Interval 52.0 to 285.0
|
|
Biomarkers of Disease Progression - IGF-1
Post:
|
153.0 ng/mL
Interval 53.0 to 258.0
|
143 ng/mL
Interval 71.0 to 301.0
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Biomarkers of Disease Progression - Sex Hormone-binding Globulin (SHBG)
Pre: SHBG nmol/L
|
34.0 nmol/L
Interval 14.0 to 92.0
|
32.0 nmol/L
Interval 12.0 to 110.0
|
|
Biomarkers of Disease Progression - Sex Hormone-binding Globulin (SHBG)
Post:
|
35.0 nmol/L
Interval 13.0 to 61.0
|
32.0 nmol/L
Interval 14.0 to 81.0
|
SECONDARY outcome
Timeframe: Up to 6 weeksPopulation: All participants who were randomized to a study arm.
Median change from baseline to post intervention. Steroid hormones: pre-treatment (Pre:) versus post treatment (Post:).
Outcome measures
| Measure |
Active Comparator: Purified Isoflavones
n=36 Participants
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 Participants
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Biomarkers of Disease Progression - Total Testosterone
Pre: Total Testosterone (ng/dL)
|
358.0 ng/dL
Interval 93.0 to 738.0
|
348.0 ng/dL
Interval 179.0 to 979.0
|
|
Biomarkers of Disease Progression - Total Testosterone
Post:
|
376.0 ng/dL
Interval 163.0 to 709.0
|
295.0 ng/dL
Interval 196.0 to 1157.0
|
Adverse Events
Active Comparator: Purified Isoflavones
Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths
Placebo Comparator: Methyl Cellulose Blend
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Active Comparator: Purified Isoflavones
n=36 participants at risk
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 participants at risk
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • Number of events 1 • 4 years, 6 months
|
|
Injury, poisoning and procedural complications
Inoperative hemorrhage
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • Number of events 1 • 4 years, 6 months
|
Other adverse events
| Measure |
Active Comparator: Purified Isoflavones
n=36 participants at risk
Soy-based isoflavone concentrate with methyl cellulose blend filler - 2 capsules daily.
|
Placebo Comparator: Methyl Cellulose Blend
n=35 participants at risk
Placebo: Methyl cellulose blend - 2 capsules daily.
|
|---|---|---|
|
Gastrointestinal disorders
Stomach cramps
|
0.00%
0/36 • 4 years, 6 months
|
5.7%
2/35 • 4 years, 6 months
|
|
Investigations
Aspartate aminotransferase increased
|
8.3%
3/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Investigations
Blood bilirubin increased
|
5.6%
2/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Constipation
|
2.8%
1/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
5.6%
2/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Occasional Diarrhea
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Belching
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, GI symptoms
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.8%
1/36 • 4 years, 6 months
|
11.4%
4/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
2.8%
1/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Investigations
Investigations - Other, Elevated total testosterone
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Investigations
Investigations - Other, Low hemoglobin
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Investigations
Investigations - Other, Low RBC
|
0.00%
0/36 • 4 years, 6 months
|
5.7%
2/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, Low carbon dioxide
|
13.9%
5/36 • 4 years, 6 months
|
11.4%
4/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, Low globulin
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, Low protein
|
2.8%
1/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Nausea
|
2.8%
1/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.8%
1/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, Urination discomfort
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Sinus infection
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Gastrointestinal disorder - Other, Tender stomach
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/36 • 4 years, 6 months
|
2.9%
1/35 • 4 years, 6 months
|
|
General disorders
Fatigue
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Flatulence
|
8.3%
3/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Gastrointestinal disorder - Other, Darkening of stool
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Soft stool
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
General disorders
General disorders - Other, Feeling of fullness
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Investigations
Investigations - Other, Elevated estradiol
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Investigations
Investigations - Other, Low serum Co2
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Investigations
Investigations - Other, Low total testosterone
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, Elevated albumin
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, Low creatinine
|
5.6%
2/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, Slow stream
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Gastrointestinal disorders
Stomach pain
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Renal and urinary disorders
Renal and urinary disorders, Other - Frequent urination
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Renal and urinary disorders
Renal and urinary disorders, Other - Frequent urination (night)
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
|
Investigations
White blood cell decreased
|
2.8%
1/36 • 4 years, 6 months
|
0.00%
0/35 • 4 years, 6 months
|
Additional Information
Nagi Kumar, Ph.D.
H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-6885
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place