Study of Polyphenon E in Men With High-grade Prostatic Intraepithelial Neoplasia
The purpose of this study was to determine whether the daily consumption of decaffeinated green tea catechins (Polyphenon E®) for 1 year reduces the rate of progression to prostate cancer (PCa) in men diagnosed with HGPIN or ASAP. The aim was to recruit and treat 240 (120 men/arm) men diagnosed with the prostate condition HGPIN or ASAP with a capsule form of standardized green tea extract called Polyphenon E or placebo for a 12-month period and see if it can prevent progression of the prostate condition to prostate cancer. Investigators wanted to see if Polyphenon E reduces lower urinary tract symptoms and if this can be taken safely over one year. Investigators wanted to study how Polyphenon E is able to slow the progression to prostate cancer, or the mechanism of action of Polyphenon E. If the safety and the effects of Polyphenon E on slowing down the progression of prostate cancer is shown in our study, this will be a safe way of treating men who are at high risk or men like you who have a prostate condition that increases your chances of getting prostate cancer, so that we can prevent prostate cancer in the future.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Phase II, Randomized, Double-blind, Multi-centered Study of Polyphenon E in Men With High-grade Prostatic Intraepithelial Neoplasia (HGPIN) or Atypical Small Acinar Proliferation (ASAP)|
- Rate of Progression to Prostate Cancer (PCa) [ Time Frame: 12 months ] [ Designated as safety issue: No ]Number of participants with diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) who progressed to prostate cancer (PCa) at one year.
- Rate of Progression From HGPIN to ASAP or PCa [ Time Frame: 12 months ] [ Designated as safety issue: No ]Analyses of participants reaching a definitive endpoint. Number of baseline HGPIN participants who progressed to ASAP or PCa.
- Treatment Emergent Adverse Events (AEs) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Safety of Polyphenon E (200 mg EGCG bid for one year) in men with HGPIN or ASAP. Number of participants with AEs Possibly or Probably related to treatment.
- Occurrence of Grade 3 or Higher Adverse Events (AEs) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Number of participants with AEs grade 3 or higher, per treatment arm.
- Median Serum Total Prostatic Specific Antigen (tPSA) [ Time Frame: 12 months ] [ Designated as safety issue: No ]Median ng/mL serum tPSA post treatment, per treatment arm.
- Change in Scores - Lower Urinary Tract Symptom (LUTS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]Change in score from baseline to 1 year. LUTS represent a common conglomeration of storage, voiding, and post-micturition symptoms with reported debilitating effect on quality of life. Symptom severity related to urinary frequency, nocturia, weak urinary stream, hesitancy, intermittency, incomplete bladder emptying and urinary urgency are assessed. We utilized the American Urological Association Symptom Score for the evaluation LUTS in this patient population. Symptom Frequency Scores: 0 = Not at all, 1 = Less than 1 time in 5, 2 = Less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. Total Symptom Score = Sum of individual scores of the 7 symptoms. (minimum possible score=0; maximum possible score =35; Range of scores and significance: 0-7 mild symptoms; 8-19 moderate symptoms; 20-35 severe symptoms.
- Effect of Polyphenon E on the Fundamental Molecular Pathways [ Time Frame: 12 months ] [ Designated as safety issue: No ]Explore the effects of Polyphenon E on the fundamental molecular pathways contributing to chemopreventive activity of Polyphenon E in the prostate. This exploratory aim is ongoing.
|Study Start Date:||December 2007|
|Estimated Study Completion Date:||August 2016|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Polyphenon E Treatment
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Drug: Polyphenon E
Polyphenon E, at a dose of 400 mgs EGCG (200 mgs BID) for 1 year in men diagnosed with HGPIN and ASAP.
Placebo Comparator: Placebo Administration
Matching placebo BID
Matching placebo BID
At the baseline/randomization visit, a QOL (Medical Outcomes Study Short Form-36) and lower urinary tract symptoms (LUTS) score assessment will be completed; urine and serum will be collected for measurement of diagnostic markers; plasma will be collected for measurement of baseline catechin levels; serum will be collected for banking; and diet recall forms will be collected. Participants will be equally randomized to blinded treatment with either Polyphenon E 200 mg EGCG bid or matching placebo, and an initial supply of study drug will be dispensed. All participants will also be provided with a standard multivitamin/mineral supplement to assure consistent, appropriate nutrient intake among study participants. The planned intervention period is 12 months; participants will return for monthly clinic visits during the intervention period. At each monthly clinic visit, blood will be drawn for repeat hepatic function panel, lactate dehydrogenase (LDH) and prothrombin time/partial thromboplastin time (PT/PTT), and participants will be interviewed to review and capture information from study agent intake log (pill count), assess signs and symptoms and concomitant medications; additional study medication will be dispensed as needed. After 3 and 6 months of intervention, blood will be drawn for serum chemistry and hematology, and LUTS and QOL assessments will be performed. In addition, at the 6 month visit, two-day diet recall forms will be collected, blood will be drawn for plasma catechin measurements and serum banking, serum and urine will be collected for diagnostic marker measurement, and repeat digital rectal exam (DRE) and prostate specific antigen (PSA) will be performed. If there is a palpable prostate nodule or confirmed PSA increase (>0.75 ng/ml) at 6 months, a repeat biopsy will be performed. If the 6-month biopsy shows evidence of disease progression, participants will stop intervention and proceed to the post-intervention assessment; otherwise, intervention will continue through month 12. At the end of intervention (maximum of 12 months), a repeat prostate biopsy will be performed for post-intervention endpoint measurements. In addition, the physical exam and DRE, LUTS and QOL will be repeated, and 2-day diet recall forms will be collected. Blood will be drawn for serum chemistry and hematology, PSA, hepatic function panel, LDH, PT/PTT; serum and urine will be collected for diagnostic marker measurement; plasma will be collected for catechin measurements; and serum will be collected for banking. Participants will be interviewed to review and capture information from study agent intake log (pill count), assess signs and symptoms and concomitant medications.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00596011
|United States, Florida|
|University of Florida/Shands-Department of Urology|
|Gainesville, Florida, United States, 32610|
|University of Florida - Jacksonville|
|Jacksonville, Florida, United States, 32209|
|Watson Clinic Center for Research, Inc.|
|Lakeland, Florida, United States, 33805|
|H Lee Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|James A Haley VA|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|University of Chicago - Department of Surgery|
|Chicago, Illinois, United States, 60637|
|United States, Louisiana|
|LSU Health Sciences Center, Feist-Weiller Cancer Center|
|Shreveport, Louisiana, United States, 71130|
|Overton Brooks VA Medical Center|
|Shreveport, Louisiana, United States, 71101-4295|
|United States, Minnesota|
|Minneapolis VA Medical Center|
|Minneapolis, Minnesota, United States, 55417|
|United States, Pennsylvania|
|Jefferson Medical College - Department of Urology|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Nagi Kumar, PhD||H. Lee Moffitt Cancer Center|