Study of Polyphenon E in Men With High-grade Prostatic Intraepithelial Neoplasia
The clinical study is a Phase II, randomized, double-blinded, placebo-controlled trial in men 30-80 years of age with biopsy proven HGPIN or atypical small acinar proliferation (ASAP) and no evidence of prostate cancer, prostatitis or urinary tract infection. A total of 272 men will be randomized to the study, with the goal of completing 240 evaluable participants. Participants who consent to the study and meet initial eligibility criteria will be undergo a one-week run-in period during which they will be asked to self-administer the supplement daily as well as complete study logs and two-day diet recall forms. Participants must meet all inclusion criteria and remain compliant during the run-in period to be randomized to a treatment arm. Participant will complete a quality of life (QOL) survey and have blood collected for baseline tests. Participants will be equally randomized (n=136 per arm) to blinded treatment with either Polyphenon E 200 mg epigallocatechin gallate (EGCG) twice a day (bid) or matching placebo. The planned intervention period is 12 months; participants will return for monthly clinic visits during the intervention period. After 3 and 6 months of intervention, blood will be drawn for serum chemistry and hematology, and other and lower urinary tract symptom (LUTS) and QOL assessments will be performed. In addition, at the 6 month visit, two-day diet recall forms will be collected, blood and urine will be collected, and repeat digital rectal exam (DRE) and prostatic 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. At the end of intervention (maximum of 12 months), a repeat prostate biopsy will be performed for post-intervention endpoint measurements. The primary endpoint of the study is a comparison of the incidence of prostate cancer between participants in the treatment vs. placebo arm; in addition, the prevalence of HGPIN or ASAP in pre-treatment and post-treatment biopsies in participants treated with Polyphenon E vs. placebo will be compared. If participants develop prostate cancer during the course of the study, the extent and grade of cancer will be assessed and compared between treatment groups.
|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 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Number of participants AEs grade 3, 4, or 5.
- 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.
- 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.
- Effect of Polyphenon E Treatment on Quality of Life (QOL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]Evaluate the effect of Polyphenon E treatment on lower urinary tract symptom (LUTS) and QOL in men diagnosed with HGPIN or ASAP. LUTS represent a common conglomeration of storage, voiding, and post-micturition symptoms with reported debilitating effect on quality of life.
|Study Start Date:||December 2007|
|Estimated Study Completion Date:||February 2015|
|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
Show Detailed Description
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|