Clinical Trial: Study of Polyphenon E in Men With High-grade Prostatic Intraepithelial Neoplasia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Prolif

Brief Summary: 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.

Detailed Summary: 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
Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Current Primary Outcome:

  • Rate of Progression to Prostate Cancer (PCa) [ Time Frame: 12 months ]
    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 ]
    Analyses of participants reaching a definitive endpoint. Number of baseline HGPIN participants who progressed to ASAP or PCa.


Original Primary Outcome:

  • rate of progression to prostate cancer at one year in men treated with Polyphenon E (200 mg EGCG bid) following diagnosis of HGPIN. [ Time Frame: 12 months ]
  • safety of Polyphenon E (200 mg EGCG bid for one year) in men with HGPIN [ Time Frame: 12 months ]
  • the effect of Polyphenon E treatment on quality of life in men diagnosed with HGPIN. Evaluate the effect of Polyphenon E treatment on LUTS and QOL in men diagnosed with HGPIN. [ Time Frame: 12 months ]


Current Secondary Outcome:

  • Treatment Emergent Adverse Events (AEs) [ Time Frame: 12 months ]
    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 ]
    Number of participants with AEs grade 3 or higher, per treatment arm.
  • Median Serum Total Prostatic Specific Antigen (tPSA) [ Time Frame: 12 months ]
    Median ng/mL serum tPSA post treatment, per treatment arm.


Original Secondary Outcome:

  • the effect of Polyphenon E treatment on levels of ABCA5 in urine and PCADM-1 in serum [ Time Frame: 6 and 12 months ]
  • Explore the effects of Polyphenon E on the fundamental molecular pathways contributing to chemopreventive activity of Polyphenon E in the prostate [ Time Frame: 12 months ]


Information By: H. Lee Moffitt Cancer Center and Research Institute

Dates:
Date Received: January 7, 2008
Date Started: November 14, 2007
Date Completion: December 2017
Last Updated: April 18, 2017
Last Verified: April 2017