Study of Polyphenon E in Men With High-grade Prostatic Intraepithelial Neoplasia
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.
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.
Inclusion Criteria:

 -  Men with a diagnosis of HGPIN or ASAP in a minimum of 1 of 8 cores from a biopsy
 performed within six months of study entry. Diagnosis of HGPIN or ASAP (which includes
 men with ASAP and HGPIN) via trans-rectal ultrasound (TRUS biopsy) is also considered
 acceptable for inclusion.

 -  Prostate biopsy with a minimum of 8 cores performed within 6 months of study entry
 that shows no evidence of cancer.

 -  30-80 years of age at the time of registration

 -  PSA ≤10 ng/ml

 -  Omnivorous diet

 -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

 -  Participants must have normal organ and marrow function as demonstrated by the
 following parameters being within normal institutional limits: complete blood count
 (CBC); liver function tests (LFTs); albumin, total and direct bilirubin, alkaline
 phosphatase, aspartic transaminase (AST), alanine transaminase (ALT), and total
 protein), PT/PTT, and LDH; serum creatinine <1.5 mg/dl or measured creatinine
 clearance 60 cc/min

 -  Absence of consumption of toremifene citrate, finasteride, testosterone,
 dehydroepiandrosterone (DHEA) or other testosterone-like supplements or medications
 which have known impact on PSA within 30 days of informed consent, or dutasteride
 within 90 days of informed consent

 -  Absence of consumption of any nutritional or herbal supplements containing green tea
 or green tea polyphenols

 -  No or low regular tea consumption (no more than 3 servings of hot tea or 6 servings of
 iced tea per week)

 -  Willing to discontinue current vitamin/mineral supplement use and substitute with a
 standard multivitamin supplement provided for the study

 -  Willing to use an effective method of contraception, if the partner is of
 child-bearing age, while on study

 -  Willing to comply with proposed visit and treatment schedule

 -  Able to understand and willing to sign a written informed consent document

 Exclusion Criteria:

 -  Evidence of acute prostatitis or urinary tract infection at the time of PSA
 measurement; men may be enrolled 30 days after completion of treatment, provided all
 other eligibility criteria are met

 -  Current or prior history of prostate cancer or other malignancies (exceptions include
 non-melanoma skin cancer or other cancer with no evidence of tumor recurrence 5 years
 after definitive treatment)

 -  History of renal or hepatic disease, including history of hepatitis B, C or delta

 -  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 tea or other compounds of similar chemical
 or biologic composition to Polyphenon E or the inactive components present in
 Polyphenon E 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

 -  History of medical conditions that may predispose the participant to gastrointestinal
 bleeding (acute or chronic gastritis or colitis, or acute diverticulitis or
 hemorrhoids)

 -  Members of all races and ethnic groups are eligible for this trial. Since this is an
 investigation targeting men with HGPIN or ASAP, women are not eligible for the study.