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

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.