Defined Green Tea Catechin Extract in Treating Patients With Localized Prostate Cancer Undergoing Surgery

Phase II, Randomized, Double Blind, Placebo Controlled Pilot Study of Polyphenon E in Men With Localized Prostate Cancer Scheduled to Undergo Radical Prostatectomy

This randomized pilot phase II trial studies the side effects and how well defined green tea catechin extract works in treating patients with localized prostate cancer undergoing surgery. Defined green tea catechin extract contains ingredients that may prevent or slow the growth of certain cancers.

OBJECTIVES:

I. To evaluate the short-term effects of daily Polyphenon E (defined green tea catechin extract) administration (800 mg epigallocatechin-3-gallate [EGCG] once daily [QD]) during the interval between prostate biopsy and radical prostatectomy (approximately 6 weeks) in men with localized prostate cancer.

II. Compare the change in levels of intermediate biomarkers (Ki-67, B-cell lymphoma 2 [Bcl2], cyclin D, KiP1/P27, vascular endothelial growth factor [VEGF], and cluster of differentiation [CD]31) in biopsy (pre-treatment) and prostatectomy (post-treatment) specimens collected from subjects treated with Polyphenon E or placebo during the period between biopsy and prostatectomy.

III. Compare the change in pre- and post-treatment serum prostate-specific antigen (PSA) level in subjects treated with Polyphenon E or placebo during the period between biopsy and prostatectomy.

IV. Evaluate bioavailability of catechins from Polyphenon E (plasma and tissue catechin levels, catechin metabolites in urine).

V. Evaluate the safety and tolerability of Polyphenon E in this subject population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive defined green tea catechin extract orally (PO) QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.

ARM II: Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

• Prostate biopsy positive for cancer; clinically localized T1 and T2 stage disease expected, with biopsy specimen available for baseline biomarker measurements
• Scheduled for a radical prostatectomy
• Willing to sign an Institutional Review Board (IRB)-approved informed consent document and adhere to the protocol
• Willing and able to take oral medications
• Willing to refrain from drinking any kind of tea (including herbal tea) or using supplements containing green tea constituents for the duration of the study

Exclusion Criteria:

• Prior hormonal or surgical therapy for prostate cancer; including prior brachytherapy or radiation therapy
• Recent consumption of tea (six or more cups per day) or use of supplements containing green tea within one week of randomization
• Signs or symptoms of progressive or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease
• Serum creatinine >= 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) >= ULN
• Aspartate aminotransferase (AST) >= ULN
• Alkaline phosphatase (ALP) >= ULN
• Albumin (ALB) =< lower limit of normal (LLN)
• Total bilirubin >= ULN
• Known malignancy at any site within the last five years; with the exception of basal cell carcinoma (BCC)
• Participation in a research trial within the past three months
• Any condition that would interfere with the ability to give informed consent or comply with the study protocol
• Hypersensitivity to tea products or any of the inactive ingredients found in the drug product capsules
• Concomitant use of at least 400 mg per day of a nonsteroidal anti-inflammatory (NSAID) agent two or more times per week