Defined Green Tea Catechins in Treating Patients With Prostate Cancer Undergoing Surgery to Remove the Prostate

Study Overview
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Brief Summary
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Green tea extract contains ingredients that may prevent or slow the growth of prostate cancer. This phase I trial is studying how well green tea extract works in treating patients with prostate cancer undergoing surgery to remove the prostate

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the bioavailability of defined green tea catechin extract in prostate tissue after treatment with defined green tea extract in patients with prostate cancer. SECONDARY OBJECTIVES: I. Determine the effect of this treatment on changes in clusterin levels and matrix metalloproteinase (MMP)-2 and MMP-9 in prostate tissue from these patients. II. Determine the effect of this treatment on changes in serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 in these patients. III. Determine the effect of this treatment on changes in oxidative DNA damage in peripheral blood leukocytes in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral defined green tea catechin extract daily for 4-7 weeks. Arm II: Patients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent. Biopsies are taken at the time of surgery. Plasma and tissue catechin levels are measured with high performance liquid chromatography (HPLC). 8OHdG levels in peripheral blood are measured with HPLC and mass spectometry. Immunohistochemistry is used to measure matrix metalloproteinase (MMP)-2, MMP-9, and clusterin. Insulin-like growth factor (IGF)-1 and IGF binding protein-3 are measured with immunoenzyme techniques.

Official Title
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Phase Ib Study of Polyphenon E in a Pre-prostatectomy Prostate Cancer Cohort

Conditions
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Adenocarcinoma of the Prostate, Stage I Prostate Cancer, Stage II Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: defined green tea catechin extract
* Drug: placebo
* Other: immunohistochemistry staining method
* Other: immunoenzyme technique
* Other: laboratory biomarker analysis
* Procedure: biopsy
* Other: mass spectrometry
* Other: high performance liquid chromatography


Participation Criteria
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Eligibility Criteria
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Criteria: Biopsy-proven adenocarcinoma of the prostate meeting the following criteria: organ-confined disease; treatable by prostatectomy PSA < 50 ng/mL ECOG performance status (PS) 0-1 or Karnofsky PS 70-100% Bilirubin normal AST and ALT normal Creatinine normal Fertile patients must use effective contraception No uncontrolled intercurrent illness including, but not limited to, any of the following: ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; psychiatric illness or social situations that would limit study compliance No history of allergic reactions attributed to compounds of similar chemical or biologic composition to green tea extract No prior therapy for prostate cancer (i.e., hormone therapy, radiation therapy, or surgery) No systemic treatment (chemotherapy) and/or radiation therapy for any malignancy within the past 5 years (excluding nonmelanoma skin cancer or cancer confined to organs with surgical removal as the only treatment) No regular tea consumption (> 6 servings of hot tea or 12 servings of iced tea or equivalent combination per week) within the past month No other concurrent investigational agents No other concurrent consumption of tea or tea-derived products from green, black, or oolong tea

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (green tea catechin extract)<br>Patients receive oral defined green tea catechin extract daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent. | Dietary Supplement: defined green tea catechin extract<br>* Given orally<br>* Other names: Polyphenon E;Other: immunohistochemistry staining method<br>* Correlative studies<br>* Other names: immunohistochemistry;Other: immunoenzyme technique<br>* Correlative studies<br>* Other names: immunoenzyme techniques;Other: laboratory biomarker analysis<br>* Correlative studies<br>Procedure: biopsy<br>* Undergo biopsy<br>* Other names: biopsies;Other: mass spectrometry<br>* Correlative studies<br>Other: high performance liquid chromatography<br>* Correlative studies<br>* Other names: HPLC;|
| Placebo Comparator: Arm II (placebo)<br>Patients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent. | Drug: placebo<br>* Given orally<br>* Other names: PLCB;Other: immunohistochemistry staining method<br>* Correlative studies<br>* Other names: immunohistochemistry;Other: immunoenzyme technique<br>* Correlative studies<br>* Other names: immunoenzyme techniques;Other: laboratory biomarker analysis<br>* Correlative studies<br>Procedure: biopsy<br>* Undergo biopsy<br>* Other names: biopsies;Other: mass spectrometry<br>* Correlative studies<br>Other: high performance liquid chromatography<br>* Correlative studies<br>* Other names: HPLC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-treatment green tea catechin concentration levels in prostate tissue | Descriptive statistics will be performed on prostate tissue EGCG within each intervention group. The difference in concentration levels between the two intervention groups will be tested using a two-group t-test at a one-sided 0.05 level of significance. If the distributions are not symmetrical, a non-parametric Wilcoxon test will be considered. The percentage of patients positive for EGCG in prostate tissue will be compared between the intervention groups using a Fisher's exact test of proportions at a one-sided 0.05 level of significance. | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in clusterin, matrix metalloproteinase (MMP)-2, and MMP-9 levels | Will be compared between intervention groups using a two-group t-test with a 0.05 two-sided significance level; with a sample size of 23 patients per group, there will be over 90% power to detect a difference equal to an effect size of 1.0. If the distributions are not symmetrical, a non-parametric Wilcoxon test will be considered. Correlations among the various biomarkers, as well as between post-intervention EGCG concentrations and changes in biomarker levels, will be explored (using Pearson or Spearman Rank correlation coefficients as appropriate). | Baseline to post-treatment | 
| Changes in Serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein-3 | Will be compared between intervention groups using a two-group t-test with a 0.05 two-sided significance level; with a sample size of 23 patients per group, there will be over 90% power to detect a difference equal to an effect size of 1.0. If the distributions are not symmetrical, a non-parametric Wilcoxon test will be considered. Correlations among the various biomarkers, as well as between post-intervention EGCG concentrations and changes in biomarker levels, will be explored (using Pearson or Spearman Rank correlation coefficients as appropriate). | Baseline to post-treatment | 
| Change in ratio of 8OHdG:dG | Statistical analysis will focus on the change scores (defined as changes from baseline to post-intervention). Changes in the Polyphenon E group will be compared with those in the placebo group, using a two-sided t-test. | Baseline to post-treatment | 
| Change in plasma levels of EGCG | Will be compared between groups, and the correlation of plasma and prostate tissue levels will be examined; however, plasma levels are expected to be low because of the washout during pre-operative fasting. Additional exploratory analyses will investigate the correlation of EGCG tissue levels with adherence during the intervention period (assessed primarily by capsule counts). | Baseline to post-treatment |