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

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

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

Study Overview

• Status: Completed
• Conditions: Stage I Prostate Cancer; Stage II Prostate Cancer; Adenocarcinoma of the Prostate
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Other: mass spectrometry; Drug: placebo; Procedure: biopsy; Dietary supplement: defined green tea catechin extract; Other: immunoenzyme technique; Other: high performance liquid chromatography

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center - Tucson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Frederick Ahmann, Arizona Cancer Center - Tucson

Publications and helpful links

General Publications

• Nguyen MM, Ahmann FR, Nagle RB, Hsu CH, Tangrea JA, Parnes HL, Sokoloff MH, Gretzer MB, Chow HH. Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities. Cancer Prev Res (Phila). 2012 Feb;5(2):290-8. doi: 10.1158/1940-6207.CAPR-11-0306. Epub 2011 Nov 1.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: April 9, 2007
• First Submitted That Met QC Criteria: April 9, 2007
• First Posted (ESTIMATE): April 11, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): October 8, 2014
• Last Update Submitted That Met QC Criteria: October 7, 2014
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Epigallocatechin gallate
• Other Study ID Numbers: NCI-2009-00894; N01CN35158 (U.S. NIH Grant/Contract); HSC # 06-0695-04; CDR0000538554 (REGISTRY: PDQ (Physician Data Query))