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

Phase 1
Completed
Conditions
Adenocarcinoma of the Prostate
Stage II Prostate Cancer
Stage I Prostate Cancer
Interventions
Drug: placebo
Dietary Supplement: defined green tea catechin extract
Other: immunohistochemistry staining method
Other: immunoenzyme technique
Other: laboratory biomarker analysis
Procedure: biopsy
Other: mass spectrometry
Other: high performance liquid chromatography
Registration Number
NCT00459407
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
50
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I (green tea catechin extract)laboratory biomarker analysisPatients 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.
Arm I (green tea catechin extract)high performance liquid chromatographyPatients 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.
Arm II (placebo)placeboPatients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent.
Arm II (placebo)immunohistochemistry staining methodPatients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent.
Arm II (placebo)immunoenzyme techniquePatients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent.
Arm II (placebo)mass spectrometryPatients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent.
Arm II (placebo)high performance liquid chromatographyPatients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent.
Arm I (green tea catechin extract)defined green tea catechin extractPatients 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.
Arm I (green tea catechin extract)immunohistochemistry staining methodPatients 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.
Arm II (placebo)biopsyPatients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent.
Arm I (green tea catechin extract)immunoenzyme techniquePatients 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.
Arm I (green tea catechin extract)biopsyPatients 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.
Arm I (green tea catechin extract)mass spectrometryPatients 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.
Arm II (placebo)laboratory biomarker analysisPatients receive oral placebo daily for 4-7 weeks. All patients undergo surgery one day after the last dose of study agent.
Primary Outcome Measures
NameTimeMethod
Post-treatment green tea catechin concentration levels in prostate tissueUp to 6 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Change in ratio of 8OHdG:dGBaseline to post-treatment

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.

Changes in clusterin, matrix metalloproteinase (MMP)-2, and MMP-9 levelsBaseline to post-treatment

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).

Changes in Serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein-3Baseline to post-treatment

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).

Change in plasma levels of EGCGBaseline to post-treatment

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).

Trial Locations

Locations (1)

Arizona Cancer Center - Tucson

🇺🇸

Tucson, Arizona, United States

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