To Evaluate if Green Tea Can be Effective in Reducing the Progression of Prostate Cancer in Men on Close Monitoring

Study Overview
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Brief Summary
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This phase II trial studies how well green tea catechins work in preventing progression of prostate cancer from a low risk stage to higher risk stages in men who are on active surveillance. Green tea catechins may stabilize prostate cancer and lower the chance of prostate growing.

Detailed Description
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PRIMARY OBJECTIVE: I. To compare the change in the percent (%) Ki-67 expression in a biopsy core positive for cancer from baseline to end-of-study (EOS) biopsy between men on active surveillance (AS) for prostate cancer (PCa), treated with green tea catechins (GTCs) or placebo for 6 months. SECONDARY OBJECTIVES: I. To assess apoptosis by caspase in tumor tissue from EOS biopsy by treatment. II. To assess % Ki-67: Apoptosis ratio from EOS biopsy by treatment. III. To evaluate the number of biopsy cores positive for cancer from EOS biopsy by treatment. IV. To evaluate the percentage of any biopsy tissue core positive for cancer from EOS biopsy by treatment. V. To evaluate % Ki-67 in EOS biopsy from the same quadrant matching the quadrant with the highest % Ki-67 at baseline treatment. VI. To evaluate the Gleason sum from EOS biopsy by treatment. VII. To evaluate the change in serum prostate-specific antigen (PSA) from baseline to 3 months and to EOS by treatment. VIII. To evaluate the safety of 6 month administration of GTC assessed by Common Toxicity Criteria (CTC) version 5.0, complete blood count (CBC), comprehensive metabolic panel (CMP) and liver function toxicities (LFTs) by treatment. IX. To evaluate the change in geometric mean of % Ki-67 measures in all the cores positive for cancer from baseline to EOS biopsy by treatment. EXPLORATORY OBJECTIVES: I. To evaluate the change in catechin (epigallocatechin gallate [EGCG]) as indicated by change from EGCG measured in plasma from baseline and EOS by treatment. II. To evaluate the adherence and acceptability to GTC based on the percentage compliance using agent logs (%) and pill counts monthly until EOS by treatment groups. III. To evaluate the bioavailability of GTC as indicated by change from EGCG measured in plasma from baseline and EOS by treatment groups. PATIENT REPORTED OUTCOMES OBJECTIVES: I. To evaluate the change in lower urinary tract symptoms (LUTS) from baseline to 3 months and to EOS using the LUTS scale by treatment groups. II. To evaluate the change in quality of life (QOL) scores from baseline to 3 months and to EOS using the Functional Assessment of Cancer Therapy (FACT)-Prostate by treatment groups. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive green tea catechins orally (PO) twice daily (BID) for up to 6 months in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive placebo PO BID for up to 6 months. After completion of study, patients are followed up at approximately 7 days, at 6 months, and then up to 12 months.

Official Title
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A Phase II Randomized Double Blinded Study of Green Tea Catechins (GTC) vs. Placebo in Men on Active Surveillance for Prostate Cancer: Modulation of Biological and Clinical Intermediate Biomarkers

Conditions
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Prostate Carcinoma

Intervention / Treatment
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* Drug: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Drug: Sinecatechins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: INCLUSION CRITERIA FOR PREREGISTRATION (STEP 0: SCREENING) Patient must have biopsy-proven (consisting of >= 12 tissue cores) adenocarcinoma of the prostate with cancer present in at least one biopsy core in the most recent biopsy using initial transrectal ultrasound (TRUS) biopsy or TRUS biopsy followed by multiparametric magnetic resonance imaging (mpMRI) of the prostate and a confirmatory targeted biopsy Patient must be on active surveillance (very low, low and favorable intermediate risk as defined by the National Comprehensive Cancer Network [NCCN]) Patient must be scheduled for a follow up prostate biopsy 6 months after the initiation of treatment on this study Patient must have a serum PSA < 10 ng/mL or prostate specific antigen density (PSAD) < 0.15 ng/mL/ g obtained within 30 days of registration Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Patient must be willing to abstain from consumption of any supplements containing green tea catechins Patient must be willing to restrict tea consumption to less than three (3) servings of hot tea or three (3) servings of iced tea per week (serving size of 8 oz) Patient must be willing to discontinue current vitamin/mineral supplement use and use one provided by study Patient must be willing to take study agent or placebo at the dose specified with meals Patient must have the ability to understand and the willingness to sign a written informed consent document Absolute neutrophil count >= 1,200/mm^3 (>= 1.2 k/uL) (obtained within 30 days prior to registration) Platelets >= 75,000/mm^3 (>= 75 k/uL) (obtained within 30 days prior to registration) Total bilirubin =< 1.2 mg/dL (or =< 3.0 mg/dL for patients with Gilbert's syndrome) (obtained within 30 days prior to registration) Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x upper limit of normal (ULN) (obtained within 30 days prior to registration) Serum creatinine =< 1.5 x ULN (obtained within 30 days prior to registration) Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial Sexually active males must use an accepted and effective method of double barrier contraception (vasectomy must be combined with a physical barrier method) or abstain from sexual intercourse for the duration of their participation in the study Patients must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen available for Gleason score confirmation and % Ki-67 expression (5% or more) in tumor tissue for eligibility and stratification. Tumor tissue can be submitted any time during screening Tumor tissue specimen has been collected and is ready to ship to H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt Cancer Center & Research Institute will perform Gleason score confirmation and % Ki-67 expression (5% or more) in tumor tissue and notify the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Operations Office and submitting institution within 3-4 business days of receipt of the tumor tissue specimen INCLUSION CRITERIA FOR RANDOMIZATION (STEP 1) Patient must meet all Step 0 eligibility criteria at the time of their registration to Step 1 Patient must have Gleason score (3+3) or predominant Gleason pattern 3 (3+4), =< 33% of biopsy cores, and =< 50% involvement of any biopsy core Patient must have % Ki-67 expression of 5% or more in tumor tissue Exclusion Criteria: EXCLUSION CRITERIA FOR PREREGISTRATION (STEP 0: SCREENING) Patient must not have had prior treatment for prostate cancer, including focal therapy, with surgery, irradiation, local ablative (i.e., cryosurgery or high-intensity focused ultrasound), or androgen deprivation therapy Patient must not have a history of renal or hepatic disease, including history of hepatitis B and C Patient must not have prostate cancer with distant metastases Patient must not have undergone treatment of hormone therapy, immunotherapy, chemotherapy and/or radiation for any malignancies within the past 2 years. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial Patient must not receive any other investigational agents while on this study Patient must not have a history of allergic reactions attributed to tea or other compounds of similar chemical or biologic composition to green tea extracts

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

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 A (green tea catechins)<br>Patients receive green tea catechins PO BID for up to 6 months in the absence of disease progression or unacceptable toxicity. | Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Sinecatechins<br>* Given PO<br>* Other names: Veregen;|
| Placebo Comparator: Arm B (placebo)<br>Patients receive placebo PO BID for up to 6 months. | Drug: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the highest percent Ki-67 expression | Measured in a core positive for tumor from baseline to highest percent (%) Ki-67 expression measured in a core positive for tumor in the end of study (EOS) biopsy. This change will be compared between green tea catechins (GTC) and placebo arms. The highest % Ki-67 expressions from baseline and EOS biopsies will be used to estimate the change. If the change is not normally distributed, non-parametric test such as Wilcoxon-rank sum test or two-sample normal score test will be used to compare the changes in percent Ki-67 levels between the GTC and placebo arms. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apoptosis | Will be assessed by caspase in tumor tissue from EOS biopsy by treatment. | Up to 6 months | 
| Apoptosis ratio | Will be evaluated from EOS biopsy by treatment groups. Descriptive statistics with confidence intervals will be presented. For continuous measures, will use two-sample t-test or Wilcoxon rank sum test (if non-parametric test is more appropriate) to compare the measurements by treatment. | Up to 6 months | 
| Number of biopsy cores positive for cancer at end of study | Descriptive statistics with confidence intervals will be presented. For binary measures, will use Fisher's test. | At 6 months | 
| Percent of any biopsy tissue core positive for cancer at end of study | Descriptive statistics with confidence intervals will be presented. For continuous measures, will use two-sample t-test or Wilcoxon rank sum test (if non-parametric test is more appropriate) to compare the measurements by treatment. | At 6 months | 
| Percent Ki-67 | Descriptive statistics with confidence intervals will be presented. For continuous measures, will use two-sample t-test or Wilcoxon rank sum test (if non-parametric test is more appropriate) to compare the measurements by treatment. | Up to 6 months | 
| Gleason sum at end of study | Descriptive statistics with confidence intervals will be presented. For binary measures, will use Fisher's test. | At 6 months | 
| Change in serum prostate-specific antigen (PSA) | Will use three mixed models (for PSA, PSA doubling time, and PSA density). For the first two, will log the PSA value. For PSA, will have intercepts and slopes for each patient, an unstructured covariance model, and 2 terms for the intercept and slope associated with the treatment group. For the PSA doubling time, will center the baseline values at 1, and estimate the slopes for each patient (from which the doubling time can be derived), along with a net slope effect for the treatment group. The mixed model for PSA density will be analogous to the one for PSA. | Baseline up to 6 months | 
| Incidence of adverse events | Will be assessed by Common Toxicity Criteria version 5.0, complete blood count, comprehensive metabolic panel, and liver function toxicities by treatment. All toxicity data will be summarized by category and grade in a standard fashion. Proportions experiencing the most common types of toxicity in this trial will be estimated and 95% confidence intervals calculated. Adverse event rates (such as worst grade 3 or higher) by arm will be estimated and compared. | Up to 12 months | 
| Change in geometric mean of percent Ki-67 | Descriptive statistics with confidence intervals will be presented. For binary measures, will use Fisher's test. | Baseline up to 6 months |