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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
360
Given PO
Ancillary studies
Ancillary studies
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.
Time frame: Baseline to 6 months
Apoptosis
Will be assessed by caspase in tumor tissue from EOS biopsy by treatment.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At 6 months
Percent Ki-67
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Given PO
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, United States
Mercy Hospital Fort Smith
Fort Smith, Arkansas, United States
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas, United States
CARTI Cancer Center
Little Rock, Arkansas, United States
Highlands Oncology Group - Rogers
Rogers, Arkansas, United States
Highlands Oncology Group
Springdale, Arkansas, United States
Mission Hope Medical Oncology - Arroyo Grande
Arroyo Grande, California, United States
Marshall Cancer Center
Cameron Park, California, United States
...and 343 more locations
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline up to 6 months