ELIGIBILITY CRITERIA FOR PREREGISTRATION (STEP 0: SCREENING)

Patient must be >= 21 years of age

Patient must speak English or Spanish

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 a TRUS biopsy or TP or an mpMRI-guided biopsy of the prostate

Patient must be on active surveillance (local - Gleason 3+3/Grade Group 1 [GG1] or Gleason 3+4/GG2) where < 6 of 12 cores are positive for cancer
* NOTE: In cases where the total number of biopsies are < 12 cores (6 or 8 cores), < 3/6 cores or < 4/8 cores must be positive for cancer to meet eligibility criteria

Patient’s baseline biopsy must have occurred at least 6 months but not more than 18 months prior to preregistration to step 0. 
* NOTE: Patient is to 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 obtained within 30 days of preregistration

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 if it contains green tea products 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. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

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 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 prior to step 0 pre-registration. 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

Patient should not be on Finasteride or Dutasteride during study
* NOTE: If patient is willing to discontinue these drugs and upon approval by patient’s Doctor of Medicine (MD), patient can proceed to be screened for this clinical trial

Patient must not have a history of other cancers except for nonmelanoma skin cancer

Absolute neutrophil count >= 1,200/mm^3 (>= 1.2 k/uL) (obtained within 30 days prior to step 0 pre-registration)

Platelets >= 75,000/mm^3 (>= 75 k/uL) (obtained within 30 days prior to step 0 pre-registration)

Total bilirubin =< 1.2 mg/dL (or =< 3.0 mg/dL for patients with Gilbert’s syndrome) (obtained within 30 days prior to step 0 pre-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 step 0 pre-registration)

Serum creatinine =< 1.5 x ULN (obtained within 30 days prior to step 0 pre-registration)

Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Patients must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen available for Gleason score confirmation (Gleason 3+3/GG1 or Gleason 3+4/GG2) and % Ki-67 expression (3% 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 in tumor tissue and notify the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Operations Office within 3-4 business days of receipt of the tumor tissue specimen

ELIGIBILITY CRITERIA FOR RANDOMIZATION (STEP 1)

Patient must meet all step 0 pre-registration eligibility criteria at the time of their step 1 randomization

Patient must be on active surveillance (Gleason 3+3/GG1 or Gleason 3+4/GG2) where < 6 of 12 cores are positive for cancer, confirmed via central review, as defined by the National Comprehensive Cancer
Network [NCCN])
* NOTE: In cases where the total number of biopsies are < 12 cores (6 or 8 cores), < 3/6 cores or < 4/8 cores must be positive for cancer to meet eligibility criteria and must be confirmed via central review

Patient must have % Ki-67 expression of 3% or more in at least 1 core positive for tumor confirmed via central review

Patient must not have a history of renal or hepatic disease, including history of hepatitis B (hepatitis B virus [HBV] core antibody) and C (hepatitis C virus [HCV] core antibody)

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 (GTC) 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 Terminology Criteria for Adverse Events (CTCAE), 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.

All patients also undergo transrectal ultrasound (TRUS), transperineal (TP), or multiparametric magnetic resonance imaging (mpMRI)-guided biopsies of the prostate during screening and on study. Patients also undergo collection of blood samples on study.

Patients are followed up at approximately 7 days and at 6 months after completion of study treatment and finally at 12 months after registration.