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
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
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.
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
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:
Brighton, Michigan 48114, United States
Chelsea, Michigan 48118, United States
East China, Michigan 48054, United States
Grosse Pointe Woods, Michigan 48236, United States
Macomb, Michigan 48044, United States
Warren, Michigan 48093, United States
West Branch, Michigan 48661, United States
Ypsilanti, Michigan 48197, United States