Clinical Trial of Green Tea Catechins in Men on Active Surveillance

Study Overview
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Brief Summary
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This randomized double-blinded Phase II clinical trial will evaluate the bioavailability, safety, effectiveness and validate the mechanism by which a standardized formulation of whole Green Tea Catechin, (Sunphenon® 90D) containing 405 mgs vs. Placebo, administered for 24 months in a cohort of men with low to intermediate grade prostate managed on active surveillance

Official Title
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Phase II Clinical Trial of Green Tea Catechins in Men on Active Surveillance (AS)

Conditions
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Prostate Cancer, Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: Sunphenon
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Biopsy-proven (consisting of ≥ 12 tissue cores) adenocarcinoma of the prostate with cancer present in at least one biopsy core (TRUS or/and mpMRI/TRUS fusion), Gleason score (3+3) or predominant Gleason pattern 3 (3+4), ≤ 33% of biopsy cores, and ≤50% involvement of any biopsy core (Participant meets all criteria for Active Surveillance as determined by MD) Willing to start or continue on active surveillance Baseline/screening serum PSA <10 ng/mL No other prior treatment for PCa, including focal therapy ECOG performance status 0-1 No history of renal or hepatic disease, including history of hepatitis B and C Meet hematological eligibility parameters (Neutrophil count ≥ 1,200/mm3 (≥1.2 k/μL), Stable platelet count ≥ 75,000/mm3 (≥ 75k/μL) Hepatic and renal function eligibility parameters, serum total Bilirubin ≤ULN (ULN: 1.2 mg/dl) (or ≤3.0 mg/dL for patients with Gilbert's syndrome), AST or ALT <1.5x ULN and Serum creatinine ≤1.5 x ULN Willing to abstain from consumption of any supplements containing GTC Willing to restrict tea consumption to less than three (3) servings of hot tea or three (3) servings of iced tea per week Willing to discontinue current vitamin/mineral supplement use and use one provided by study Willing to take study agent or placebo at the dose specified with meals. Exclusion Criteria: Have had prior treatment for PCa by surgery, irradiation, local ablative (i.e., cryosurgery or high-intensity focused ultrasound), or androgen-deprivation therapy) Men who are currently treated or those treated in the past 3 months prior to day of randomization with 5- alpha-reductase inhibitors (e.g., finasteride, dutasteride) Participants who have PCa with distant metastases Participants who have been treated with: hormone therapy, immunotherapy, chemotherapy and/or radiation, for any malignancies within the past 2 years prior to 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. All patients with metastatic disease will be excluded Participants may not be receiving any other investigational agents History of allergic reactions attributed to tea or compounds of similar chemical or biologic composition to green tea extracts.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants participating in the study will be randomized 2:1 (2 study agent: 1 placebo) to receive Sunphenon® 90D (405 mg EGCG BID) or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunphenon® 90D<br>Participants will be administered a standardized formulation of whole Green Tea Catechin for 24 months. The daily dose of Green Tea Catechin will be taken in divided doses, three capsules in the morning and 3 capsules in the evening, with food (within one hour of eating a substantial meal). On the day of monthly follow-up visit, capsules should be taken within 4 hours of visit and blood draw for required lab work. If the participant is scheduled to come in the afternoon, dose should be taken with lunch that day instead of with dinner for that day. | Drug: Sunphenon<br>* The study agent will be administered in divided doses with food, three capsules twice a day (405 mg) for 24 months<br>* Other names: Green Tea Catechin;|
| Placebo Comparator: Placebo<br>Participants will be administered a placebo for 24 months. The daily dose of placebo will be taken in divided doses, three capsules in the morning and 3 capsules in the evening, with food (within one hour of eating a substantial meal). On the day of monthly follow-up visit, capsules should be taken within 4 hours of visit and blood draw for required lab work. If the participant is scheduled to come in the afternoon, dose should be taken with lunch that day instead of with dinner for that day. | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Progression to Prostate Cancer (PCa) | Number of participants with clinical progression defined as a composite outcome on repeat prostate biopsy >33% of biopsy cores positive for cancer or >50% of any biopsy tissue core positive for cancer or adverse reclassification of Gleason sum >3+3 or >3+4 respectively at end of study biopsy | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Adverse Events per Study Arm | Safety of Green Tea Catechins (GTC) at daily dose (vs. Placebo) as indicated by incidence of adverse events and toxicities, monitored using Common Toxicity Criteria version 5.0, complete blood count (CBC), and complete metabolic panel (CMP) from baseline, month 6, month 12 and month 24 at end of trial, Liver toxicities (LFTs) from baseline, month 3, 6 and every 3 months until end of intervention | Base line to 24 months | 
| Adherence of Green Tea Catechins vs.Placebo | Adherence based on pill counts and agent logs | Baseline to 24 months | 
| Acceptability of Green Tea Catechins vs.Placebo | Acceptability based on pill counts and agent logs | Baseline to 24 months | 
| Change in (prostate-specific antigen) PSA and PSA kinetics | PSA or PSA density and PSA doubling time at month 12 and at 24 months) from serum at baseline, 6, 12, 18 and month 24 | Baseline to 24 months | 
| Change in gene expression panel | Asses change in gene expression panel (Decipher) and a set of 13 biomarker genes known to be overexpressed in PCa from baseline to end of study (EOS) using biopsy tissue | Baseline to 24 months | 
| Proportion of men with no cancer | Assess the proportion of men with no cancer in the post-intervention biopsy | Baseline to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate, Green Tea, Green Tea Catechins