Green Tea Catechins for the Prevention of Prostate Cancer Progression in Men on Active Surveillance
This phase II trial studies how well green tea catechins work for the prevention of disease progression in men with prostate cancer on active surveillance. Green tea catechins may help prevent progression of prostate cancer from a low risk stage to higher risk stages in men who are on active surveillance.
Inclusion Criteria
- Age >= 18 years of age
- Biopsy-proven (consisting of >= 12 tissue cores) adenocarcinoma of the prostate with cancer present in at least one biopsy core in biopsy (transrectal ultrasound [TRUS] or/and multiparametric magnetic resonance imaging [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 (patient meets all criteria for active surveillance as determined by Doctor of Medicine [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
- Eastern Cooperative Oncology Group (ECOG) performance status 0−1
- No history of renal or hepatic disease, including history of hepatitis B and C
- Neutrophil count >= 1,200/mm^3 (>= 1.2 k/uL)
- Stable platelet count >= 75,000/mm^3 (>= 75k/uL)
- Serum total bilirubin =< upper limit of normal (ULN) (ULN: 1.2 mg/dl) (or =< 3.0 mg/dL for patients with Gilbert’s syndrome)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 1.5 x ULN
- Serum creatinine =< 1.5 x ULN
- Willing to abstain from consumption of any supplements containing GTC
- Willing to restrict green tea consumption to less than three (3) servings of hot green tea or three (3) servings of iced green tea per week
- Willing to discontinue current vitamin/mineral supplement use containing green tea catechins (vitamin/mineral supplement will be provided)
- 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)
- Patients who have PCa 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 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
Additional locations may be listed on ClinicalTrials.gov for NCT04300855.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To assess the rate of clinical progression in men on active surveillance for prostate cancer (Gleason score [GS] 3+3 OR predominant Gleason grade 3 [3+4], =< 33% of biopsy cores positive for cancer and =< 50% involvement of any one core), treated with standardized green tea catechins (GTC) (400 mg epigallocatechin gallate [EGCG] twice daily [BID]) versus [vs.] placebo for 24 months.
SECONDARY OBJECTIVES:
I. Assess the safety of GTC (vs. placebo) safety by evaluating:
Ia. Incidence of adverse events and toxicities monitored using Common Toxicity Criteria version 5.0 (monthly).
Ib. Complete blood count (CBC), and comprehensive metabolic panel (CMP) at baseline, month 6, month 12, 18 and month 24 (end of intervention [EOI]).
Ic. Liver toxicities (LFTs) from baseline, and q 3 months until end of intervention (EOI).
II. Assess adherence and acceptability to agent by evaluating monthly percentage compliance using agent logs (%) and pill counts quarterly.
III. Assess change in prostate specific antigen (PSA) and PSA kinetics (PSA and PSA doubling time at month 12 and at 24 months) from serum at baseline, 6, 12, 18 and month 24 (EOI).
IV. Assess the proportion of men with no cancer in the post-intervention biopsy from baseline to month 24 (EOI).
OTHER OUTCOME OBJECTIVES:
I. Assess the change in gene expression panel (Decipher) (optional - if not standard of care [SOC] or covered by insurance) and a set of 13 biomarker genes known to be overexpressed in prostate cancer (PCa) from baseline to EOI using biopsy tissue.
II. Assess bioavailability as indicated by change in catechin (EGCG) measured in plasma at baseline, month 12, and month 24 (EOI).
III. Assess patient reported symptoms by evaluating change in scores in lower urinary tract symptoms (LUTS) from baseline to EOI; baseline, month 12 and month 24 (EOI).
IV. Assess patient reported symptoms by evaluating change in scores for Expanded Prostate Cancer Index Composite (EPIC) from baseline to EOI; baseline, month 12 and month 24 (EOI).
V. Assess patient reported symptoms by evaluating change in scores in quality of life (Short Form 36 Health Survey Standard [SF36]) from baseline to EOI at baseline, month 12 and month 24 (EOI).
VI. Assess changes in microbiome using stool samples from baseline to EOI.
VII. Assess change in biomarkers of proliferation and apoptosis Ki-67, apoptosis and NF-kB signaling in biopsy tissue from baseline and EOI.
VIII. With consent of participating subjects, create a specimen repository (serum, stool and prostate biopsies) to test future hypotheses related to prostate cancer, as and when possible.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive GTC orally (PO) twice daily (BID) for 24 months in the absence of disease progression or unacceptable toxicity. Patients may also undergo blood sample collection, tissue biopsy and digital rectal examination (DRE) throughout study.
GROUP II: Patients receive placebo PO BID for 24 months in the absence of disease progression or unacceptable toxicity. Patients may also undergo blood sample collection, tissue biopsy and DRE throughout study.
After completion of study treatment, patients are followed up at 7 days and then at 6 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMoffitt Cancer Center
Principal InvestigatorNagi B. Kumar
- Primary IDMCC-20056
- Secondary IDsNCI-2020-01751
- ClinicalTrials.gov IDNCT04300855