To Evaluate if Green Tea Can be Effective in Reducing the Progression of Prostate Cancer in Men on Close Monitoring

• ClinicalTrials.gov Identifier: NCT04597359
• Recruitment Status: Recruiting
• First Posted: October 22, 2020
• Last Update Posted: August 12, 2022
• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Tracking Information

• First Submitted Date: October 14, 2020
• First Posted Date: October 22, 2020
• Last Update Posted Date: August 12, 2022
• Actual Study Start Date: May 20, 2021
• Estimated Primary Completion Date: June 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 20, 2020)

Change in the highest percent Ki-67 expression [ Time Frame: Baseline to 6 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 20, 2020)

• Apoptosis [ Time Frame: Up to 6 months ]
  Will be assessed by caspase in tumor tissue from EOS biopsy by treatment.
• Apoptosis ratio [ Time Frame: Up to 6 months ]
  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.
• Number of biopsy cores positive for cancer at end of study [ Time Frame: At 6 months ]
  Descriptive statistics with confidence intervals will be presented. For binary measures, will use Fisher's test.
• Percent of any biopsy tissue core positive for cancer at end of study [ Time Frame: At 6 months ]
  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.
• Percent Ki-67 [ Time Frame: Up to 6 months ]
  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.
• Gleason sum at end of study [ Time Frame: At 6 months ]
  Descriptive statistics with confidence intervals will be presented. For binary measures, will use Fisher's test.
• Change in serum prostate-specific antigen (PSA) [ Time Frame: Baseline up to 6 months ]
  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.
• Incidence of adverse events [ Time Frame: Up to 12 months ]
  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.
• Change in geometric mean of percent Ki-67 [ Time Frame: Baseline up to 6 months ]
  Descriptive statistics with confidence intervals will be presented. For binary measures, will use Fisher's test.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 20, 2020)

• Compliance to study drug (standard pill counts) [ Time Frame: Up to 6 months ]
  Compliance to study drug will be evaluated by standard pill counts. Will evaluate percentage compliance to study agent in the study arms using pill counts.
• Compliance to study drug (diet records) [ Time Frame: Up to 6 months ]
  Compliance to study drug will be evaluated by diet records.
• Compliance to study drug (plasma concentrations of GTC) [ Time Frame: Up to 6 months ]
  Compliance to study drug will be evaluated by plasma concentrations of GTC (epigallocatechin gallate [EGCG]). For plasma, will assess the change from baseline to end of treatment for GTC (EGCG) to estimate compliance and bioavailability.
• Epigallocatechin gallate (EGCG) concentrations [ Time Frame: Up to 6 months ]
  Will correlate EGCG concentrations with prostate specific antigen density (PSAD) and prostate specific antigen doubling time (PSADT), using descriptive analysis with scatter plots and regression analysis, and adjusting intervention and known predictors including the stratification factors in multivariable analysis. Will transform to the square root or logarithmic transformation of the data to improve normality of the distributions (determined as the transformation (including untransformed) with the lowest Anderson-Darling normality score).
• Changes in lower urinary tract symptoms (LUTS) [ Time Frame: Baseline up to 6 months ]
  Lower urinary tract symptoms (LUTS) will be assessed using the American Urological Association Symptom Score for the evaluation, LUTS Symptom Scale. The highest score on the scale is 5, "almost always" and the lowest score on the scale is 0, "not at all".
• Changes in lower urinary tract symptoms [ Time Frame: Baseline up to 6 months ]
  Will assess change in EGCG from baseline to EOS, adherence to GTC, and bioavailability of GTC from baseline to EOS by treatment.
• Changes in quality of life (QOL) [ Time Frame: Baseline up to 6 months ]
  Quality of life will be assessed using the Functional Assessment of Cancer Therapy (FACT)-Prostate.
• Changes in quality of life (QOL) [ Time Frame: Baseline up to 6 months ]
  Will assess change in EGCG from baseline to EOS, adherence to GTC, and bioavailability of GTC from baseline to EOS by treatment.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: To Evaluate if Green Tea Can be Effective in Reducing the Progression of Prostate Cancer in Men on Close Monitoring
• Official Title: 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
• Brief Summary: 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.

Detailed Description

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Prostate Carcinoma

Intervention

• Drug: Placebo Administration
  Given PO
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Other: Questionnaire Administration
  Ancillary studies
• Drug: Sinecatechins
  Given PO
  Other Names:

  • Camellia sinensis Leaf Catechins
  • Kunecatechins
  • Polyphenon E
  • Polyphenon E TM
  • Veregen

Study Arms

• Experimental: Arm A (green tea catechins)
  Patients receive green tea catechins PO BID for up to 6 months in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
  • Drug: Sinecatechins
• Placebo Comparator: Arm B (placebo)
  Patients receive placebo PO BID for up to 6 months.
  Interventions:

  • Drug: Placebo Administration
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 20, 2020): 360
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2026
• Estimated Primary Completion Date: June 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

    • H. Lee Moffitt Cancer Center & Research Institute will perform Gleason score confirmation and % Ki-67 expression (5% or more) in tumor tissue and notify the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) Operations Office and submitting institution within 3-4 business days of receipt of the tumor tissue specimen
• 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:

• EXCLUSION CRITERIA FOR PREREGISTRATION (STEP 0: SCREENING)
• 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 a history of renal or hepatic disease, including history of hepatitis B and C
• 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. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: Guam, United States

Administrative Information

• NCT Number: NCT04597359
• Other Study ID Numbers: EA8184; NCI-2020-07173 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); EA8184 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); ECOG-ACRIN-EA8184 ( Other Identifier: DCP ); EA8184 ( Other Identifier: CTEP ); UG1CA189828 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
• Original Responsible Party: Same as current
• Current Study Sponsor: ECOG-ACRIN Cancer Research Group
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nagi B Kumar; ECOG-ACRIN Cancer Research Group

• PRS Account: Eastern Cooperative Oncology Group
• Verification Date: August 2022