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Study of Polyphenon E in Men With High-grade Prostatic Intraepithelial Neoplasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00596011
Recruitment Status : Completed
First Posted : January 16, 2008
Results First Posted : September 3, 2014
Last Update Posted : October 4, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief Summary:
The purpose of this study was to determine whether the daily consumption of decaffeinated green tea catechins (Polyphenon E®) for 1 year reduces the rate of progression to prostate cancer (PCa) in men diagnosed with HGPIN or ASAP. The aim was to recruit and treat 240 (120 men/arm) men diagnosed with the prostate condition HGPIN or ASAP with a capsule form of standardized green tea extract called Polyphenon E or placebo for a 12-month period and see if it can prevent progression of the prostate condition to prostate cancer. Investigators wanted to see if Polyphenon E reduces lower urinary tract symptoms and if this can be taken safely over one year. Investigators wanted to study how Polyphenon E is able to slow the progression to prostate cancer, or the mechanism of action of Polyphenon E. If the safety and the effects of Polyphenon E on slowing down the progression of prostate cancer is shown in our study, this will be a safe way of treating men who are at high risk or men like you who have a prostate condition that increases your chances of getting prostate cancer, so that we can prevent prostate cancer in the future.

Condition or disease Intervention/treatment Phase
Prostatic Hyperplasia Drug: Polyphenon E Drug: Placebo Phase 2

Detailed Description:
At the baseline/randomization visit, a QOL (Medical Outcomes Study Short Form-36) and lower urinary tract symptoms (LUTS) score assessment will be completed; urine and serum will be collected for measurement of diagnostic markers; plasma will be collected for measurement of baseline catechin levels; serum will be collected for banking; and diet recall forms will be collected. Participants will be equally randomized to blinded treatment with either Polyphenon E 200 mg EGCG bid or matching placebo, and an initial supply of study drug will be dispensed. All participants will also be provided with a standard multivitamin/mineral supplement to assure consistent, appropriate nutrient intake among study participants. The planned intervention period is 12 months; participants will return for monthly clinic visits during the intervention period. At each monthly clinic visit, blood will be drawn for repeat hepatic function panel, lactate dehydrogenase (LDH) and prothrombin time/partial thromboplastin time (PT/PTT), and participants will be interviewed to review and capture information from study agent intake log (pill count), assess signs and symptoms and concomitant medications; additional study medication will be dispensed as needed. After 3 and 6 months of intervention, blood will be drawn for serum chemistry and hematology, and LUTS and QOL assessments will be performed. In addition, at the 6 month visit, two-day diet recall forms will be collected, blood will be drawn for plasma catechin measurements and serum banking, serum and urine will be collected for diagnostic marker measurement, and repeat digital rectal exam (DRE) and prostate specific antigen (PSA) will be performed. If there is a palpable prostate nodule or confirmed PSA increase (>0.75 ng/ml) at 6 months, a repeat biopsy will be performed. If the 6-month biopsy shows evidence of disease progression, participants will stop intervention and proceed to the post-intervention assessment; otherwise, intervention will continue through month 12. At the end of intervention (maximum of 12 months), a repeat prostate biopsy will be performed for post-intervention endpoint measurements. In addition, the physical exam and DRE, LUTS and QOL will be repeated, and 2-day diet recall forms will be collected. Blood will be drawn for serum chemistry and hematology, PSA, hepatic function panel, LDH, PT/PTT; serum and urine will be collected for diagnostic marker measurement; plasma will be collected for catechin measurements; and serum will be collected for banking. Participants will be interviewed to review and capture information from study agent intake log (pill count), assess signs and symptoms and concomitant medications.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 97 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase II, Randomized, Double-blind, Multi-centered Study of Polyphenon E in Men With High-grade Prostatic Intraepithelial Neoplasia (HGPIN) or Atypical Small Acinar Proliferation (ASAP)
Actual Study Start Date : November 14, 2007
Actual Primary Completion Date : March 25, 2014
Actual Study Completion Date : July 27, 2018

Arm Intervention/treatment
Active Comparator: Polyphenon E Treatment
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Drug: Polyphenon E
Polyphenon E, at a dose of 400 mgs EGCG (200 mgs BID) for 1 year in men diagnosed with HGPIN and ASAP.
Other Names:
  • green tea catechins
  • PolyE

Placebo Comparator: Placebo Administration
Matching placebo BID
Drug: Placebo
Matching placebo BID

Primary Outcome Measures :
  1. Rate of Progression to Prostate Cancer (PCa) [ Time Frame: 12 months ]
    Number of participants with diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) who progressed to prostate cancer (PCa) at one year.

  2. Rate of Progression From HGPIN to ASAP or PCa [ Time Frame: 12 months ]
    Analyses of participants reaching a definitive endpoint. Number of baseline HGPIN participants who progressed to ASAP or PCa.

Secondary Outcome Measures :
  1. Treatment Emergent Adverse Events (AEs) [ Time Frame: 12 months ]
    Safety of Polyphenon E (200 mg EGCG bid for one year) in men with HGPIN or ASAP. Number of participants with AEs Possibly or Probably related to treatment.

  2. Occurrence of Grade 3 or Higher Adverse Events (AEs) [ Time Frame: 12 months ]
    Number of participants with AEs grade 3 or higher, per treatment arm.

  3. Median Serum Total Prostatic Specific Antigen (tPSA) [ Time Frame: 12 months ]
    Median ng/mL serum tPSA post treatment, per treatment arm.

Other Outcome Measures:
  1. Change in Scores - Lower Urinary Tract Symptom (LUTS) [ Time Frame: 1 year ]
    Change in score from baseline to 1 year. LUTS represent a common conglomeration of storage, voiding, and post-micturition symptoms with reported debilitating effect on quality of life. Symptom severity related to urinary frequency, nocturia, weak urinary stream, hesitancy, intermittency, incomplete bladder emptying and urinary urgency are assessed. We utilized the American Urological Association Symptom Score for the evaluation LUTS in this patient population. Symptom Frequency Scores: 0 = Not at all, 1 = Less than 1 time in 5, 2 = Less than half the time, 3 = About half the time, 4 = More than half the time, 5 = Almost always. Total Symptom Score = Sum of individual scores of the 7 symptoms. (minimum possible score=0; maximum possible score =35; Range of scores and significance: 0-7 mild symptoms; 8-19 moderate symptoms; 20-35 severe symptoms.

  2. Effect of Polyphenon E on the Fundamental Molecular Pathways [ Time Frame: 12 months ]
    Explore the effects of Polyphenon E on the fundamental molecular pathways contributing to chemopreventive activity of Polyphenon E in the prostate. This exploratory aim is ongoing.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men with a diagnosis of HGPIN or ASAP in a minimum of 1 of 8 cores from a biopsy performed within six months of study entry. Diagnosis of HGPIN or ASAP (which includes men with ASAP and HGPIN) via trans-rectal ultrasound (TRUS biopsy) is also considered acceptable for inclusion.
  • Prostate biopsy with a minimum of 8 cores performed within 6 months of study entry that shows no evidence of cancer.
  • 30-80 years of age at the time of registration
  • PSA ≤10 ng/ml
  • Omnivorous diet
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Participants must have normal organ and marrow function as demonstrated by the following parameters being within normal institutional limits: complete blood count (CBC); liver function tests (LFTs); albumin, total and direct bilirubin, alkaline phosphatase, aspartic transaminase (AST), alanine transaminase (ALT), and total protein), PT/PTT, and LDH; serum creatinine <1.5 mg/dl or measured creatinine clearance 60 cc/min
  • Absence of consumption of toremifene citrate, finasteride, testosterone, dehydroepiandrosterone (DHEA) or other testosterone-like supplements or medications which have known impact on PSA within 30 days of informed consent, or dutasteride within 90 days of informed consent
  • Absence of consumption of any nutritional or herbal supplements containing green tea or green tea polyphenols
  • No or low regular tea consumption (no more than 3 servings of hot tea or 6 servings of iced tea per week)
  • Willing to discontinue current vitamin/mineral supplement use and substitute with a standard multivitamin supplement provided for the study
  • Willing to use an effective method of contraception, if the partner is of child-bearing age, while on study
  • Willing to comply with proposed visit and treatment schedule
  • Able to understand and willing to sign a written informed consent document

Exclusion Criteria:

  • Evidence of acute prostatitis or urinary tract infection at the time of PSA measurement; men may be enrolled 30 days after completion of treatment, provided all other eligibility criteria are met
  • Current or prior history of prostate cancer or other malignancies (exceptions include non-melanoma skin cancer or other cancer with no evidence of tumor recurrence 5 years after definitive treatment)
  • History of renal or hepatic disease, including history of hepatitis B, C or delta
  • Participation in any other investigational study or use of any other investigational agents within 30 days of study entry
  • History of allergic reactions attributed to tea or other compounds of similar chemical or biologic composition to Polyphenon E or the inactive components present in Polyphenon E and placebo capsules.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any psychological, familial, sociological or other concomitant condition that would not allow adequate compliance with the study protocol
  • History of medical conditions that may predispose the participant to gastrointestinal bleeding (acute or chronic gastritis or colitis, or acute diverticulitis or hemorrhoids)
  • Members of all races and ethnic groups are eligible for this trial. Since this is an investigation targeting men with HGPIN or ASAP, women are not eligible for the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00596011

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United States, Florida
University of Florida/Shands-Department of Urology
Gainesville, Florida, United States, 32610
University of Florida - Jacksonville
Jacksonville, Florida, United States, 32209
Watson Clinic Center for Research, Inc.
Lakeland, Florida, United States, 33805
H Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
James A Haley VA
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago - Department of Surgery
Chicago, Illinois, United States, 60637
United States, Louisiana
Overton Brooks VA Medical Center
Shreveport, Louisiana, United States, 71101-4295
LSU Health Sciences Center, Feist-Weiller Cancer Center
Shreveport, Louisiana, United States, 71130
United States, Minnesota
Minneapolis VA Medical Center
Minneapolis, Minnesota, United States, 55417
United States, Pennsylvania
Jefferson Medical College - Department of Urology
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
National Cancer Institute (NCI)
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Principal Investigator: Nagi Kumar, PhD H. Lee Moffitt Cancer Center
Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT00596011    
Other Study ID Numbers: MCC-15008
R01CA12060-01A1 ( Other Identifier: NIH )
First Posted: January 16, 2008    Key Record Dates
Results First Posted: September 3, 2014
Last Update Posted: October 4, 2019
Last Verified: October 2019
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
prostate cancer
polyphenon E
Additional relevant MeSH terms:
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Prostatic Intraepithelial Neoplasia
Prostatic Hyperplasia
Pathologic Processes
Prostatic Diseases
Carcinoma in Situ
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type