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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00596011
First received: January 7, 2008
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

The clinical study is a Phase II, randomized, double-blinded, placebo-controlled trial in men 30-80 years of age with biopsy proven HGPIN or atypical small acinar proliferation (ASAP) and no evidence of prostate cancer, prostatitis or urinary tract infection. A total of 272 men will be randomized to the study, with the goal of completing 240 evaluable participants. Participants who consent to the study and meet initial eligibility criteria will be undergo a one-week run-in period during which they will be asked to self-administer the supplement daily as well as complete study logs and two-day diet recall forms. Participants must meet all inclusion criteria and remain compliant during the run-in period to be randomized to a treatment arm. Participant will complete a quality of life (QOL) survey and have blood collected for baseline tests. Participants will be equally randomized (n=136 per arm) to blinded treatment with either Polyphenon E 200 mg epigallocatechin gallate (EGCG) twice a day (bid) or matching placebo. The planned intervention period is 12 months; participants will return for monthly clinic visits during the intervention period. After 3 and 6 months of intervention, blood will be drawn for serum chemistry and hematology, and other and lower urinary tract symptom (LUTS) and QOL assessments will be performed. In addition, at the 6 month visit, two-day diet recall forms will be collected, blood and urine will be collected, and repeat digital rectal exam (DRE) and prostatic 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. At the end of intervention (maximum of 12 months), a repeat prostate biopsy will be performed for post-intervention endpoint measurements. The primary endpoint of the study is a comparison of the incidence of prostate cancer between participants in the treatment vs. placebo arm; in addition, the prevalence of HGPIN or ASAP in pre-treatment and post-treatment biopsies in participants treated with Polyphenon E vs. placebo will be compared. If participants develop prostate cancer during the course of the study, the extent and grade of cancer will be assessed and compared between treatment groups.


Condition Intervention Phase
Prostatic Hyperplasia
Drug: Polyphenon E
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Rate of Progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Rate of progression to prostate cancer at one year in men treated with Polyphenon E (200 mg EGCG twice a day [bid]) following diagnosis of HGPIN or ASAP

  • Safety of Polyphenon E [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Safety of Polyphenon E (200 mg EGCG bid for one year) in men with HGPIN or ASAP

  • Effect of Polyphenon E Treatment on Quality of Life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Evaluate the effect of Polyphenon E treatment on LUTS and QOL in men diagnosed with HGPIN or ASAP


Secondary Outcome Measures:
  • Effect of Polyphenon E ABCA5 and PCADM-1 [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    The effect of Polyphenon E treatment on levels of ABCA5 in urine and PCADM-1 in serum

  • Effect of Polyphenon E on the Fundamental Molecular Pathways [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Explore the effects of Polyphenon E on the fundamental molecular pathways contributing to chemopreventive activity of Polyphenon E in the prostate


Enrollment: 100
Study Start Date: December 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Polyphenon E Treatment
Polyphenon E, 200 mg EGCG bid
Drug: Polyphenon E
Polyphenon E, 200 mg EGCG bid
Placebo Comparator: Placebo Administration
matching placebo
Drug: placebo
matching placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 subject 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00596011

Locations
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
LSU Health Sciences Center, Feist-Weiller Cancer Center
Shreveport, Louisiana, United States, 71130
Overton Brooks VA Medical Center
Shreveport, Louisiana, United States, 71101-4295
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
Investigators
Principal Investigator: Nagi Kumar, PhD H. Lee Moffitt Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00596011     History of Changes
Other Study ID Numbers: MCC-15008, R01 CA12060-01A1
Study First Received: January 7, 2008
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
PIN
polyphenon E
EGCG

Additional relevant MeSH terms:
Prostatic Hyperplasia
Neoplasms
Hyperplasia
Prostatic Intraepithelial Neoplasia
Carcinoma in Situ
Prostatic Diseases
Genital Diseases, Male
Pathologic Processes
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on April 22, 2014