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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIPreventionClosed30 to 80NCI, OtherMCC-15008
R01 CA12060-01A1, NCT00596011

Trial Description

Summary

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.

Further Study Information

This clinical study is a Phase II, randomized, double-blinded, placebo-controlled trial in men 30-80 years of age with biopsy proven HGPIN 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. Presence of HGPIN and absence of prostate cancer will be confirmed from a diagnostic biopsy with a minimum of 12 core biopsies. When possible, samples from the diagnostic biopsy will be used for baseline endpoint measurements (proteasome inhibition, Ki-67, apoptotic index, exploratory mechanistic studies) and for tissue banking (if a participant consents). Screening tests will also include a Demographic Questionnaire, physical exam, DRE, blood chemistry and hematology, prothrombin time/partial thromboplastin time (PT/PTT), lactose dehydrogenase (LDH), hepatic function panel and serum PSA. Participants who consent to the study and meet initial eligibility criteria will be provided with a seven-day multivitamin/mineral supplement, and will 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. At the baseline/randomization visit, a Medical Outcomes Study Short Form-36 (QOL)and 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 (n=136 per arm) 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, LDH and 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 three and six 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 DRE and 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 six-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 two-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. 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 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. Other endpoints include: assessing the safety of Polyphenon E under the proposed dosing regimen; investigating the effect of Polyphenon E treatment on proteasome activity (chymotrypsin-like activity, IκBα protein expression, accumulation of p27 proteins, NFκB binding activity), cell proliferation (Ki-67) and apoptosis (TUNEL) in prostate tissue biopsy samples; correlating changes in proteasome activity with proliferation and apoptosis; evaluating the potential of ABCA5 level in urine and PCADM-1 level in serum as markers of HGPIN and prostate cancer, respectively; and evaluating effects of Polyphenon E on these putative diagnostic markers. Additional exploratory endpoints include treatment-related stabilization and accumulation of tumor suppressor p53 and pro-apoptotic protein Bax, inhibition of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). It is anticipated that approximately 40 months will be required to enroll all participants; the entire study is expected to take 60 months to complete.

Eligibility 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.

Trial Contact Information

Trial Lead Organizations/Sponsors

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

National Cancer Institute

Nagi B. KumarPrincipal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00596011
ClinicalTrials.gov processed this data on April 03, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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