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

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ClinicalTrials.gov Identifier: NCT00596011
Recruitment Status : Completed
First Posted : January 16, 2008
Results First Posted : September 3, 2014
Last Update Posted : May 3, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Prostatic Hyperplasia
Interventions Drug: Polyphenon E
Drug: Placebo
Enrollment 97
Recruitment Details Participants were enrolled at the Moffitt Cancer Center and 7 other sites in the United States, from September 2008- March 2013.
Pre-assignment Details Participants were block randomized by diagnosis to receive Polyphenon E®) (PolyE) containing 400 mgs (−)-epigallocatechin-3-gallate (EGCG) per day (n=49) or placebo (n=48) for 1 year.
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID) Matching placebo twice a day (BID)
Period Title: Overall Study
Started 49 48
Completed 36 38
Not Completed 13 10
Reason Not Completed
Withdrawal by Subject             2             3
Adverse Event             11             7
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration Total
Hide Arm/Group Description Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID) Matching placebo twice a day (BID) Total of all reporting groups
Overall Number of Baseline Participants 49 48 97
Hide Baseline Analysis Population Description
All participants
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 49 participants 48 participants 97 participants
62
(45 to 79)
64.10
(45 to 78)
63.02
(45 to 79)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 48 participants 97 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
27
  55.1%
25
  52.1%
52
  53.6%
>=65 years
22
  44.9%
23
  47.9%
45
  46.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants 48 participants 97 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
49
 100.0%
48
 100.0%
97
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 49 participants 48 participants 97 participants
49
 100.0%
48
 100.0%
97
 100.0%
1.Primary Outcome
Title Rate of Progression to Prostate Cancer (PCa)
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description:
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Matching placebo twice a day (BID)
Overall Number of Participants Analyzed 49 48
Measure Type: Number
Unit of Measure: participants
4 6
2.Primary Outcome
Title Rate of Progression From HGPIN to ASAP or PCa
Hide Description Analyses of participants reaching a definitive endpoint. Number of baseline HGPIN participants who progressed to ASAP or PCa.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Baseline HGPIN participants
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description:
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Matching placebo twice a day (BID)
Overall Number of Participants Analyzed 26 25
Measure Type: Number
Unit of Measure: participants
Progressed to ASAP or PCa 3 10
Progressed to ASAP 0 5
3.Secondary Outcome
Title Treatment Emergent Adverse Events (AEs)
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description:
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Matching placebo twice a day (BID)
Overall Number of Participants Analyzed 49 48
Measure Type: Number
Unit of Measure: participants
Definitely related to treatment 0 0
Probably related to treatment 5 1
Possibly related to treatment 7 3
Unlikely to be related to treatment 7 9
Unrelated to treatment 193 156
Total 212 169
4.Secondary Outcome
Title Occurrence of Grade 3 or Higher Adverse Events (AEs)
Hide Description Number of participants with AEs grade 3 or higher, per treatment arm.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description:
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Matching placebo twice a day (BID)
Overall Number of Participants Analyzed 49 48
Measure Type: Number
Unit of Measure: participants
10 3
5.Secondary Outcome
Title Median Serum Total Prostatic Specific Antigen (tPSA)
Hide Description Median ng/mL serum tPSA post treatment, per treatment arm.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description:
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Matching placebo twice a day (BID)
Overall Number of Participants Analyzed 49 48
Median (95% Confidence Interval)
Unit of Measure: ng/mL
3.5
(2.80 to 5.10)
4.90
(3.65 to 6.15)
6.Other Pre-specified Outcome
Title Change in Scores - Lower Urinary Tract Symptom (LUTS)
Hide Description 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.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with LUTS symptom scores available at baseline and at one year
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description:
Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID)
Matching placebo twice a day (BID)
Overall Number of Participants Analyzed 29 28
Mean (Standard Deviation)
Unit of Measure: units on a scale
Incomplete empty - change 0.07  (1.77) 0.39  (1.99)
Frequent urination - change 0.03  (1.61) 0.50  (1.45)
Intermittency - change 0.21  (1.32) -0.04  (1.4)
Nocturia - change 0.31  (1.42) 0.25  (1.69)
Straining - change 0.24  (0.99) 0.25  (0.97)
Urgency - change 0.10  (1.47) -0.25  (1.86)
Weak stream 0.24  (1.12) 0.15  (1.49)
Total Symptom Score - change 1.21  (6.56) 1.36  (7.93)
7.Other Pre-specified Outcome
Title Effect of Polyphenon E on the Fundamental Molecular Pathways
Hide Description 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.
Time Frame 12 months
Outcome Measure Data Not Reported
Time Frame Average of 12 months
Adverse Event Reporting Description All participants. All adverse events, regardless of causality.
 
Arm/Group Title Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Hide Arm/Group Description Polyphenon E, 200 mg epigallocatechin gallate (EGCG) twice a day (BID) Matching placebo twice a day (BID)
All-Cause Mortality
Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/49 (8.16%)      2/48 (4.17%)    
Cardiac disorders     
Supraventricular and nodal arrhythmia - Supraventricular tachycardia  1  1/49 (2.04%)  1 0/48 (0.00%)  0
Ventricular arrhythmia - Ventricular tachycardia  1  1/49 (2.04%)  1 0/48 (0.00%)  0
Cardiac General - Other - Atrial Fibrillation  1  0/49 (0.00%)  0 1/48 (2.08%)  1
Gastrointestinal disorders     
Perforation, GI - Small bowel NOS  1  0/49 (0.00%)  0 1/48 (2.08%)  1
General disorders     
Death not associated with CTCAE term - Death NOS  1  1/49 (2.04%)  1 0/48 (0.00%)  0
Infections and infestations     
Infection with unknown ANC - Wound  1  1/49 (2.04%)  1 0/48 (0.00%)  0
Renal and urinary disorders     
Obstruction, GU - Bladder  1  1/49 (2.04%)  1 0/48 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Active Comparator: Polyphenon E Treatment Placebo Comparator: Placebo Administration
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   47/49 (95.92%)      44/48 (91.67%)    
Blood and lymphatic system disorders     
Blood/Bone Marrow - Other  1  11/49 (22.45%)  20 16/48 (33.33%)  26
Hemoglobin  1  4/49 (8.16%)  4 3/48 (6.25%)  3
Gastrointestinal disorders     
Gastrointestinal - Other  1  7/49 (14.29%)  9 5/48 (10.42%)  8
Nausea  1  6/49 (12.24%)  8 0/48 (0.00%)  0
Flatulence  1  3/49 (6.12%)  4 1/48 (2.08%)  1
General disorders     
Pain - Head/headache  1  10/49 (20.41%)  13 2/48 (4.17%)  8
Pain - Extremity-limb  1  3/49 (6.12%)  5 1/48 (2.08%)  1
Constitutional Symptoms - Other  1  4/49 (8.16%)  4 7/48 (14.58%)  11
Fatigue (asthenia, lethargy, malaise)  1  3/49 (6.12%)  3 2/48 (4.17%)  2
Investigations     
Coagulation - Other  1  7/49 (14.29%)  13 3/48 (6.25%)  8
PTT (Partial Thromboplastin Time)  1  5/49 (10.20%)  6 2/48 (4.17%)  2
INR (International Normalized Ratio of prothrombin time)  1  4/49 (8.16%)  6 0/48 (0.00%)  0
Metabolism and nutrition disorders     
Metabolic/Laboratory - Other  1  23/49 (46.94%)  53 26/48 (54.17%)  61
Glucose, serum-high (hyperglycemia)  1  13/49 (26.53%)  14 8/48 (16.67%)  8
Glucose, serum-low (hypoglycemia)  1  8/49 (16.33%)  8 9/48 (18.75%)  9
AST, SGOT(serum glutamic oxaloacetic transaminase)  1  7/49 (14.29%)  10 6/48 (12.50%)  8
ALT, SGPT (serum glutamic pyruvic transaminase)  1  4/49 (8.16%)  8 3/48 (6.25%)  3
Bilirubin (hyperbilirubinemia)  1  3/49 (6.12%)  8 2/48 (4.17%)  7
Calcium, serum-high (hypercalcemia)  1  1/49 (2.04%)  1 3/48 (6.25%)  4
Creatinine  1  3/49 (6.12%)  3 1/48 (2.08%)  1
Musculoskeletal and connective tissue disorders     
Musculoskeletal/Soft Tissue - Other  1  8/49 (16.33%)  11 2/48 (4.17%)  2
Renal and urinary disorders     
Renal/Genitourinary - Other  1  8/49 (16.33%)  11 10/48 (20.83%)  14
Urinary frequency/urgency  1  2/49 (4.08%)  3 3/48 (6.25%)  3
Respiratory, thoracic and mediastinal disorders     
Pulmonary/Upper Respiratory - Other  1  6/49 (12.24%)  6 6/48 (12.50%)  8
Cough  1  0/49 (0.00%)  0 3/48 (6.25%)  4
Allergic rhinitis  1  2/49 (4.08%)  2 3/48 (6.25%)  3
Skin and subcutaneous tissue disorders     
Dermatology/Skin - Other  1  4/49 (8.16%)  5 2/48 (4.17%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Primary Endpoint: Progression to PCa. Recent evidence demonstrates ASAP is a stronger diagnostic predictor associated with PCa compared to HGPIN. Due to this evidence and recruitment challenges, we revised inclusion criteria to include men with ASAP.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Nagi Kumar, Ph.D.
Organization: H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-6885
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00596011     History of Changes
Other Study ID Numbers: MCC-15008
R01CA12060-01A1 ( Other Identifier: NIH )
First Submitted: January 7, 2008
First Posted: January 16, 2008
Results First Submitted: August 15, 2014
Results First Posted: September 3, 2014
Last Update Posted: May 3, 2019