Back to resultsPomegranate-Extract Pill in Preventing Tumor Growth in Patients With Localized Prostate Cancer Undergoing Active Surveillance
Primary Purpose
PSA Level Less Than or Equal to Fifteen, PSA Level Less Than Ten, Stage I Prostate Cancer AJCC v7
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Pharmacological Study
Placebo
Pomegranate-Extract Pill
Sponsored by
About this trial
This is an interventional prevention trial for PSA Level Less Than or Equal to Fifteen
Eligibility Criteria
Inclusion Criteria:
- Participants must have had a standard-of-care biopsy within 13 months of the baseline study visit and must have been diagnosed with low-grade, clinically localized prostate cancer (Gleason score =< 3+3 with a PSA at baseline < 10 ng/ml in participants < 70 years of age, OR Gleason score =< 3+4 with a PSA at baseline =< 15 ng/ml in participants >= 70 years of age); eligible participants will be those men who are able and willing to undergo AS with PSA monitoring and a scheduled biopsy performed at the end of the study
- No concurrent treatment (hormonal, radiation or systemic chemotherapy) for prostate cancer during study enrollment is planned (unless participants demonstrate clinical evidence of prostate cancer progression such as symptoms, physical exam findings, a rapidly increasing PSA, or radiologic findings which confirm disease progression)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- White blood cells (WBC) >= 3000/mm^3
- Platelets >= 100,000 mm^3
- Hemoglobin >= 10 g/dL
- Total bilirubin =< 1.5 x upper limit of institutional normal
- Alkaline phosphatase =< 1.5 x upper limit of institutional normal
- Aspartate aminotransferase (AST) =< 1.5 x upper limit of institutional normal
- Alanine aminotransferase (ALT) =< 1.5 x upper limit of institutional normal
- Serum creatinine within 1.5 x upper limit of institutional normal
- Sodium 135-144 mmol/L (inclusive)
- Potassium 3.2-4.8 mmol/L (inclusive)
- Participants will be required to use a medically-approved method of birth control or abstinence if their sexual partner is of child-bearing potential
- Participants must be willing to forego foods, beverages and supplements containing pomegranate for the duration of the study
- Ability to understand, and the willingness to sign, a written informed consent document
Exclusion Criteria:
- Any prior surgery to the prostate within 30 days of baseline procedures; NOTE: Biopsies are not considered surgeries
- Evidence of other cancer(s) (excluding non-melanoma skin cancer) within last 5 years
- Prior pelvic radiation for any reason
- Participants cannot be taking 5-alpha-reductase inhibitors while on study or within 6 months of the baseline study visit
- Participants may not be taking carbamazepine (tegretol)
- Participants may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PFE
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- Any significant cardiac event(s) within the 12 months prior to registration, such as episode(s) of symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris or persistent, stable angina pectoris, or cardiac arrhythmia requiring medication
Sites / Locations
- Lahey Hospital and Medical Center
- University of Minnesota/Masonic Cancer Center
- Urology San Antonio Research PA
- University of Wisconsin Hospital and Clinics
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group I (pomegranate-extract pill)
Group II (placebo)
Arm Description
Patients receive pomegranate-extract pill PO QD for 52 weeks (+/- 1 week).
Patients receive placebo PO QD for 52 weeks (+/- 1 week).
Outcomes
Primary Outcome Measures
Change in Plasma IGF-1 From Baseline to Post-Treatment
The primary endpoint for modulation of intermediate endpoint biomarkers will be the change in the plasma levels of IGF-1 by a quantitative assay (ELISA) from pre-study to post-treatment. The difference between these time points for the placebo group and the pomegranate fruit extract (PFE) group will be tested using a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test.
Secondary Outcome Measures
Compliance: Number of Participants Who Took Study Drug Per Protocol
Summarized by treatment arm with descriptive statistics, and tested for imbalance using Wilcoxon rank-sum test. Reported for each visit per protocol at Week 13, Week 26, Week 39, and Week 52 (end of study).
Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE)
Patient toxicity throughout the study will be summarized in several ways; the presence or absence of any toxicity, worst CTCAE grade, and strongest investigator-defined relationship will all be examined and characterized by treatment arm, and analyzed appropriately (Wilcoxon rank-sum for ordinal data, Fisher's exact test for dichotomous data, and log rank test for time to event data).
Change in Plasma Biomarker Levels From Baseline: IGFBP-3
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Total Serum Prostate Specific Antigen (PSA) From Baseline
Change in Serum Testosterone
Prostate Specific Antigen Doubling Time (PSA DT)
PSA DT will be determined from PSA values obtained during study participation (baseline and weeks 13, 26, 39 and 52). The secondary endpoint of PSA DT is based on the value at study completion (week 52 or at point of early termination). However, PSA DT will be determined starting at week 26 (the earliest time point with 3 values) and week 39 and recorded. PSA doubling time is a measure based on the slope of the PSA at multiple time points. If the slope is relatively flat, the predicted doubling time could be far beyond the length of the actual study. As such, the value is not limited to the time frame over which data is collected from the participant.
Change in Tissue Biomarker Levels: PSA
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Tissue Biomarker Levels: IGF-1
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Tissue Biomarker Levels: IGFBP-3
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Tissue Biomarker Levels: CASP3
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Tissue Biomarker Levels: Ki-67
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Tissue Biomarker Levels: IGF-Rb
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Tissue Biomarker Levels: 8OHdG
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Tissue Biomarker Levels: AR
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Levels of PFE Constituents/Metabolites: Urolithin B
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Change in Gleason Score
The Gleason Score is a grading system used to determine the aggressiveness of prostate cancer, scored 1-5 with 1 being healthy tissue and 5 being abnormal. Prostate cancers are assigned 2 scores to define the 2 most prevalent tissue types. They are added together (total range of 2-10). Typical scores fall between 6-10, the higher the overall score, the more likely the cancer will spread.
Change in Biopsy Tumor Involvement on Prostate Biopsy
Change in the length of biopsy cores that contained cancerous tissue from Baseline to end of study.
Full Information
NCT ID
NCT02095145
First Posted
March 20, 2014
Last Updated
January 31, 2020
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02095145
Brief Title
Pomegranate-Extract Pill in Preventing Tumor Growth in Patients With Localized Prostate Cancer Undergoing Active Surveillance
Official Title
A Phase IIA Exploratory, Randomized, Placebo-Controlled Trial of Pomegranate Fruit Extract/Pomx™ in Subjects With Clinically Localized Prostate Cancer Undergoing Active Surveillance
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
May 8, 2014 (Actual)
Primary Completion Date
January 23, 2018 (Actual)
Study Completion Date
September 26, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This randomized phase II trial studies pomegranate-extract pill in preventing tumor growth in patients with prostate cancer that is limited to a certain part of the body (localized), who have chosen observation as their treatment plan. The use of pomegranate-extract pill may slow disease progression in patients with localized prostate cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the effect of pomegranate fruit extract (PFE) 1000 mg, taken daily for 1 year, on the plasma levels of insulin-like growth factor (IGF-1) from baseline to end of study (52 weeks) in participants undergoing active surveillance (AS) for early stage prostate cancer.
SECONDARY OBJECTIVES:
I. To assess compliance with a once daily oral administration of PFE versus placebo over a 52-week period of time.
II. To assess the toxicity of PFE vs. placebo when taken daily for 52 weeks (+/- 1 week).
III. To compare and correlate the effect of 52 weeks of daily dosing with PFE vs placebo on the end of study biopsy results including the presence or absence of tumor, the extent of tumor and Gleason scores.
IV. To compare and correlate the modulation of the following biomarkers with response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core, tumor tissue from a positive core, and normal tissue adjacent to tumor from a positive core; plasma: insulin-like growth factor 1/IGF binding protein 3 ratio (IGF-1/IGFBP-3 ratio); prostate tissue (normal and abnormal): apoptosis (CASPASE 3), Ki-67, 8OHdG, IGF-1R, androgen receptor, IGF-1, IGFBP-3, prostate specific antigen (PSA).
V. Measure PFE constituents/metabolites in plasma and urine for evidence of accumulation (trough levels): ellagic acid, dimethyl ellagic acid, dimethyl ellagic acid glucuronide (DMEAG), urolithin A, urolithin A-glucuronide, urolithin B and urolithin B-glucuronide.
VI. Measure PSA doubling time (PSA DT) in serum, using the calculation provided on the Memorial Sloan Kettering Cancer Center website.
VII. To assess the feasibility of cancer chemoprevention trials in a population of men undergoing active surveillance for prostate cancer.
VIII. Measurement of serum testosterone.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive pomegranate-extract pill orally (PO) once daily (QD) for 52 weeks (+/- 1 week).
GROUP II: Patients receive placebo PO QD for 52 weeks (+/- 1 week).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PSA Level Less Than or Equal to Fifteen, PSA Level Less Than Ten, Stage I Prostate Cancer AJCC v7, Stage II Prostate Cancer AJCC v7, Stage IIA Prostate Cancer AJCC v7, Stage IIB Prostate Cancer AJCC v7
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group I (pomegranate-extract pill)
Arm Type
Experimental
Arm Description
Patients receive pomegranate-extract pill PO QD for 52 weeks (+/- 1 week).
Arm Title
Group II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO QD for 52 weeks (+/- 1 week).
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Pomegranate-Extract Pill
Other Intervention Name(s)
POMx
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Change in Plasma IGF-1 From Baseline to Post-Treatment
Description
The primary endpoint for modulation of intermediate endpoint biomarkers will be the change in the plasma levels of IGF-1 by a quantitative assay (ELISA) from pre-study to post-treatment. The difference between these time points for the placebo group and the pomegranate fruit extract (PFE) group will be tested using a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test.
Time Frame
Baseline to 12 months
Secondary Outcome Measure Information:
Title
Compliance: Number of Participants Who Took Study Drug Per Protocol
Description
Summarized by treatment arm with descriptive statistics, and tested for imbalance using Wilcoxon rank-sum test. Reported for each visit per protocol at Week 13, Week 26, Week 39, and Week 52 (end of study).
Time Frame
Up to 1 year
Title
Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE)
Description
Patient toxicity throughout the study will be summarized in several ways; the presence or absence of any toxicity, worst CTCAE grade, and strongest investigator-defined relationship will all be examined and characterized by treatment arm, and analyzed appropriately (Wilcoxon rank-sum for ordinal data, Fisher's exact test for dichotomous data, and log rank test for time to event data).
Time Frame
Up to 1 year
Title
Change in Plasma Biomarker Levels From Baseline: IGFBP-3
Description
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Week 13, Week 26, Week 39, Week 52
Title
Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3
Description
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Week 13, Week 26, Week 39, Week 52
Title
Change in Total Serum Prostate Specific Antigen (PSA) From Baseline
Time Frame
Up to 1 year
Title
Change in Serum Testosterone
Time Frame
up to 1 year
Title
Prostate Specific Antigen Doubling Time (PSA DT)
Description
PSA DT will be determined from PSA values obtained during study participation (baseline and weeks 13, 26, 39 and 52). The secondary endpoint of PSA DT is based on the value at study completion (week 52 or at point of early termination). However, PSA DT will be determined starting at week 26 (the earliest time point with 3 values) and week 39 and recorded. PSA doubling time is a measure based on the slope of the PSA at multiple time points. If the slope is relatively flat, the predicted doubling time could be far beyond the length of the actual study. As such, the value is not limited to the time frame over which data is collected from the participant.
Time Frame
up to 52 Weeks
Title
Change in Tissue Biomarker Levels: PSA
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Tissue Biomarker Levels: IGF-1
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Tissue Biomarker Levels: IGFBP-3
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Tissue Biomarker Levels: CASP3
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Tissue Biomarker Levels: Ki-67
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Tissue Biomarker Levels: IGF-Rb
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Tissue Biomarker Levels: 8OHdG
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Measurements for each are per nuclear ("Nuc" in results), cytoplasmic ("Cyt" in results), and cellular ("Cell" in results) basis. Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Tissue Biomarker Levels: AR
Description
Compare and correlate biomarker modulation in response to PFE versus placebo in three areas of interest: tissue from a completely benign biopsy core ("benign" in results), tumor tissue from a positive core ("tumor" in results), and normal tissue adjacent to tumor from a positive core ("adjacent" in results). Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Baseline to Week 52
Title
Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A
Description
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Change from Baseline at Week 13, Week 26, Week 39, and Week 52
Title
Change in Levels of PFE Constituents/Metabolites: Urolithin B
Description
Differences between the groups will be examined for the change from baseline with the appropriate tests; for dichotomous data Fisher's exact test will be used, for ordinal data Wilcoxon rank-sum test will be used, and for continuous data, and a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time Frame
Change from Baseline at Week 13, Week 26, Week 39, and Week 52
Title
Change in Gleason Score
Description
The Gleason Score is a grading system used to determine the aggressiveness of prostate cancer, scored 1-5 with 1 being healthy tissue and 5 being abnormal. Prostate cancers are assigned 2 scores to define the 2 most prevalent tissue types. They are added together (total range of 2-10). Typical scores fall between 6-10, the higher the overall score, the more likely the cancer will spread.
Time Frame
Baseline to 1 year
Title
Change in Biopsy Tumor Involvement on Prostate Biopsy
Description
Change in the length of biopsy cores that contained cancerous tissue from Baseline to end of study.
Time Frame
Baseline to 1 year
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must have had a standard-of-care biopsy within 13 months of the baseline study visit and must have been diagnosed with low-grade, clinically localized prostate cancer (Gleason score =< 3+3 with a PSA at baseline < 10 ng/ml in participants < 70 years of age, OR Gleason score =< 3+4 with a PSA at baseline =< 15 ng/ml in participants >= 70 years of age); eligible participants will be those men who are able and willing to undergo AS with PSA monitoring and a scheduled biopsy performed at the end of the study
No concurrent treatment (hormonal, radiation or systemic chemotherapy) for prostate cancer during study enrollment is planned (unless participants demonstrate clinical evidence of prostate cancer progression such as symptoms, physical exam findings, a rapidly increasing PSA, or radiologic findings which confirm disease progression)
Eastern Cooperative Oncology Group (ECOG) performance status =< 1
White blood cells (WBC) >= 3000/mm^3
Platelets >= 100,000 mm^3
Hemoglobin >= 10 g/dL
Total bilirubin =< 1.5 x upper limit of institutional normal
Alkaline phosphatase =< 1.5 x upper limit of institutional normal
Aspartate aminotransferase (AST) =< 1.5 x upper limit of institutional normal
Alanine aminotransferase (ALT) =< 1.5 x upper limit of institutional normal
Serum creatinine within 1.5 x upper limit of institutional normal
Sodium 135-144 mmol/L (inclusive)
Potassium 3.2-4.8 mmol/L (inclusive)
Participants will be required to use a medically-approved method of birth control or abstinence if their sexual partner is of child-bearing potential
Participants must be willing to forego foods, beverages and supplements containing pomegranate for the duration of the study
Ability to understand, and the willingness to sign, a written informed consent document
Exclusion Criteria:
Any prior surgery to the prostate within 30 days of baseline procedures; NOTE: Biopsies are not considered surgeries
Evidence of other cancer(s) (excluding non-melanoma skin cancer) within last 5 years
Prior pelvic radiation for any reason
Participants cannot be taking 5-alpha-reductase inhibitors while on study or within 6 months of the baseline study visit
Participants may not be taking carbamazepine (tegretol)
Participants may not be receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to PFE
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
Any significant cardiac event(s) within the 12 months prior to registration, such as episode(s) of symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris or persistent, stable angina pectoris, or cardiac arrhythmia requiring medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David F Jarrard
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lahey Hospital and Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
University of Minnesota/Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Urology San Antonio Research PA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
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Pomegranate-Extract Pill in Preventing Tumor Growth in Patients With Localized Prostate Cancer Undergoing Active Surveillance
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