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Prostatic Neoplasms

Genital Neoplasms, Male

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Genital Diseases, Male

Urogenital Diseases

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Male Urogenital Diseases

Herbal and Botanical

All Drugs and Chemicals

Pomegranate

Patients receive pomegranate-extract pill PO QD for 52 weeks (+/- 1 week).

Patients receive placebo PO QD for 52 weeks (+/- 1 week).

Laboratory Biomarker Analysis

Pharmacological Study

Placebo

Pomegranate-Extract Pill

David F Jarrard

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.

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).

Pomegranate-Extract Pill in Preventing Tumor Growth in Patients With Localized Prostate Cancer Undergoing Active Surveillance

A Phase IIA Exploratory, Randomized, Placebo-Controlled Trial of Pomegranate Fruit Extract/Pomx™ in Subjects With Clinically Localized Prostate Cancer Undergoing Active Surveillance

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.

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).

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).

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.

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.

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.

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.

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 the length of biopsy cores that contained cancerous tissue from Baseline to end of study.

National Cancer Institute (NCI)

Patients receive pomegranate-extract pill PO QD for 52 weeks (+/- 1 week).

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Pomegranate-Extract Pill: Given PO

Group I (Pomegranate-extract Pill)

Patients receive placebo PO QD for 52 weeks (+/- 1 week).

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Placebo: Given PO

Group II (Placebo)

Total

Participant Age

Age, Customized

The final report for this study contains data for participant 'gender', the study team would like to note this for consistency.

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) 0 = Fully active, able to carry on all pre-disease performance without restriction

1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

ECOG Performance Status

Systolic Blood Pressure

Diastolic Blood Pressure

Temperature

Pulse

Height

Weight

Body Mass Index

Skin

Prostate

Head/Eyes/Ears/Neck/Throat

Neurological

Abdomen

Genitalia

History or Baseline Presence of Disease / Abnormality

3+3=6

3+4=7

Gleason Score

David Jarrard

Change in Plasma IGF-1 From Baseline to Post-Treatment

Week 13

Week 26

Week 39

End of Study (Week 52)

One participant has no compliance values for weeks 26 and 39.

Compliance: Number of Participants Who Took Study Drug Per Protocol

Any Adverse Event

Multiple Adverse Events

Grade 3 (Severe) or Worse

Serious Adverse Events

Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE)

Change Baseline to Week 13

Change Baseline to Week 26

Change Baseline to Week 39

Change Baseline to Week 52

Change in Plasma Biomarker Levels From Baseline: IGFBP-3

Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3

Change from Baseline Week 26

Change from Baseline Week 39

Statistician notes that serum PSA data is missing for one participant in the pomegranate extract arm for all time points, missing for another in the pomegranate arm at week 39, and one from the placebo arm at week 39.

Change in Total Serum Prostate Specific Antigen (PSA) From Baseline

comparison of both arms at end of study, week 52

Baseline

Week 52

Patients receive pomegranate-extract pill orally once a day for 52 weeks (+/- 1 week).

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Pomegranate-Extract Pill: Given PO

Patients receive placebo orally once a day for 52 weeks (+/- 1 week).

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Placebo: Given PO

Change in Serum Testosterone

One of the participant's PSA values were 'non-detectable', therefore PSA observations could not be calculated for that participant.

Prostate Specific Antigen Doubling Time (PSA DT)

Change From Baseline: Benign

Change From Baseline: Adjacent

Change From Baseline: Tumor

The number analyzed depends on the identification and recovery of relevant tissue type (benign, adjacent, tumor).

Change in Tissue Biomarker Levels: PSA

Change from Baseline: IGF-1 Adjacent (Nuc)

Change from Baseline: IGF-1 Adjacent (Cyt)

Change from Baseline: IGF-1 Benign (Cell)

Change from Baseline: IGF-1 Adjacent (Cell)

Change From Baseline: Nuc Benign

Change From Baseline: Nuc Adjacent

Change From Baseline: Nuc Tumor

Change From Baseline: Cyt Benign

Change From Baseline: Cyt Adjacent

Change From Baseline: Cyt Tumor

Change From Baseline: Cell Benign

Change From Baseline: Cell Adjacent

Change From Baseline: Cell Tumor

Change in Tissue Biomarker Levels: IGF-1

Change From Baseline: Nuc Adjacent p-value

Change From Baseline: Cyt Adjacent p-value

Change From Baseline: Cell Benign p-value

Change From Baseline: Cell Adjacent p-value

Change in Tissue Biomarker Levels: IGFBP-3

Change in Tissue Biomarker Levels: CASP3

Change From Baseline:Tumor

Change in Tissue Biomarker Levels: Ki-67

Change from Baseline: Nuc Adjacent p-value

Change from Baseline: Cyt Adjacent p-value

Change from Baseline: Cell Benign p-value

Change from Baseline: Cell Adjacent p-value

Change in Tissue Biomarker Levels: IGF-Rb

Change in Tissue Biomarker Levels: 8OHdG

Change in Tissue Biomarker Levels: AR

Change from Baseline Week 13

Change from Baseline Week 52

Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A

Change in Levels of PFE Constituents/Metabolites: Urolithin B

Surgery Visit (52 Weeks)

Change in Gleason Score

Change in Tumor Volume from baseline to end of study per arm

One participant has a baseline measurement but does not have an end of study measurement, a change in the biopsy tumor involvement for this participant is therefore not possible to calculate.

Spots Global Cancer Trial Database for psa level less than ten