The following datasets contain the data available for EPPT UWI2013-00-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Raw Datasets

These 39 datasets contain the raw form data received, excluding PII.

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Trial Summary

Lay Summary

This randomized phase II trial studied pomegranate-extract pill in patients with prostate cancer limited to the prostate gland (localized), who have chosen observation as their treatment plan. In this study, researchers wanted to find out if there is a difference in the level of multiple important blood and tissue markers, and to assess toxicity and compliance between people taking a placebo (“sugar pill”) versus those taking POMx™.

Scientific Summary

This is a randomized phase II study of oral Pomegranate Fruit Extract/POMx™ versus oral placebo in men with prostate cancer who are on active surveillance. The goal of the study is to characterize the effects of POMx™ on insulin-like growth factor (primary endpoint) and multiple additional plasma and tissue markers, and to assess toxicity and participant compliance.

Patients are randomized to 1 of 2 treatment arms:

• Arms
  • ARM I: Pomegranate-extract pill PO QD for 52 weeks (+/- 1 week)
  • ARM II: Placebo PO QD for 52 weeks (+/- 1 week)

Enrollment Statistics

Target Enrollment: 30

Actual Registration: 38

• 30 people randomized (30 of 38 registered)
  • 15 in Arm I (15 out of 30 randomized): Pomegranate Extract 1000 mg
    • 14 completed the study.
    • 1 participant withdrew due to protocol non-compliance (i.e., pomegranate consumption while on study).
  • 15 in Arm II (15 out of 30 randomized): Placebo
    • 15 completed the study.
• 8 people were not randomized (8 of 38 registered)
  • 5 participants’ PSA levels exceeded the upper limit.
  • 2 participants’ potassium level exceeded the upper limit.
  • 1 participant experienced a recent onset of cardiac arrhythmia.

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 <10ng/ml in participants <70 years of age, OR Gleason Score ≤3+4 with a PSA at baseline ≤15ng/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).
• Age ≥21 years. Because no dosing or adverse event data are currently available on the use of POMx™ in participants <21 years of age, children are excluded from this study.
• ECOG performance status ≤1.
• Participants must have normal organ and marrow function as defined below:
  • Hematologic:
    • WBC ≥ 3000/mm3
    • platelets ≥ 100,000mm3
    • hemoglobin ≥10 g/dL
  • Hepatic:
    • Total bilirubin ≤ 1.5 x upper limit of institutional normal
    • alkaline phosphatase ≤ 1.5 x upper limit of institutional normal
    • AST ≤1.5 x upper limit of institutional normal
    • ALT ≤1.5 x upper limit of institutional normal
  • Renal:
    • Serum creatinine within 1.5 x upper limit of institutional normal
  • Electrolytes:
    • Sodium 135-144 mmol/L (inclusive)
    • Potassium 3.2-4.8 mmol/L (inclusive)
• The effects of PFE on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, 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-α-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.

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Over the course of this study 2,929 biospecimens were collected. Blood and urine were collected at baseline for pharmacokinetic analyses, plasma biomarker analyses, total serum PSA and testosterone levels. Pharmacokinetic analyses, plasma biomarker analyses, and total serum PSA were done on all subsequent visits while serum testosterone levels were only done on weeks 26 and 52. Prostate biopsy tissue was taken at baseline and on week 52.

One urine collection cup was used to ideally capture at least 10 ml of urine. The collected urine was then aliquoted into 4 cryovials. If the participant did not void at least 10 ml then as many cryovials were filled as were needed. The tubes were labeled and then frozen at -70°C until study completion.

Blood specimens were collected with a provided 3P lab kit that contained green top tubes, red top tubes, and cryovials. For each of the green top tubes, 9 ml of blood was drawn and for the red top tubes 2.5 ml of blood. Green top tubes were centrifuged at ~1000xG for 10-15 minutes and the plasma was aliquoted into 8 cryovials. The red top tubes were allowed to clot and then centrifuged at ~1000xG for 10-15 minutes as well. Each kit could have up to 2 red top tubes and each tube was aliquoted equally into 2 cryovials resulting in a total of 2 or 4 cryovials of serum. The tubes were labeled and then frozen at -70°C until study completion.

Tissue samples will be taken from the prostate biopsy paraffin-embedded tissue blocks. These blocks will be requested to contain an adenocarcinoma. From these tissue blocks, 10 unstained slides may be substituted. Each slide should be cut in 4-5 μm thick sections and picked up on Super Frost Plus or other comparably charged slides. These slides should not be pre-melted or baked.

*Either 1 or 2 red top tubes were collected and was processed into either 2 or 4 cryovials.

Results/Findings:

PFE administration for 12-month was well-tolerated and the protocol followed in an active surveillance population. Analyses suggest that PFE contains bioactive compounds capable of altering biomarkers involving oxidative stress and androgen signaling in prostate tumor and normal-appearing adjacent tissue. No alterations in the IGF axis were noted. This finding of study adherence and target activity provides a rationale for the further investigation of PFE in the active surveillance population.