Clinical trial NCT02095145: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2014-03-24
Enrollment: 38
Sex: MALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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

Primary outcomes:
measure: Change in Plasma IGF-1 From Baseline to Post-Treatment
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Compliance: Number of Participants Who Took Study Drug Per Protocol
timeFrame: Up to 1 year
measure: Incidence of Adverse Events Graded Per Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Up to 1 year
measure: Change in Plasma Biomarker Levels From Baseline: IGFBP-3
timeFrame: Week 13, Week 26, Week 39, Week 52
measure: Change in Plasma Biomarker Levels From Baseline: IGF-1/GFBP-3
timeFrame: Week 13, Week 26, Week 39, Week 52
measure: Change in Total Serum Prostate Specific Antigen (PSA) From Baseline
timeFrame: Up to 1 year
measure: Change in Serum Testosterone
timeFrame: up to 1 year
measure: Prostate Specific Antigen Doubling Time (PSA DT)
timeFrame: up to 52 Weeks
measure: Change in Tissue Biomarker Levels: PSA
timeFrame: Baseline to Week 52
measure: Change in Tissue Biomarker Levels: IGF-1
timeFrame: Baseline to Week 52
measure: Change in Tissue Biomarker Levels: IGFBP-3
timeFrame: Baseline to Week 52
measure: Change in Tissue Biomarker Levels: CASP3
timeFrame: Baseline to Week 52
measure: Change in Tissue Biomarker Levels: Ki-67
timeFrame: Baseline to Week 52
measure: Change in Tissue Biomarker Levels: IGF-Rb
timeFrame: Baseline to Week 52
measure: Change in Tissue Biomarker Levels: 8OHdG
timeFrame: Baseline to Week 52
measure: Change in Tissue Biomarker Levels: AR
timeFrame: Baseline to Week 52
measure: Change in Levels of Pomegranate Fruit Extract (PFE) Constituents/Metabolites: Urolithin A
timeFrame: Change from Baseline at Week 13, Week 26, Week 39, and Week 52
measure: Change in Levels of PFE Constituents/Metabolites: Urolithin B
timeFrame: Change from Baseline at Week 13, Week 26, Week 39, and Week 52
measure: Change in Gleason Score
timeFrame: Baseline to 1 year
measure: Change in Biopsy Tumor Involvement on Prostate Biopsy
timeFrame: Baseline to 1 year
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: San Antonio
country: United States
facility: Urology San Antonio Research PA
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: David F Jarrard
role: PRINCIPAL_INVESTIGATOR
References: