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

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ClinicalTrials.gov Identifier: NCT02095145
Recruitment Status : Active, not recruiting
First Posted : March 24, 2014
Last Update Posted : February 25, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
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 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Placebo Drug: Pomegranate-Extract Pill Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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
Actual Study Start Date : May 8, 2014
Actual Primary Completion Date : January 23, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Group I (pomegranate-extract pill)
Patients receive pomegranate-extract pill PO QD for 52 weeks (+/- 1 week).
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Drug: Pomegranate-Extract Pill
Given PO
Other Name: POMx

Placebo Comparator: Group II (placebo)
Patients receive placebo PO QD for 52 weeks (+/- 1 week).
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy




Primary Outcome Measures :
  1. Change in plasma IGF-1 [ Time Frame: Baseline to 12 months ]
    The difference between 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 :
  1. Compliance, in terms of the number of pills missed [ Time Frame: Up to 1 year ]
    Summarized by treatment arm with descriptive statistics, and tested for imbalance using Wilcoxon rank-sum test.

  2. Incidence of adverse events graded per Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 1 year ]
    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).

  3. Change in plasma biomarker levels [ Time Frame: Baseline to up to 1 year ]
    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.

  4. Total serum prostate specific antigen (PSA) [ Time Frame: Up to 1 year ]
  5. Change in tissue biomarker levels [ Time Frame: Baseline to up to 1 year ]
    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.

  6. Change in levels of PFE constituents/metabolites [ Time Frame: Baseline to up to 1 year ]
    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.

  7. Change in Gleason grade [ Time Frame: Baseline to 1 year ]
  8. Change in tumor volume on prostate biopsy [ Time Frame: Baseline to 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02095145


Locations
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United States, Alabama
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States, 35233
United States, Massachusetts
Lahey Hospital and Medical Center
Burlington, Massachusetts, United States, 01805
United States, Minnesota
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, Texas
Urology San Antonio Research PA
San Antonio, Texas, United States, 78229
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: David F Jarrard University of Wisconsin, Madison
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02095145     History of Changes
Other Study ID Numbers: NCI-2014-00695
NCI-2014-00695 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00033
CO11378 ( Other Identifier: University of Wisconsin Hospital and Clinics )
UWI2013-00-01 ( Other Identifier: DCP )
N01CN00033 ( U.S. NIH Grant/Contract )
N01CN35153 ( U.S. NIH Grant/Contract )
P30CA014520 ( U.S. NIH Grant/Contract )
First Posted: March 24, 2014    Key Record Dates
Last Update Posted: February 25, 2019
Last Verified: February 2019
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases