Low-Fat Diet and Fish Oil in Men on Active Surveillance for Prostate Cancer

A Phase II Randomized, Open-Label, Two-Arm Study of a Low Omega-6, High Omega-3 Fat Diet Combined With Fish Oil vs. a Control Group in Men on Active Surveillance for Prostate Cancer

This randomized phase II trial will evaluate if a low omega-6, high omega-3 fat diet combined with fish oil has the potential to delay disease progression in patients with prostate cancer undergoing active surveillance.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage I Prostate Cancer; Adenocarcinoma of the Prostate; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Dietary supplement: omega-3 fatty acid; Behavioral: behavioral dietary intervention; Behavioral: behavioral dietary intervention

Detailed Description

PRIMARY OBJECTIVES:

I. Determine if a 1-year low omega-6, high omega-3 fat diet combined with fish oil results in decreased prostate cancer Ki-67 index as compared to a control group in men on active surveillance.

SECONDARY OBJECTIVES:

I. Evaluate the effect of a low-fat (LF)/fish oil (FO) intervention on prostate biopsy tissue markers of progression, prostate biopsy pathologic features (Gleason grade, tumor volume ), prostate-specific antigen (PSA), and long-term clinical outcomes (clinical progression, prostate cancer therapies).

II. Evaluate potential surrogate biomarkers of proliferation (red blood cell [RBC] membrane fatty acid analyses, ex-vivo bioassay).

III. Determine if a correlation exists between free fatty acid receptor 4 (GPR120) levels and progression markers in response to the LF/FO intervention.

IV. Evaluate effect of the intervention on the National Comprehension Cancer Network (NCCN) risk group V. Evaluate compliance with a 1-year + 2 year extension LF/FO intervention. VI. Evaluate safety of a 1-year + 2-year extension LF/FO intervention.

OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive no intervention.

ARM II: Patients receive dietary counseling with a research dietitian weekly for 1 month and then monthly for 11 months. Patients are given guidelines with recommended meals to follow a high omega-3, low omega-6 diet comprising 30% kilocalories (Kcal) from fat, 15% Kcal from protein, and 65% Kcal from carbohydrates for 1 year. Patients also receive 4 fish oil capsules per day orally (PO) for 1 year.

After completion of study, patients are followed up yearly for 15 years.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Jonsson Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients sign the informed consent
• Patient had a prostate biopsy performed by Dr. Mark with the Artemis device and has adenocarcinoma of the prostate
• Patient elects to undergo active surveillance
• Clinical stage T2c or less
• Gleason grade 3+4 or less
• PSA < 25
• Geographically able to have study visits at the University of California, Los Angeles (UCLA) Clinical Research Unit
• Subjects are willing to not consume lycopene, green tea or pomegranate supplements or pomegranate juice during the 1-year study
• If subjects are randomized to the control group they agree to not consume fish oil capsules during the 1-year study

Exclusion Criteria:

• Diagnostic prostate biopsy with only 1 core with cancer and < 5% of tissue from that core involved with cancer
• Patient has taken finasteride or dutasteride during the prior year
• Patient has taken fish oil during the prior 3 months
• Patient had prior treatment for prostate cancer (surgery, radiation, local ablative therapy, anti-androgen therapy or androgen deprivation therapy)
• Patient has other medical conditions that exclude him from undergoing a repeat prostate biopsy at 1-year
• Patient has allergy to fish

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Arm I (control); Patients receive no intervention.
Experimental: Arm II (fish oil); Patients receive dietary counseling with research dietitian weekly for 1 month and then monthly for 11 months. Patients are given guidelines with recommended meals to follow a low omega-6, high omega-3 fat diet combined with fish oil. Patients also receive 4 fish oil capsules per day PO for 1 year.	Other: laboratory biomarker analysis; Correlative studies; Dietary supplement: omega-3 fatty acid; Given PO; Other Names: O3FA; fish oil; n-3 fatty acid; Behavioral: behavioral dietary intervention; Receive dietary counseling; Behavioral: behavioral dietary intervention; Receive guidelines for low-fat diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ki-67 index	The primary statistical analysis will be to compare the Ki67 index between the two intervention arms using a negative binomial mixed effects model	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite measure: Prostate biopsy tissue markers of proliferation, cell cycle progression, and prostate biopsy pathologic features (Gleason grade, percent of cores with cancer, and percent of tissue with cancer)	Different types of regression models will be used to assess the influence of the intervention and clinical characteristics (ex. logistic regression, ordinal regression, Poisson regression instead of linear regression).	1 year
Serum PSA	Different types of regression models will be used to assess the influence of the intervention and clinical characteristics (ex. logistic regression, ordinal regression, Poisson regression instead of linear regression).	Up to 1 year
Composite measure: Long-term clinical outcomes (clinical progression, prostate cancer therapies)	Different types of regression models will be used to assess the influence of the intervention and clinical characteristics (ex. logistic regression, ordinal regression, Poisson regression instead of linear regression).	Up to 15 years
Composite measure: Potential surrogate biomarkers of proliferation (RBC membrane fatty acid analyses, ex-vivo bioassay)	Different types of regression models will be used to assess the influence of the intervention and clinical characteristics (ex. logistic regression, ordinal regression, Poisson regression instead of linear regression). Whether the omega-6/omega-3 ratio provides additional predictive information beyond group will be assessed by investigating whether it correlates with Ki-67 within each group.	Up to 1 year
Correlation of GPR120 expression in peripheral blood mononuclear cells (PBMCs) and prostate biopsy tissue with immunostaining of Ki67 and Decipher Score	Linear regression will be used to correlate PBMC and biopsy GPR120 gene and protein expression to 1-year Ki-67 index and Decipher score . GPR120 gene and protein expression will be added to the linear regression for Ki-67 constructed with group and clinical/demographic covariates.	Up to 1 year
Compliance, defined as having taken 80% or more of the daily fish oil throughout the trial determined based on pill count	Analysis of subject compliance to dietary regimen	Up to 1 year
Incidence of adverse events graded according to National Cancer Institute Common Toxicity Criteria version 4.0	Measure of adverse events incidence	Up to 1 year
Sample storage for future research	Urine, plasma and flash frozen prostate tissue will be stored for future research evaluating the effects of a LF/FO diet on prostate cancer progression.	Up to 1 year

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); Pharmavite LLC; Seafood Industry Research Fund
• Investigators: Principal Investigator: William Aronson, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: June 23, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimated): June 27, 2014

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 13-000432 (Other Identifier: Jonsson Comprehensive Cancer Center); P50CA092131 (U.S. NIH Grant/Contract); NCI-2014-01257 (Registry Identifier: CTRP (Clinical Trial Reporting Program))