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

Study Overview
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Brief Summary
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This randomized phase II trial will evaluate if a low-fat diet with fish oil has the potential to delay disease progression in patients with prostate cancer undergoing active surveillance.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine if a 1-year low-fat fish oil (omega-3 fatty acid) supplemented diet results in decreased prostate cancer Decipher score 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 20% 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.

Official Title
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A Phase II Randomized, Open-Label, Two-Arm Study of a Low-Fat Diet With Fish Oil Capsules vs. a Control Group in Men on Active Surveillance for Prostate Cancer

Conditions
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Adenocarcinoma of the Prostate, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer

Intervention / Treatment
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* Behavioral: behavioral dietary intervention
* Behavioral: behavioral dietary intervention
* Dietary Supplement: omega-3 fatty acid
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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 < 20 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm I (control)<br>Patients receive no intervention. | |
| Experimental: Arm II (fish oil)<br>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-fat diet comprising 20% Kcal from fat, 15% Kcal from protein, and 65% Kcal from carbohydrates for 1 year. Patients also receive 4 fish oil capsules per day PO for 1 year. | Behavioral: behavioral dietary intervention<br>* Receive dietary counseling<br>Behavioral: behavioral dietary intervention<br>* Receive guidelines for low-fat diet<br>Dietary Supplement: omega-3 fatty acid<br>* Given PO<br>* Other names: O3FA;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decipher score in one year prostate biopsy tissue sample | The primary statistical analysis will be to compare the Decipher score between the two intervention arms using a two-sample t-test. | 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 |