Adenocarcinoma of the Prostate, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage I Prostate Cancer
Conditions
Brief summary
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.
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.
Interventions
BEHAVIORALbehavioral dietary intervention
Receive dietary counseling
DIETARY_SUPPLEMENTomega-3 fatty acid
Given PO
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Pharmavite LLC
Seafood Industry Research Fund
Jonsson Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
50 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ki-67 index | 1 year | The primary statistical analysis will be to compare the Ki67 index between the two intervention arms using a negative binomial mixed effects model |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum PSA | Up to 1 year | 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). |
| Composite measure: Long-term clinical outcomes (clinical progression, prostate cancer therapies) | Up to 15 years | 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). |
| Composite measure: Potential surrogate biomarkers of proliferation (RBC membrane fatty acid analyses, ex-vivo bioassay) | Up to 1 year | 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. |
| 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) | 1 year | 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). |
| Compliance, defined as having taken 80% or more of the daily fish oil throughout the trial determined based on pill count | Up to 1 year | Analysis of subject compliance to dietary regimen |
| Incidence of adverse events graded according to National Cancer Institute Common Toxicity Criteria version 4.0 | Up to 1 year | Measure of adverse events incidence |
| Sample storage for future research | Up to 1 year | 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. |
| Correlation of GPR120 expression in peripheral blood mononuclear cells (PBMCs) and prostate biopsy tissue with immunostaining of Ki67 and Decipher Score | Up to 1 year | 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. |
Countries
United States
Outcome results
None listed