Precancerous Condition, Prostate Cancer
Conditions
Keywords
prostate cancer, precancerous condition
Brief summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of fish oil and/or green tea may prevent prostate cancer. PURPOSE: This randomized clinical trial is studying how well a fish oil and/or green tea supplement works in preventing prostate cancer in patients with prostatic intraepithelial neoplasia or who are at risk for developing prostate cancer.
Detailed description
OBJECTIVES: * Determine the cancer preventing effects of fish oil supplementation and green tea extract use on markers of alteration in lipid metabolism in prostate tissue samples. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to age (under 65 vs 65 and over). Patients are randomized to 1 of 4 treatment arms. * Arm I: Patients receive oral fish oil three times daily and oral green tea extract twice daily. * Arm II: Patients receive an oil placebo three times daily and oral green tea extract twice daily. * Arm III: Patients receive oral fish oil three times daily and a placebo twice daily. * Arm IV: Patients receive an oil placebo three times daily and another placebo twice daily. Treatment in one of the above-listed arms continues for up to 20 weeks in the absence of disease progression or unacceptable toxicity. All patients undergo a prostate biopsy on the last day of study treatment. After completion of study treatment, patients receive a follow-up phone call at/around 30 days later. PROJECTED ACCRUAL: A total of 144 patients will be accrued for this study.
Interventions
DIETARY_SUPPLEMENTgreen tea catechin extract
Given orally 2 times/day
DIETARY_SUPPLEMENTfish oil
Given orally 3 times/day
OTHERplacebo
Given olive oil placebo orally 3 times/day
Sponsors
United States Department of Defense
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
21 Years to 120 Years
Healthy volunteers
Yes
Inclusion criteria
* Clinician recommends repeat biopsy of the prostate (Repeat is defined as any recommended biopsy of the prostate subsequent to an earlier biopsy of the prostate)
Exclusion criteria
* Definitive invasive prostate cancer on initial biopsy * Significant active medical illness that in the opinion of the clinician would preclude protocol treatment. * History of ventricular tachycardia or ventricular fibrillation * Subject reported use of fish oil (greater than 1 gram per day) or green tea supplement within 30 days before Day 1 of study treatment * Subject reported use of fish oil ≤ 1 gram per day and unwilling to discontinue use for the duration of the trial * Use of warfarin or need for therapeutic anticoagulation at time of biopsy or at anytime during the course of the trial. * Subject reported allergy or sensitivity to fish oil, olive oil or green tea * Subject reported history of hemophilia, van Willebrands disease or other bleeding disorder, except when the subject is evaluated by a hematologist who determines that fish oil supplementation is not contraindicated. * Total bilirubin greater than institutional upper limit of normal * Concurrent high risk study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | Baseline (pre-intervention) and end of study (time to surgery for those with malignant findings or up to 8 weeks for those with benign biopsies, post-intervention) | Sections of paraffin-embedded prostate biopsy tissue were stained for fatty acid synthase (FAS) expression. The FAS Summary Score was calculated as the product of percent stained (1=0-25%, 2=25-50%, 3=51-75%, 4=76-100%) and stain intensity (0-3) by immunohistochemistry. The range of the product is 0-300. |
| Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention | End of study | Cell Proliferation by Ki67 is calculated as the percent stained by immunohistochemistry. Ki-67 values were log-transformed because the original distribution was skewed. Analysis was done on log-base2 transformed values. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Fish Oil, Green Tea Catechin Extract) Patients receive oral fish oil 3/day and oral green tea extract 2/day
green tea catechin extract: Given orally 2 times/day
fish oil: Given orally 3 times/day | 14 |
| Arm II (Fish Oil Placebo, Green Tea Catechin Extract) Patients receive an oil placebo 3/day and oral green tea extract 2/day
green tea catechin extract: Given orally 2 times/day
placebo: Given olive oil placebo orally 3 times/day | 15 |
| Arm III (Fish Oil, Green Tea Placebo) Patients receive oral fish oil 3/day and a placebo mimicking green tea catechins 2/day
fish oil: Given orally 3 times/day
placebo: Given green tea placebo orally 2 times/day | 28 |
| Arm IV (Fish Oil Placebo, Green Tea Placebo) Patients receive an oil placebo mimicking fish oil 3/day and another placebo mimicking green tea catechins 2/day
placebo: Given olive oil placebo orally 3 times/day
placebo: Given green tea placebo orally 2 times/day | 28 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Non-Compliance | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Arm I (Fish Oil, Green Tea Catechin Extract) | Arm II (Fish Oil Placebo, Green Tea Catechin Extract) | Arm III (Fish Oil, Green Tea Placebo) | Arm IV (Fish Oil Placebo, Green Tea Placebo) |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 6 Participants | 5 Participants | 10 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 8 Participants | 10 Participants | 18 Participants | 19 Participants |
| Diagnosis Benign | 57 participants | 9 participants | 11 participants | 16 participants | 21 participants |
| Diagnosis Prostate Cancer | 15 participants | 2 participants | 1 participants | 6 participants | 6 participants |
| Diagnosis Prostatic Intraepithelial Neoplasia (PIN) | 13 participants | 3 participants | 3 participants | 6 participants | 1 participants |
| Region of Enrollment United States | 85 participants | 14 participants | 15 participants | 28 participants | 28 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 85 Participants | 14 Participants | 15 Participants | 28 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 14 | 2 / 15 | 5 / 29 | 1 / 31 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 | 0 / 29 | 0 / 31 |
Outcome results
Primary
Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention
Cell Proliferation by Ki67 is calculated as the percent stained by immunohistochemistry. Ki-67 values were log-transformed because the original distribution was skewed. Analysis was done on log-base2 transformed values.
Time frame: End of study
Population: Number of participants for recruitment was based on power calculations. All participants consented and randomized were included in analyses. Analysis was intention to treat. No imputations for missing data were conducted.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I | Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention | 18.5 %age of cells & nuclei stained |
| Arm II | Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention | 8 %age of cells & nuclei stained |
| Arm III | Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention | 10 %age of cells & nuclei stained |
| Arm IV | Cell Proliferation by Ki67-immunohistochemistry at Pre- and Post-intervention | 12 %age of cells & nuclei stained |
Comparison: Mixed effects model to assess the effect of time (pre vs. post) and treatment (GTFO, GT, FO and Placebo) on Ki-67p-value: 0.1573Mixed Models Analysis
Primary
Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score)
Sections of paraffin-embedded prostate biopsy tissue were stained for fatty acid synthase (FAS) expression. The FAS Summary Score was calculated as the product of percent stained (1=0-25%, 2=25-50%, 3=51-75%, 4=76-100%) and stain intensity (0-3) by immunohistochemistry. The range of the product is 0-300.
Time frame: Baseline (pre-intervention) and end of study (time to surgery for those with malignant findings or up to 8 weeks for those with benign biopsies, post-intervention)
Population: Number of participants for recruitment was based on power calculations. All participants consented and randomized were included in analyses. Analysis was intention to treat. No imputations for missing data were conducted.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | PRE data | 147 units on a scale | Standard Deviation 98.6 |
| Arm I | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | POST data | 140.7 units on a scale | Standard Deviation 100.3 |
| Arm II | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | POST data | 159.3 units on a scale | Standard Deviation 75.5 |
| Arm II | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | PRE data | 158.8 units on a scale | Standard Deviation 84.6 |
| Arm III | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | POST data | 145.2 units on a scale | Standard Deviation 72.2 |
| Arm III | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | PRE data | 138.3 units on a scale | Standard Deviation 63.8 |
| Arm IV | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | PRE data | 102.3 units on a scale | Standard Deviation 85.9 |
| Arm IV | Fatty Acid Synthase Expression by Immunohistochemistry at Pre- and Post-intervention (FAS Summary Score) | POST data | 152.2 units on a scale | Standard Deviation 80.9 |
Comparison: Mixed effects model to assess the effect time (pre vs. post) and treatment (GTFO, GT, FO and Placebo) on FAS summary scoresp-value: 0.1521Mixed Models Analysis