Polyunsaturated Fatty Acids in Treating Patients With Prostate Cancer Undergoing Prostate Biopsy and/or Surgery

Prostate Cancer Prevention by n-3 Unsaturated Fatty Acids

RATIONALE: Polyunsaturated fatty acids are important for normal growth and development. One type, called omega-3 fatty acids (found in fish, fish oil, and some other foods), may affect the growth of prostate cancer.

PURPOSE: This randomized clinical trial is studying polyunsaturated fatty acids in treating patients with prostate cancer undergoing prostate biopsy and/or surgery.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Procedure: biopsy; Dietary supplement: omega-3 fatty acids

Detailed Description

OBJECTIVES:

• Compare fatty acid analysis of red blood cells, levels of eIF2α phosphorylation, and tumor differentiation grade, as measured by Gleason score, in patients undergoing prostate biopsy. (Part 1)
• Determine if neoadjuvant n-3 polyunsaturated fatty acids (PUFAs) induce phosphorylation of eIF2α in these patients. (Part 2)
• Compare eIF2α phosphorylation, Gleason score, and the time to prostate-specific antigen failure in prostate tumor samples obtained from the Gelb Center of the Dana-Farber Cancer Institute prostate tissue repository. (Part 3)

OUTLINE: This is a prospective study, followed by a randomized, double-blind, placebo-controlled study, followed by a retrospective study.

• Part 1: Patients undergo tumor biopsy and blood sample collection at baseline. Samples are analyzed by gas-liquid chromatography for determination of n-3 and n-6 polyunsaturated fatty acid (PUFA) red cell membrane concentrations. Biopsy samples are analyzed for eIF2α phosphorylation by immunohistochemistry. Some patients proceed to part 2.

• Part 2: Patients undergo blood sampling as in part 1 with additional tumor and blood collection on day 28. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral n-3 PUFAs (fish oil) once daily for 28 days prior to tumor resection.
  • Arm II (control): Patients receive oral n-6 PUFAs (corn oil) once daily for 28 days prior to tumor resection.
• Part 3: Tumor samples and associated pathology data (Gleason score) and clinical data (PSA values and patient's outcome) are obtained from a prostate tissue repository at the Gelb Center of the Dana-Farber Cancer Institute. Samples are analyzed to correlate eIF2α phosphorylation, Gleason scores, and time to PSA failure.

PROJECTED ACCRUAL: A total of 600 patients and 1,000 stored tissue samples will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 232
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men undergoing an outpatient prostate biopsy independently indicated by a physician.

• Patients will be selected from the population initially studied with a prostate biopsy for possible prostate cancer

  • sub-group without evidence of cancer
  • sub-group with advanced prostate cancer beyond the currently accepted criteria for surgical treatment,
  • sub-group with indication of radical prostatectomy
• Patients will be recruited from the population of patients from Brigham and Women's Hospital for surgery referred from other institutions/doctors where their biopsy was taken and the diagnosis of prostate cancer was originally made. These patients are not eligible for Aim 1 but will enter the randomized trial (Aim 2 with baseline)

Exclusion Criteria:

• Prostate biopsy patients who do not accept and sign an informed consent form to

  • donate ten ml of blood for fatty acid analysis in red blood cells
  • allow their prostate biopsy to be analyzed as discarded pathological material
  • authorize access to their hospital clinical information for follow up studies

• Patients with a current diagnosis of a condition that might interfere with the measurements of fatty acids in red blood cell membranes such as severe anemia (less than 9g/100m1% hemoglobin

  -- Or

• Diseases of lipid metabolism such as familial dyslipoproteinemia, liver cirrhosis, advanced renal failure, and malabsorption syndrome.
• Exclude from this study patients from (indication of radical prostatectomy) who refuse the surgical recommendation or schedule surgery at a location other than Brigham and Women's Hospital.
• Patients who are not able to complete the full program will not be taken into consideration in the final data analysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: omega-3 fatty acids; omega-3 fatty acids Oral 8g once a day for 21 days prior to (biopsy) surgery	Procedure: biopsy; Dietary supplement: omega-3 fatty acids; omega-3 fatty acids Oral 8g once a day for 21 days prior to (biopsy) surgery; Other Names: OmegaRx
Placebo Comparator: Corn Oil; Oral 8g once a day for 21 days prior to (biopsy) surgery	Procedure: biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Level of eIF2α phosphorylation and Gleason score in prostate biopsy samples (Part 1)	21 Days
Change in phosphorylation level of eIF2α before and after n-3 polyunsaturated fatty acid supplementation (Part 2)	21 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (Part 2)	detectable (> 0.1ng/m1) values following an undetectable level	Time between surgery and the time of PSA failure 6 months and 9 months

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jose A. Halperin, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2003
• Primary Completion (Actual): May 14, 2009
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: April 9, 2007
• First Submitted That Met QC Criteria: April 9, 2007
• First Posted (Estimate): April 11, 2007

Study Record Updates

• Last Update Posted (Actual): July 13, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage IV prostate cancer; stage I prostate cancer; stage II prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 03-116; P30CA006516 (U.S. NIH Grant/Contract); R01CA101034 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No