Clinical trial NCT00458549: Polyunsaturated Fatty Acids in Treating Patients With Prostate Cancer Undergoing Prostate Biopsy and/or Surgery
Official title: Prostate Cancer Prevention by n-3 Unsaturated Fatty Acids
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Prostate Cancer
Keywords: stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-11
Enrollment: 232
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Level of eIF2α phosphorylation and Gleason score in prostate biopsy samples (Part 1)
timeFrame: 21 Days
measure: Change in phosphorylation level of eIF2α before and after n-3 polyunsaturated fatty acid supplementation (Part 2)
timeFrame: 21 Days
Secondary outcomes:
measure: Relapse-free survival (Part 2)
timeFrame: Time between surgery and the time of PSA failure 6 months and 9 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Jose A. Halperin, MD
role: PRINCIPAL_INVESTIGATOR
References: