Clinical trial NCT00895115: Vitamin E Supplements in Preventing Cancer in Patients at Risk of Prostate Cancer or Who Have Prostate Cancer
Official title: A Randomized Study to Investigate the Presence of Tocopherol Metabolites in the Prostate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: prostate cancer
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-08
Enrollment: 65
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: RATIONALE: Vitamin E supplements may stop or delay the development of prostate cancer in patients who are at risk of prostate cancer or who have prostate cancer. It is not yet known which vitamin E regimen is more effective in preventing prostate cancer.

PURPOSE: This randomized phase I trial is comparing vitamin E supplement regimens to see how well they work in preventing cancer in patients at risk of prostate cancer or who have prostate cancer.

Detailed description: OBJECTIVES:

* Determine the effect of tocopherol supplementation on plasma and urine levels of α-, γ-, and δ-tocopherols, PSA, and prostaglandin E_2 by comparing the blood and urine samples collected before and after the supplementation in patients with prostate cancer.
* Test the hypothesis that the supplementation reduced oxidative and nitrosative stress by measuring plasma levels of F_2-isoprostane, C-reactive protein, and 3-nitrotyrosine as well as urinary levels of 8-hydroxy-2-deoxyguanosine (8-OHdG).
* Determine the levels of α-, γ-, and δ-tocopherols in prostate tissues and analyze immunohistochemically (IHC) for cell proliferation, apoptosis, cyclooxygenase-2, 8-OHdG, and 3-nitropyrosine levels in prostate cancer/tissue slides.

OUTLINE: Patients are randomized into 1 of 3 arms.

* Arm I: Patients receive no supplementation.
* Arm II: Patients receive oral high γ-tocopherol vitamin E supplementation once daily for 1 week.
* Arm III: Patients receive oral high γ-tocopherol vitamin E supplementation once daily for 2 weeks.

Blood, urine, and tissue samples are collected periodically and analyzed for oxidative/nitrosative stress and other markers (i.e., F2-isoprostane, 8-OHdG, 3-nitrotyrosine, prostaglandin E2, C-reactive protein, and PSA), biomarkers in prostate tumors and nontumorous tissues (i.e., 8-OHdG, 3-nitrotyrosine, and cyclooxygenase-2) by IHC, and pharmacokinetics by high-performance liquid chromatography.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Meets one of the following criteria:

  * Abnormal digital rectal examination or abnormal prostate specific antigen (\> 4.0 ng/mL)
  * Obstructing prostate
  * Biopsy-proven prostate cancer
* Scheduled to undergo prostate surgery (i.e., transurethral prostatectomy or prostatectomy)

PATIENT CHARACTERISTICS:

* No uncontrolled diabetes, uncontrolled blood pressure, chronic congestive heart failure, or history of renal insufficiency
* No personal or family history of a bleeding disorder
* No known history of problems absorbing dietary fats (e.g., Crohn's disease, cystic fibrosis)

PRIOR CONCURRENT THERAPY:

* More than 2 weeks since prior NSAIDs or corticosteroids
* No concurrent supplementation of vitamin E (a multivitamin containing ≤ 60 IU of vitamin E is allowed)
* No concurrent colestipol or orlistat
* No concurrent warfarin or dicumarol

Primary outcomes:
measure: Effect of tocopherol supplementation on plasma and urine levels of α-, γ-, and δ-tocopherols, PSA, and prostaglandin E2
timeFrame: 4 years
measure: Oxidative stress and nitrosative stress as assessed by plasma levels of F2-isoprostane, C-reactive protein, and 3-nitrotyrosine as well as urinary levels of 8-hydroxy-2-deoxyguanosine (8-OHdG)
timeFrame: 4 years
measure: Levels of α-, γ-, and δ-tocopherols in prostate tissues and cell proliferation, apoptosis, cyclooxygenase-2, 8-OHdG, and 3-nitropyrosine levels as assessed by IHC
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Susan Goodin, PharmD, FCCP, BCOP
role: PRINCIPAL_INVESTIGATOR
References: