Statin Therapy Versus Placebo Prior to Prostatectomy

Overview

This is a randomized trial comparing the effect of oral simvastatin versus placebo on targets of the mevalonate pathway in men undergoing a prostatectomy as planned management for prostate cancer. Observed tissue effects will be correlated with changes in serum cholesterol and low-density lipoprotein.

Full Title of Study: “Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Screening
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: April 2013

Detailed Description

Prostate cancer patients that have chosen to undergo a prostatectomy as their primary treatment option will be recruited to this trial. Forty-four subjects will be randomized to either placebo or simvastatin (40 mg po/day) for 4 weeks prior to surgery. Serum samples will be obtained at baseline and immediately prior to prostatectomy. At prostatectomy, cancerous and benign prostate tissue will be microdissected and cryopreserved. Archival prostatectomy tissues will be used to construct tissue microarrays containing matched benign and malignant sections. The effect of HMG-CoA reductase inhibition on lipid raft cholesterol content and targets of prenylation will be determined. The incidence of apoptosis will be determined along with protein levels of mediators of apoptosis. Lastly the effect of statin therapy on cellular markers of proliferation will be determined.

Previously, we studied the effect of statin use on the risk of prostate cancer detection in a case-control study at the Portland VA Medical Center. Statin use was associated with a 62% reduction in cancer odds-risk (OR = 0.38, 95% CI 0.21-0.69). Although these epidemiologic and laboratory findings have generated enthusiasm for the study of statins in prostate cancer, no studies have examined the biologic effects of statins on prostate cancer in humans.

Hypothesis: Statin therapy prior to prostatectomy will successfully target the mevalonate pathway in the human prostate and this intervention will favorably alter tumor biomarker status.

Interventions

  • Drug: Simvastatin
    • 40 mg of simvastatin
  • Other: Placebo
    • placebo

Arms, Groups and Cohorts

  • Active Comparator: Simvastatin
    • Twenty-two men will be on the Statin arm and take 40 mg of simvastatin.
  • Placebo Comparator: Placebo
    • Twenty-two men will be on the placebo arm.

Clinical Trial Outcome Measures

Primary Measures

  • Measure the Effect of Pre-operative Simvastatin Versus Placebo on the Mevalonate Pathway Synthesis and Target Activation in Benign and Malignant Prostate Tissue.
    • Time Frame: 5 years
    • Measure the effect of pre-operative simvastatin versus placebo on the mevalonate pathway synthesis and target activation in benign and malignant prostate tissue using Androgen Receptor (AR) antibody. AR was measured in tissue obtained at the time of prostatectomy in both benign and malignant tissues.

Secondary Measures

  • Compare the Effect of Pre-operative Simvastatin Versus Placebo on Prostate Cancer Cell Apoptosis and Its Mediators in Men Undergoing Planned Prostatectomy.
    • Time Frame: 2 years
    • Compare the effect of pre-operative simvastatin versus placebo on prostate cancer cell apoptosis and its mediators in men undergoing planned prostatectomy. Apoptosis was measured by calculating the percent of Ki67 cellular staining.

Participating in This Clinical Trial

Inclusion Criteria

  • Histologically confirmed prostatic adenocarcinoma with Gleason 5 to 7 (3+4 = 7 accepted, not 4 + 3 = 7)
  • Radical prostatectomy chosen as primary treatment for prostate cancer
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria

  • Other preoperative or prior treatment directed at prostate cancer (i.e., Radiation, hormonal therapy, cryotherapy)
  • Significant active medical illness which in the opinion of the investigator would preclude protocol treatment
  • History of or active liver disease or abnormal results of the baseline liver function test (> 2 x normal)
  • Current use of:
  • simvastatin
  • lovastatin
  • other HMG-CoA inhibitors
  • lipid-lowering agents
  • Amiodarone
  • Cholestyramine
  • Cholestyramine and colestipol (bile acid sequestrants)
  • Clofibrate and fenofibrate
  • Cyclosporine
  • CYP3A4 inhibitors
  • Danazol
  • Diltiazem
  • Gemfibrozil
  • Niacin ( 1 g/day)
  • Verapamil and Warfarin
  • Known allergy or sensitivity to ingredients in simvastatin

Gender Eligibility: Male

Minimum Age: 21 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • VA Office of Research and Development
  • Collaborator
    • Oregon Health and Science University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Mark Garzotto, MD, Principal Investigator, VA Medical Center, Portland

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.