Statin Therapy Versus Placebo Prior to Prostatectomy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00572468
First received: December 11, 2007
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Cancer
Prostate
Drug: Simvastatin
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Screening
Official Title: Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: December 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
Twenty-two men will be on the Statin arm and take 40 mg of simvastatin.
Drug: Simvastatin
40 mg of simvastatin
Placebo Comparator: Arm 2
Twenty-two men will be on the placebo arm.
Other: Placebo
placebo

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00572468

Locations
United States, North Carolina
Durham VA Medical Center, Durham, NC
Durham, North Carolina, United States, 27705
United States, Oregon
VA Medical Center, Portland
Portland, Oregon, United States, 97201
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Mark Garzotto, MD VA Medical Center, Portland
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00572468     History of Changes
Other Study ID Numbers: CLIN-013-07S, VA IRB#1735, SOL-07130-L
Study First Received: December 11, 2007
Last Updated: August 18, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
cancer
pre-operative surgery
prostate
prostatectomy
radiation

Additional relevant MeSH terms:
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014