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Statin Therapy Versus Placebo Prior to Prostatectomy

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ClinicalTrials.gov Identifier: NCT00572468
Recruitment Status : Completed
First Posted : December 13, 2007
Results First Posted : July 13, 2017
Last Update Posted : July 13, 2017
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
VA Office of Research and Development

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Cancer Prostate Cancer Drug: Simvastatin Other: Placebo Not Applicable

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.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Screening
Official Title: Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer
Study Start Date : December 2007
Actual Primary Completion Date : April 2013
Actual Study Completion Date : April 30, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Simvastatin
Twenty-two men will be on the Statin arm and take 40 mg of simvastatin.
 Drug: Simvastatin
40 mg of simvastatin
Other Name: statin
Placebo Comparator: Placebo
Twenty-two men will be on the placebo arm.
 Other: Placebo
placebo


Outcome Measures
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Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
VA Office of Research and Development
Oregon Health and Science University
Investigators
Principal Investigator: Mark Garzotto, MD VA Medical Center, Portland
More Information
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT00572468     History of Changes
Other Study ID Numbers: CLIN-013-07S
VA IRB#1735 ( Other Identifier: VA IRB )
SOL-07130-L ( Other Identifier: OHSU Knight Cancer Institute Identifier )
First Posted: December 13, 2007    Key Record Dates
Results First Posted: July 13, 2017
Last Update Posted: July 13, 2017
Last Verified: June 2017

Keywords provided by VA Office of Research and Development:
cancer
pre-operative surgery
prostate
prostatectomy
radiation

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Simvastatin
 Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors