Statin Therapy Versus Placebo Prior to Prostatectomy

NCT ID: NCT00572468

Last Updated: 2017-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2017-04-30

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.

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.

Conditions

Cancer; Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: DOUBLE

Study Groups

Simvastatin

Twenty-two men will be on the Statin arm and take 40 mg of simvastatin.

Group Type: ACTIVE_COMPARATOR

Simvastatin

Intervention Type: DRUG

40 mg of simvastatin

Placebo

Twenty-two men will be on the placebo arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

placebo

Interventions

Simvastatin

40 mg of simvastatin

Intervention Type: DRUG

Placebo

placebo

Intervention Type: OTHER

Other Intervention Names

statin

Eligibility 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

• Minimum Eligible Age: 21 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Garzotto, MD

Role: PRINCIPAL_INVESTIGATOR

VA Medical Center, Portland

Locations

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

VA Medical Center, Portland

Portland, Oregon, United States

Countries

United States

Other Identifiers

VA IRB#1735

Identifier Type: OTHER

Identifier Source: secondary_id

SOL-07130-L

Identifier Type: OTHER

Identifier Source: secondary_id

CLIN-013-07S

Identifier Type: -

Identifier Source: org_study_id