Statin Therapy Versus Placebo Prior to Prostatectomy

Cancer Clinical Trial

Official title:

Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00572468
• Other study ID #: CLIN-013-07S
• Secondary ID: VA IRB#1735SOL-0
• Status: Active, not recruiting
• Phase: N/A
• First received: December 11, 2007
• Last updated: August 18, 2014
• Start date: December 2007
• Est. completion date: December 2014

Study information

• Verified date: August 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 44
• Est. completion date: December 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 21 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Screening

Related Conditions & MeSH terms

• Cancer
• Prostate

Intervention

Drug:
• Simvastatin
40 mg of simvastatin

Other:
• Placebo
placebo

Locations

Country	Name	City	State
United States	Durham VA Medical Center, Durham, NC	Durham	North Carolina
United States	VA Medical Center, Portland	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure the effect of pre-operative simvastatin versus placebo on the mevalonate pathway synthesis and target activation in benign and malignant prostate tissue.		5 years	No
Secondary	Compare the effect of pre-operative simvastatin versus placebo on prostate cancer cell apoptosis and its mediators in men undergoing planned prostatectomy.		2 years	No