Statin Therapy Versus Placebo Prior to Prostatectomy

Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Prostate Cancer
• Intervention / Treatment: Other: Placebo; Drug: Simvastatin

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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center, Durham, NC
  • Oregon
    • Portland, Oregon, United States, 97201
      • VA Medical Center, Portland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: statin
Placebo Comparator: Placebo; Twenty-two men will be on the placebo arm.	Other: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure the Effect of Pre-operative Simvastatin Versus Placebo on the Mevalonate Pathway Synthesis and Target Activation in Benign and Malignant Prostate Tissue.	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.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the Effect of Pre-operative Simvastatin Versus Placebo on Prostate Cancer Cell Apoptosis and Its Mediators in Men Undergoing Planned Prostatectomy.	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.	2 years

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Oregon Health and Science University
• Investigators: Principal Investigator: Mark Garzotto, MD, VA Medical Center, Portland

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 30, 2017

Study Registration Dates

• First Submitted: December 11, 2007
• First Submitted That Met QC Criteria: December 11, 2007
• First Posted (Estimate): December 13, 2007

Study Record Updates

• Last Update Posted (Actual): July 13, 2017
• Last Update Submitted That Met QC Criteria: June 13, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: cancer; radiation; prostate; prostatectomy; pre-operative surgery
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: CLIN-013-07S; VA IRB#1735 (Other Identifier: VA IRB); SOL-07130-L (Other Identifier: OHSU Knight Cancer Institute Identifier)