Statin Therapy Versus Placebo Prior to Prostatectomy

• 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: VA Office of Research and Development
• Collaborator: Oregon Health and Science University
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

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

• 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

Arms and Interventions

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

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

• 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

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

• 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
• 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