Statin Therapy Versus Placebo Prior to Prostatectomy - Full Text View

Purpose

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	Intervention
Cancer Prostate Cancer	Drug: Simvastatin Other: Placebo


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Investigator Primary Purpose: Screening
Official Title:	Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: prostate cancer

MedlinePlus related topics: Prostate Cancer Statins

Drug Information available for: Simvastatin

U.S. FDA Resources

Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:

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:

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.


Enrollment:	42
Study Start Date:	December 2007
Study Completion Date:	April 30, 2017
Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	21 Years and older (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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


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 )
Study First Received:	December 11, 2007
Results First Received:	April 17, 2017
Last Updated:	June 13, 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

ClinicalTrials.gov processed this record on July 21, 2017