Clinical trial NCT00572468: Statin Therapy Versus Placebo Prior to Prostatectomy
Official title: Pre-Operative Statin Therapy Versus Placebo in Human Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Prostate Cancer
Keywords: cancer
pre-operative surgery
prostate
prostatectomy
radiation
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Oregon Health and Science University
First posted: 2007-12-13
Enrollment: 42
Sex: MALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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.

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

Primary outcomes:
measure: Measure the Effect of Pre-operative Simvastatin Versus Placebo on the Mevalonate Pathway Synthesis and Target Activation in Benign and Malignant Prostate Tissue.
timeFrame: 5 years
Secondary outcomes:
measure: Compare the Effect of Pre-operative Simvastatin Versus Placebo on Prostate Cancer Cell Apoptosis and Its Mediators in Men Undergoing Planned Prostatectomy.
timeFrame: 2 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Durham VA Medical Center, Durham, NC
state: North Carolina
city: Portland
country: United States
facility: VA Medical Center, Portland
state: Oregon
Study officials:
affiliation: VA Medical Center, Portland
name: Mark Garzotto, MD
role: PRINCIPAL_INVESTIGATOR
References: