There is evidence in human studies as well as animal studies that treatments to lower
cholesterol can reduce the risk of dying from prostate cancer.To decide if
cholesterol-lowering therapy can slow the growth of prostate cancer, the investigators
would like to lower cholesterol prior to surgery and then measure the growth of prostate
cancers cells when the prostate has been removed. The investigators will use the
combination of two drugs that is approved by the U.S. Food and Drug Administration to
lower cholesterol. The drug combination is commercially available with a doctor's
prescription and sold as Vytorin®. It is known that maximal cholesterol-lower effects are
seen after 2 weeks of treatment with Vytorin®. Therefore, study patients receive at least
2 weeks, but no more than 6 weeks of Vytorin® prior to surgery.
Additional locations may be listed on ClinicalTrials.gov for NCT02534376.
See trial information on ClinicalTrials.gov for a list of participating sites.
BACKGROUND AND RATIONALE
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of
cancer death among men in North America. In the US, there are more than 200,000 newly
diagnosed cases and nearly 40,000 deaths from prostate cancer (CaP) annually. Although
elevated lipid levels are understood to increase risk of coronary heart disease, their
importance for CaP is not understood. Epidemiologic studies consistently show an
association between lipid lowering interventions and decreased risk of advanced CaP.
There are no reports of prospective studies of lipid-lowering interventions directed at
CaP.
Epidemiologic studies and preclinical observations suggest that interventions to lower
cholesterol will decrease the risk of developing lethal CaP. However, a definitive, phase
III study of cholesterol-lowering effects on advanced CaP development is needed prior to
clinical implementation of this intervention. Such a trial will require a massive
commitment of resources for the large number of patients needing long follow-up. A
rational intermediate step is to conduct a presurgical intervention study to lower
cholesterol in men undergoing radical prostatectomy. Molecular evidence of treatment
effect will provide a sound rationale for definitive clinical trials, and may provide
predictive biomarkers that can be validated in these future trials.
The investigators propose a prospective trial to assess the effects on the human prostate
of a maximal cholesterol lowering strategy using dual agents in men already scheduled to
undergo radical prostatectomy for prostate cancer.
Simvastatin is a cholesterol-lowering drug approved by the FDA in 1991 and is now
commercially available as Zocor (Merck) or as a generic agent. After ingestion, it is
converted from an inactive lactone to the corresponding β-hydroxyacid, which inhibits
HMG-CoA reductase and the conversion of HMG-CoA to mevalonate. Ezetimibe is a
cholesterol-lowering agent that operates by a distinct mechanism from HMG-CoA reductase
inhibitors. It was FDA approved in 2002 and is commonly administered alone or in
combination with a statin. It specifically inhibits a cholesterol transporter in the
small intestines and selectively inhibits the absorption of cholesterol and related
sterols.
A single pill that combines simvastatin and ezetimibe is available from Merck (Vytorin).
This commercially available agent at its standard dose is used in this trial. This study
uses the combination of simvastatin and ezetimibe to achieve maximal cholesterol lowering
prior to prostatectomy.
Trial PhasePhase O
Trial Typesupportive care
Lead OrganizationCedars Sinai Medical Center
