Phase 0 Trial of Presurgical Cholesterol-lowering on Prostate Cancer Cell Growth
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Growth of Gleason grade 3 prostate cancer
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Biopsy containing ≥ 10 tissue cores sampled
- •Biopsy positive for adenocarcinoma of the prostate containing any quantity of Gleason 3 component (e.g. Gleason score 3+3, 3+4, 4+3)
- •Scheduled to undergo robotic radical prostatectomy
- •Serum Prostate-Specific Antigen (PSA) <20 ng/ml
- •Ability to understand and the willingness to sign a written informed consent
排除标准
- •Pharmacologic therapy (e.g. statins or ezetimibe) to lower cholesterol within 30 days prior to registration.
- •Prior treatment for CaP by surgery, irradiation, local ablative (e.g. cryosurgery or high intensity focused ultrasound) or androgen deprivation therapy.
- •5-alpha reductase inhibitors (e.g. finasteride or dutasteride) within 180 days prior to registration.
- •Hypersensitivity to simvastatin or ezetimibe.
- •Pharmacologic therapy with agents reported to produce adverse drug-drug interactions. (Table 2)
研究组 & 干预措施
Treatment
Vytorin (ezetimibe 10mg-simvastatin 40mg)
干预措施: ezetimibe 10mg-simvastatin 40mg (Drug)
结局指标
主要结局
Growth of Gleason grade 3 prostate cancer
时间窗: following 2-6 weeks of cholesterol lowering intervention.
Prostate tissue removed at the time of surgery will be examined to measure cellular growth using molecular assays.
次要结局
- Growth of benign prostate glands(following 2-6 weeks of cholesterol lowering intervention.)
- Growth of high grade prostate cancer (e.g. Gleason grade 4/5)(following 2-6 weeks of cholesterol lowering intervention.)
研究者
Hyung L. Kim, MD
Principal Investigator
Cedars-Sinai Medical Center