Lowering Cholesterol in Prostate Cancer to Target Rapamycin-Insensitive Companion Of MTOR (TORC2) in T-Cell Surface Glycoprotein CD8 Alpha Chain (CD8+) Lymphocytes
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Pre/Post-change in percent prostate infiltrating CD8+ T lymphocytes.
研究概览
简要总结
To test the hypothesis that intensive cholesterol lowering (iCL) therapy has anti-tumor immune modulating activity, the investigators will conduct an open-label, single-arm phase II trial in prostate cancer patients who are in active surveillance and undergoing a planned surveillance biopsy in 3-6 months. Eligible patients will initiate iCL with Vytorin®(group 1, 2, and 3), an FDA-approved combination of ezetimibe and simvastatin used to lower atherogenic low density lipoprotein cholesterol (LDL-C) or Ezetimibe (group 4). Starting dose will be determined by current statin use and LDL-C levels. Dose modifications of VYTORIN will be employed with the goal of achieving LDL-C <70 mg/dl. Dose adjustment is not allowed for ezetimibe.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Provision of signed and dated informed consent form.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •At least one Atherosclerotic Cardiovascular Disease (ASCVD) risk factor, such as:
- •≥ 50 years of age
- •Hypertension
- •Hypercholesterolemia
- •Current or former smoker
- •First-degree family history of any cardiovascular heart disease
- •On hypertension treatment, statin, and/or aspirin therapy
- •Patients with clinically localized prostate cancer. That is Low or intermediate risk prostate cancer defined as:
- •Pre-operative PSA (Prostate Specific Antigen) ≤ 20.0 ng/ml
- •Clinical stage T1c or cT2
- •Gleason score 3+3 or 3+4 or 4+3
- •Patients on AS with plans for surveillance biopsy
- •No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal therapy
- •Ability to take oral medication and be willing to adhere to once daily, oral Vytorin or ezetimibe.
- •Agree to avoid consumption of grapefruit and grapefruit juice ≥ one quart per day throughout study duration.
排除标准
- •Current use of medications contraindicated for use with a statin such as strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, and nefazodone).
- •Current use of medications contraindicated for use with ezetimibe (i.e., gemfibrozil, cyclosporine, or danazol).
- •History of allergic or severe reaction to a either study agent.
- •History of moderate or severe myalgia with statin use.
- •Acute liver failure or decompensated cirrhosis
- •Already on maximum VYTORIN dose (10/80)
- •Already on medication(s) known to interact with Vytorin or Ezetimibe that may prevent protocol-based escalation of cholesterol-lowering therapy from pre-enrollment baseline.
- •Already on a PCSK9 inhibitor
研究组 & 干预措施
Intensive Lipid Lowering
Single arm with dual agents (ezetimibe and simvastatin) or single agent (ezetimibe). These agents target the two primary sources of cholesterol, absorption in the gut (ezetimibe) and synthesis in the liver (simvastatin). The dual agents are available in a single pill that is FDA approved and sold under the trade name, Vytorin.
干预措施: Vytorin (Drug)
Intensive Lipid Lowering
Single arm with dual agents (ezetimibe and simvastatin) or single agent (ezetimibe). These agents target the two primary sources of cholesterol, absorption in the gut (ezetimibe) and synthesis in the liver (simvastatin). The dual agents are available in a single pill that is FDA approved and sold under the trade name, Vytorin.
干预措施: Ezetimibe (Drug)
结局指标
主要结局
Pre/Post-change in percent prostate infiltrating CD8+ T lymphocytes.
时间窗: 3 to 6 months of cholesterol-lowering intervention
Our primary hypothesis is that maximum cholesterol lowering will increase CD8+ memory T cells and increase CD8+ T cell infiltration into prostate tissue. Change in CD8+ T cells in the prostate from baseline to 3 to 6 months is the primary endpoint.
次要结局
未报告次要终点
研究者
Hyung L. Kim, MD
Principal Investigator
Cedars-Sinai Medical Center