Intensive Cholesterol-Lowering and CD8+ T Cells in Prostate Cancer

Официальное название

Lowering Cholesterol in Prostate Cancer to Target Rapamycin-Insensitive Companion Of MTOR (TORC2) in T-Cell Surface Glycoprotein CD8 Alpha Chain (CD8+) Lymphocytes

Обзор

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.

Вмешательства

• Препарат Vytorin
  Vytorin is a drug combination (Ezetimibe and Simvastatin) that targets the two primary sources of cholesterol, absorption in the gut and synthesis in the liver.
• Препарат Ezetimibe
  Ezetimibe is a drug that targets one of the primary sources of cholesterol, absorption in the gut.

Первичные конечные точки

• Pre/Post-change in percent prostate infiltrating CD8+ T lymphocytes. [Срок оценки: 3 to 6 months of cholesterol-lowering intervention]

Критерии участия

Критерии включения

• 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
• Diabetes
• Current or former smoker
• First-degree family history of any cardiovascular heart disease
• BMI > 25
• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Cedars-Sinai Medical Center — Los Angeles

Идентификаторы

NCT: NCT06437574 · STUDY00003290 · R01CA280060

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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