RECRUITINGPhase 2INTERVENTIONAL

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

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

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Provision of signed and dated willing to sign a consent form form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. At least one Atherosclerotic Cardiovascular Disease (ASCVD) risk factor, such as: 1. ≥ 50 years of age 2. Hypertension 3. Hypercholesterolemia 4. Diabetes 5. Current or former smoker 6. First-degree family history of any cardiovascular heart disease 7. BMI \> 25 8. On hypertension treatment, statin, and/or aspirin therapy 4. Patients with clinically localized prostate cancer. That is Low or intermediate risk prostate cancer deﬁned as: 1. Pre-operative PSA (Prostate Specific Antigen) ≤ 20.0 ng/ml 2. Clinical stage T1c or cT2 3. Gleason score 3+3 or 3+4 or 4+3 5. Patients on AS with plans for surveillance biopsy 6. No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal therapy 7. Ability to take oral medication and be willing to adhere to once daily, oral Vytorin or ezetimibe. 8. Agree to avoid consumption of grapefruit and grapefruit juice ≥ one quart per day throughout study duration. Who Should NOT Join This Trial: 1. 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). 2. Current use of medications contraindicated for use with ezetimibe (i.e., gemfibrozil, cyclosporine, or danazol). 3. History of allergic or severe reaction to a either study agent. 4. History of moderate or severe myalgia with statin use. 5. Acute liver failure or decompensated cirrhosis 6. Already on maximum VYTORIN dose (10/80) 7. 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. 8. Already on a PCSK9 inhibitor Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. At least one Atherosclerotic Cardiovascular Disease (ASCVD) risk factor, such as: 1. ≥ 50 years of age 2. Hypertension 3. Hypercholesterolemia 4. Diabetes 5. Current or former smoker 6. First-degree family history of any cardiovascular heart disease 7. BMI \> 25 8. On hypertension treatment, statin, and/or aspirin therapy 4. Patients with clinically localized prostate cancer. That is Low or intermediate risk prostate cancer deﬁned as: 1. Pre-operative PSA (Prostate Specific Antigen) ≤ 20.0 ng/ml 2. Clinical stage T1c or cT2 3. Gleason score 3+3 or 3+4 or 4+3 5. Patients on AS with plans for surveillance biopsy 6. No previous treatment for prostate cancer with radiotherapy, chemotherapy, or hormonal therapy 7. Ability to take oral medication and be willing to adhere to once daily, oral Vytorin or ezetimibe. 8. Agree to avoid consumption of grapefruit and grapefruit juice ≥ one quart per day throughout study duration. Exclusion Criteria: 1. 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). 2. Current use of medications contraindicated for use with ezetimibe (i.e., gemfibrozil, cyclosporine, or danazol). 3. History of allergic or severe reaction to a either study agent. 4. History of moderate or severe myalgia with statin use. 5. Acute liver failure or decompensated cirrhosis 6. Already on maximum VYTORIN dose (10/80) 7. 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. 8. Already on a PCSK9 inhibitor

Treatments Being Tested

DRUG

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.

DRUG

Ezetimibe

Ezetimibe is a drug that targets one of the primary sources of cholesterol, absorption in the gut.

Locations (1)

Cedars-Sinai Medical Center

Los Angeles, California, United States