Prostate Cancer
Conditions
Brief summary
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.
Interventions
DRUGVytorin
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.
DRUGEzetimibe
Ezetimibe is a drug that targets one of the primary sources of cholesterol, absorption in the gut.
Sponsors
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre/Post-change in percent prostate infiltrating CD8+ T lymphocytes. | 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. |
Countries
United States
Contacts
CONTACTAmy Hoang
CONTACTLaura Sarmiento
PRINCIPAL_INVESTIGATORHyung Kim, MD
Cedars-Sinai Medical Center
Outcome results
None listed