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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Vytorin; Drug: Ezetimibe

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laura Sarmiento; Phone Number: 310-423-4295; Email: Laura.Sarmiento@cshs.org
• Study Contact Backup: Name: Amy Hoang; Phone Number: 310-423-1542; Email: Amy.Hoang@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Amy Hoang; Phone Number: 310-423-1542; Email: Amy.Hoang@cshs.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre/Post-change in percent prostate infiltrating CD8+ T lymphocytes.	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.	3 to 6 months of cholesterol-lowering intervention

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Hyung Kim, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: May 29, 2024
• First Posted (Actual): May 31, 2024

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Drug Combinations; Azetidines; Azetines; Lovastatin; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
• Other Study ID Numbers: STUDY00003290; R01CA280060 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes