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

Phase 2

Recruiting

• Conditions: Prostate Cancer
• Interventions: Drug: Vytorin; Drug: Ezetimibe

• Registration Number: NCT06437574
• Lead Sponsor: Cedars-Sinai Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-23
• Study First Submitted QC: 2024-05-29
• Study First Posted: 2024-05-31
• Status Verified: 2024-07
• Study Start: 2024-07-16
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-27
• Primary Completion: 2028-02-29
• Study Completion: 2028-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 140

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intensive Lipid Lowering	Vytorin	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.
Intensive Lipid Lowering	Ezetimibe	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.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States