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

NCT ID: NCT06437574

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-16
• Study Completion Date: 2028-05-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Vytorin

Intervention Type: DRUG

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.

Ezetimibe

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Ezetimibe

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Hyung L. Kim, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hyung Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Amy Hoang

Role: CONTACT

Amy.Hoang@cshs.org

310-423-1542

Laura Sarmiento

Role: CONTACT

Laura.Sarmiento@cshs.org

310-423-4295

Facility Contacts

Amy Hoang

Role: primary

Amy.Hoang@cshs.org

310-423-1542

Other Identifiers

STUDY00003290

Identifier Type: -

Identifier Source: org_study_id

R01CA280060

Identifier Type: NIH

Identifier Source: secondary_id

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