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

NCT06437574 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00003290R01CA280060
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Intensive Lipid Lowering

EXPERIMENTAL

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; Drug: Ezetimibe

Interventions

Vytorin 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.

Intensive Lipid Lowering

Ezetimibe DRUG

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

Intensive Lipid Lowering

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• At least one Atherosclerotic Cardiovascular Disease (ASCVD) risk factor, such as:
• ≥ 50 years of age
• Hypertension
• Hypercholesterolemia
• Diabetes
• Current or former smoker
• First-degree family history of any cardiovascular heart disease
• BMI \> 25
• On hypertension treatment, statin, and/or aspirin therapy
• Patients with clinically localized prostate cancer. That is Low or intermediate risk prostate cancer defined as:
• Pre-operative PSA (Prostate Specific Antigen) ≤ 20.0 ng/ml
• Clinical stage T1c or cT2
• Gleason score 3+3 or 3+4 or 4+3

You may not qualify if:

• 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).
• Current use of medications contraindicated for use with ezetimibe (i.e., gemfibrozil, cyclosporine, or danazol).
• History of allergic or severe reaction to a either study agent.
• History of moderate or severe myalgia with statin use.
• Acute liver failure or decompensated cirrhosis
• Already on maximum VYTORIN dose (10/80)
• 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.
• Already on a PCSK9 inhibitor

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ezetimibe, Simvastatin Drug Combination; Ezetimibe

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Simvastatin; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Hyung Kim, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Hoang

CONTACT

310-423-1542; Amy.Hoang@cshs.org

Laura Sarmiento

CONTACT

310-423-4295; Laura.Sarmiento@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: May 31, 2024
• Study Start: July 16, 2024
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)