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

NCT06437574 — Phase 2, Recruiting, 140 participants, Cedars-Sinai Medical Center

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

Lowering Cholesterol in Prostate Cancer to Target Rapamycin-Insensitive Companion Of MTOR (TORC2) in T-Cell Surface Glycoprotein CD8 Alpha Chain (CD8+) Lymphocytes

Registry	NCT06437574
Status	Recruiting
Phase	Phase 2
Study type	Interventional; na, single group, masking: none, prevention
Enrollment	140 (Estimated)
Sponsor	Cedars-Sinai Medical Center (Other)
Conditions	Prostate Cancer
Interventions	Vytorin, Ezetimibe (Drug)
Dates	start 2024-07-16, primary completion 2028-02-29 (estimated), completion 2028-05-31 (estimated), first posted 2024-05-31, last updated 2026-03-11
Locations	1 site in United States

-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.

Expand all sections · Collapse all

+Arms and interventions

Arm	Type	Interventions	Description
Intensive Lipid Lowering	Experimental	Drug: Vytorin; Drug: 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.

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

+Outcome measures

Primary outcomes

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.

+Eligibility

Sex: Male, ages: 18 Years to any

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

+Locations (1)

Facility	City	Country	Status
Cedars-Sinai Medical Center	Los Angeles, California	United States	Recruiting

+Investigators

Hyung Kim, MD, Principal investigator, Cedars-Sinai Medical Center

+Funding

NIH grants: R01CA280060