Clinical trial NCT06437574: Intensive Cholesterol-Lowering and CD8+ T Cells in Prostate Cancer
Official title: Lowering Cholesterol in Prostate Cancer to Target Rapamycin-Insensitive Companion of MTOR (TORC2) in T-Cell Surface Glycoprotein CD8 Alpha Chain (CD8+) Lymphocytes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2024-05-31
Enrollment: 140
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Pre/Post-change in percent prostate infiltrating CD8+ T lymphocytes.
timeFrame: 3 to 6 months of cholesterol-lowering intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Hyung Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: