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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06437574
• Other study ID #: STUDY00003290
• Secondary ID: R01CA280060
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2024
• Est. completion date: May 31, 2028

Study information

• Verified date: June 2024
• Source: Cedars-Sinai Medical Center
• Contact: Amy Hoang
• Phone: 310-423-1542
• Email: Amy.Hoang[@]cshs.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: May 31, 2028
• Est. primary completion date: February 29, 2028
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 de?ned 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 a PCSK9 inhibitor

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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