T-reg Function Changes: a Novel Immune Regulatory Effect Underlying Benefit of Statin Use on Lethal Prostate Cancer

• Status: Not yet recruiting
• Trial end date: 2025-08-01
• Target enrollment: 0
• Participant gender: Male

Summary

This study will evaluate whether simvastatin reduces intraprostatic immunosuppressive microenvironment through YAP-mediated T-reg dysfunction, and increases intraprostatic anti-tumor immune response in men recently diagnosed with localized prostate cancer electing to receive prostatectomy for their care. Half the men will be randomized to receive statins for 8 weeks prior to their surgery, while the other half will receive standard of care.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical University of South Carolina
• Treatments: Simvastatin

Criteria

Inclusion Criteria:

1. Men with pathologically-confirmed localized prostate cancer determined to be intermediate (stage T2b, or Gleason 7, or PSA 10-20 ng/mL) or high risk (stage T2c, or PSA >/=20 ng/mL, or Gleason >/=8) of biochemical recurrence at the time of biopsy

2. Electing to undergo prostatectomy;

3. Ability to provide written informed consent and willing to complete study procedures.

Exclusion Criteria:

1. Current statin use or use of non-statin lipid-lowering drug (fibrates, bile acid sequestrants, or niacin);

2. Current use of medications contraindicated for concomitant use with 40mg simvastatin:

• Gemfibrozil

• Cyclosporine

• Danazol

• CYP3A4 inhibitors: itraconazole; ketoconazole; posaconazole; erythromycin; clarithromycin; telithromycin; HIV protease inhibitors; boceprevir; telaprevir; nefazodone

3. Current use of medications requiring lower dose of simvastatin not already listed as exclusions criteria:

• Verapamil

• Diltiazem

• Amiodarone

• Ranolazine

• Calcium channel blockers: verapamil; diltiazem; amlodipine

4. Men with low-density lipoprotein cholesterol <50mg/dL

5. Statin use in the previous 12 months;

6. Discontinued statin use because of statin-related adverse event;

7. Evidence or suspicion of metastases;

8. Prior neoadjuvant or adjuvant chemotherapy, hormone therapy, or radiation therapy;

9. History of non-prostate cancer other than non-melanoma skin cancer in the last 24 months;

10. Diagnosed diabetes or currently taking diabetes medications

11. Prior myocardial infarction or stroke

12. Chronic liver disease (hepatitis or cirrhosis) or abnormal liver function (>1.5x clinical laboratory's upper limit of normal alanine aminotransferase);

13. Stage 4 or 5 chronic kidney disease (Creatinine clearance / estimated glomerular filtration rate < 30 mL/min calculated by Cockgroft-Gault formula);

14. History of myopathy or inflammatory muscle disease (>3x clinical laboratory's upper limit of normal creatine kinase).