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

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.

Eligibility

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).

Conditions2

Locations2 sites

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