T-reg Function Changes: a Novel Immune Regulatory Effect Underlying Benefit of Statin Use on Lethal Prostate Cancer
About this study
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.
- Condition
- Prostate Cancer
- Tested
- Simvastatin 40mg
- Sponsor
- Medical University of South Carolina
Who can join
- Age
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
Inclusion 6
- Minimum age: 18 years
- Eligible sex: Male
- Study condition: Prostate Cancer
- 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
- Electing to undergo prostatectomy;
- Ability to provide written informed consent and willing to complete study procedures.
Exclusion 23
- Current statin use or use of non-statin lipid-lowering drug (fibrates, bile acid sequestrants, or niacin);
- 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
- 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
- Men with low-density lipoprotein cholesterol \<50mg/dL
- Statin use in the previous 12 months;
- Discontinued statin use because of statin-related adverse event;
- Evidence or suspicion of metastases;
- Prior neoadjuvant or adjuvant chemotherapy, hormone therapy, or radiation therapy;
- History of non-prostate cancer other than non-melanoma skin cancer in the last 24 months;
- Diagnosed diabetes or currently taking diabetes medications
- Prior myocardial infarction or stroke
- Chronic liver disease (hepatitis or cirrhosis) or abnormal liver function (\>1.5x clinical laboratory's upper limit of normal alanine aminotransferase);
- Stage 4 or 5 chronic kidney disease (Creatinine clearance / estimated glomerular filtration rate \< 30 mL/min calculated by Cockgroft-Gault formula);
- History of myopathy or inflammatory muscle disease (\>3x clinical laboratory's upper limit of normal creatine kinase).
Where
2 sites, 2 recruiting
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States
Emory University
Atlanta, Georgia, United States
Contact
-
Alan Brisendine
843-792-9007 brisend@musc.edu
-
Jasmin M Brooks
8439067139 brooksjm@musc.edu
Potential match only. Final eligibility is determined by the study team.