Statin Drugs (Simvastatin and Atorvastatin) for the Treatment of Localized Prostate Cancer in Patients Undergoing Surgery
This phase II trial compares simvastatin to standard therapy for the treatment of prostate cancer that has not spread to other parts of the body (localized) in patients undergoing surgery. In addition, this clinical trial compares the effect of simvastatin to atorvastatin in treating patients with localized prostate cancer. Simvastatin is a drug that is approved by the Food and Drug Administration (FDA) to help lower cholesterol (fatty deposits in the blood) and decrease the risk of heart disease. Atorvastatin blocks an enzyme that helps make cholesterol in the body. It also causes an increase in the breakdown of cholesterol. It is a type of hydroxymethylglutaryl coenzyme A reductase inhibitor and a type of statin. This trial may help researchers determine whether or not simvastatin and atorvastatin can help to reduce the risk of prostate cancer returning after surgery.
Inclusion Criteria
- Men with pathologically-confirmed localized prostate cancer electing to undergo prostatectomy not considering radiation therapy and/or hormone therapy prior to prostatectomy
- Ability to provide written informed consent and willing to complete study procedures
- Age of at least 18 years
Exclusion Criteria
- RANDOMIZED COHORT: Use of any statin or non-statin lipid-lowering drug (fibrates, bile acid sequestrants, or niacin) in the previous 8 weeks
- RANDOMIZED COHORT: Current use of medications contraindicated for concomitant use with 40mg simvastatin: * Gemfibrozil * Cyclosporine * Danazol * CYP3A4 inhibitors: itraconazole; ketoconazole; posaconazole; erythromycin; clarithromycin; telithromycin; human immunodeficiency (HIV) protease inhibitors; boceprevir; telaprevir; nefazodone
- RANDOMIZED COHORT: 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
- RANDOMIZED COHORT: Men with low-density lipoprotein cholesterol below < 50mg/dL
- RANDOMIZED COHORT: Discontinued statin use because of statin-related adverse event
- RANDOMIZED COHORT: Evidence or suspicion of metastases
- RANDOMIZED COHORT: Prior chemotherapy, hormone therapy, or radiation therapy for prostate and non-prostate cancer
- RANDOMIZED COHORT: Use of any investigational agent within 30 days of registration
- RANDOMIZED COHORT: Diagnosed diabetes type I or II, or currently taking diabetes medications
- RANDOMIZED COHORT: Chronic liver disease (hepatitis or cirrhosis) or abnormal liver function (> 1.5 x clinical laboratory’s upper limit of normal alanine aminotransferase)
- RANDOMIZED COHORT: Stage 4 or 5 chronic kidney disease (Creatinine clearance / estimated glomerular filtration rate < 30 mL/min calculated by Cockcroft-Gault formula)
- RANDOMIZED COHORT: History of myopathy or inflammatory muscle disease (> 3 x clinical laboratory’s upper limit of normal creatine kinase)
- RANDOMIZED COHORT: Known Human immunodeficiency virus (HIV) positive, hepatitis B virus positive, or hepatitis C virus positive per medical history / records review. Testing for HIV and hepatitis is not required for the study
- OBSERVATIONAL COHORT 1 AND 2: Evidence or suspicion of metastases
- OBSERVATIONAL COHORT 1 AND 2: Prior chemotherapy, hormone therapy, or radiation therapy for prostate and non- prostate cancer
- OBSERVATIONAL COHORT 1 AND 2: Use of any investigational agent within 30 days prior to registration
- OBSERVATIONAL COHORT 1 AND 2: Diagnosed diabetes type I or II, or currently taking diabetes medications
- OBSERVATIONAL COHORT 1 AND 2: Known Human immunodeficiency virus (HIV) positive, hepatitis B virus positive, or hepatitis C virus positive per medical history / records review. Testing for HIV and hepatitis is not required for the study
Additional locations may be listed on ClinicalTrials.gov for NCT05586360.
Locations matching your search criteria
United States
Georgia
Atlanta
South Carolina
Charleston
Florence
PRIMARY OBJECTIVES:
I. To evaluate whether men diagnosed with localized prostate cancer randomized to receive a statin prior to prostatectomy have greater intraprostatic YAP-mediated regulatory T cells (T-reg) dysfunction compared to men randomized to the control group. (Randomized Cohort)
II. To evaluate whether men diagnosed with localized prostate cancer currently taking simvastatin (Observational Cohort 1) or atorvastatin (Observational Cohort 2) have greater intraprostatic YAP-mediated T-reg dysfunction compared to men randomized to the control group in the Randomized Cohort. (Observational Cohort)
SECONDARY OBJECTIVES:
I. To determine whether men randomized to the statin group have greater YAP-mediated T-reg dysfunction compared to men randomized to the control group restricting to tumor-infiltrating T-regs only. (Randomized Cohort)
II. To determine whether men randomized to the statin group have greater YAP-mediated T-reg dysfunction compared to men randomized to the control group restricting to the subset of T-regs in the adjacent normal and stromal tissue area. (Randomized Cohort)
III. To determine whether men randomized to the statin group have greater intraprostatic anti-tumor immune response compared to men randomized to the control group. (Randomized Cohort)
IV. To evaluate whether men currently taking simvastatin (Observational Cohort 1) have greater intraprostatic YAP-mediated T-reg dysfunction compared to men randomized to the simvastatin group in the Randomized Cohort. (Observational Cohort)
V. To determine whether men currently taking simvastatin (Observational Cohort 1) have greater YAP-mediated T-reg dysfunction compared to men randomized to the control group in the Randomized Cohort restricting to tumor-infiltrating T-regs only. (Observational Cohort)
VI. To determine whether men currently taking simvastatin (Observational Cohort 1) have greater YAP-mediated T-reg dysfunction compared to men randomized to the control group in the Randomized Cohort restricting to the subset of T-regs in the adjacent normal and stromal tissue area. (Observational Cohort)
VII. To determine whether men currently taking simvastatin (Observational Cohort 1) have greater intraprostatic anti-tumor immune response compared to men randomized to the control group in the Randomized Cohort. (Observational Cohort)
VIII. To determine whether men currently taking atorvastatin (Observational Cohort 2) have greater YAP-mediated T-reg dysfunction compared to men randomized to the control group in the Randomized Cohort restricting tumor-infiltrating T-regs only. (Observational Cohort)
IX. To determine whether men currently taking atorvastatin (Observational Cohort 2) have greater YAP-mediated T-reg dysfunction compared to men randomized to the control group in the Randomized Cohort restricting to the subset of T-regs in the adjacent normal and stromal tissue area. (Observational Cohort)
X. To determine whether men currently taking atorvastatin (Observational Cohort 2) have greater intraprostatic anti-tumor immune response compared to men randomized to the control group in the Randomized Cohort. (Observational Cohort)
OUTLINE:
RANDOMIZED COHORT: Patients are randomized to 1 of 2 cohorts.
ARM I (STATIN): Patients receive simvastatin orally (PO) daily for eight weeks on study prior to prostatectomy. Patients also undergo blood sample collection during screening and tissue sample collection during prostatectomy.
ARM II (CONTROL): Patients receive no intervention on study prior to prostatectomy. Patients also undergo blood sample collection during screening and tissue sample collection during prostatectomy.
OBSERVATIONAL COHORT: Patients not eligible for the randomized trial are assigned to 1 of 2 cohorts based on current statin use.
COHORT 1: Patients continue standard of care simvastatin and provide tissue from prostatectomy. Patients also undergo blood sample collection throughout the study.
COHORT 2: Patients continue standard of care atorvastatin and provide tissue from prostatectomy. Patients also undergo blood sample collection throughout the study.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMedical University of South Carolina
Principal InvestigatorMichael T. Marrone
- Primary ID18866/103472
- Secondary IDsNCI-2022-09575, Pro00120567
- ClinicalTrials.gov IDNCT05586360