This phase II trial studies how well simvastatin works in preventing liver cancer in patients with liver cirrhosis. Simvastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: I. To evaluate the effect of a simvastatin intervention versus placebo on the change in serum AFP-L3% from baseline to 6 months following treatment initiation in patients with liver cirrhosis who have a current model for end-stage liver disease (MELD) =\< 20. SECONDARY OBJECTIVES: I. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline on the change in: Ia. Serum AFP; Ib. Serum IL-6; Ic. Serum deoxycholic acid; Id. Liver stiffness; Ie. Fibrosis 4 index (FIB-4) score; If. MELD score. EXPLORATORY OBJECTIVES: I. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline on the change in other: Ia. serum bile acid levels; Ib. serum immune markers. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive simvastatin orally (PO) once daily (QD). Patients also undergo collection of blood on study and computed tomography (CT) scans/magnetic resonance imaging (MRI) throughout the trial. GROUP II: Patients receive placebo PO QD. Patients also undergo collection of blood on study and CT/MRI throughout the trial. In both groups, treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30, 60, and 90 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
52
Undergo collection of blood
Undergo CT
Undergo MRI
Cedars-Sinai Medical Center
Los Angeles, California, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Northwestern University
Chicago, Illinois, United States
Centro Comprensivo de Cancer de UPR
San Juan, Puerto Rico
Change in Serum AFP-L3%
Assessed by liquid-phase binding assay. Mean AFP-L3% difference calculated including all participants imputing undetectable values with 0.5%
Time frame: Baseline to 6 months
Change in Serum AFP
Assessed by liquid-phase binding assay. Mean difference in AFP, a glycoform produced by malignant liver cells.
Time frame: Baseline to 6 months
Change in Serum IL-6
Mean difference in IL-6 (interleukin-6) NPX (normalized protein expression).
Time frame: Baseline to 6 months
Change in Serum Deoxycholic Acid
Assessed by liquid chromatography coupled with mass spectrometry. Median difference in serum DCA (deoxycholic acid), a secondary bile acid.
Time frame: Baseline to 6 months
Change in Liver Stiffness
Assessed by liver elastography. Fibroscan score from a fibroscan examination (a non-invasive measurement of liver fibrosis). A test result of greater than 20kPa is generally associated with an increased HCC risk. Mean difference in liver stiffness.
Time frame: Baseline to 6 months
Change in Fibrosis 4 Index Score
The Fib-4 index is a non-invasive measure of liver stiffness. A high score (FIB4 ≥ 3.25) and low score is (FIB4 \< 1.3) The FIB-4 index is calculated as follows: FIB-4 = (Age × AST (U/L)) ÷ (PLT (109/L) × (√ ALT (U/L)). Change in mean difference.
Time frame: Baseline to 6 months
Change in Model for End-Stage Liver Disease Score
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Given PO
Ancillary studies
Given PO
University of Puerto Rico
San Juan, Puerto Rico
The Model for End-Stage Liver Disease (MELD) is a validated predictor of survival among different populations of patients with advanced liver disease. MELD = 9.57 x ln(creatinine \[mg/dL\]) + 3.78 x ln(total bilirubin \[mg/dL\]) + 11.2 x ln(INR) + 6.43. Scores range from 6 (low/ less liver disease) to 40 (high/severe liver disease). Change in mean difference.
Time frame: Baseline to 6 months