This randomized phase II trial studies how well S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate (SAMe) works compared to a placebo in preventing liver cancer in patients with chronic hepatitis C infection. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of SAMe may keep cancer from forming in patients with advanced liver disease
PRIMARY OBJECTIVE: I. To determine whether treatment with SAMe for 24 weeks reduces serum level of alpha-fetoprotein (AFP) in patients with advanced liver disease due to chronic hepatitis C. SECONDARY OBJECTIVE: I. To determine whether treatment with SAMe for 24 weeks reduces serum levels of des-gamma carboxyprothrombin (DCP) and alpha-fetoprotein-L3 (AFP-L3) in patients with advanced liver disease due to chronic hepatitis C (hepatocellular carcinoma tumor markers). II. To determine whether treatment with SAMe for 24 weeks alters biochemical markers of liver disease (e.g., serum alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], albumin, or bilirubin, etc.) and hepatitis C viral load in patients with advanced liver disease due to chronic hepatitis C (hepatitis C liver disease). III. To determine whether treatment with SAMe for 24 weeks reduces serum levels of tumor necrosis factor-alpha (TNF-alpha), plasma levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and urine levels of F2-isoprostane in patients with advanced liver disease due to chronic hepatitis C (oxidative stress). IV. To determine whether treatment with SAMe for 24 weeks reduces plasma levels of methionine and homocysteine and increases plasma glutathione (GSH) and SAMe in patients with advanced liver disease due to chronic hepatitis C (SAMe metabolites). V. To determine the safety, tolerability and quality of life of SAMe treatment (up to 2,400 mg/day) for 24 weeks in patients with advanced liver disease due to chronic hepatitis C. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive SAMe orally (PO) twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO once daily (QD) for weeks 1-4, PO BID for weeks 5-8, and PO three times daily (TID) for weeks 9-24 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 6 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
110
University of Arizona Health Sciences Center
Tucson, Arizona, United States
Veterans Administration Long Beach Medical Center
Long Beach, California, United States
Veterans Administration Los Angeles Healthcare System
Los Angeles, California, United States
Chao Family Comprehensive Cancer Center
Orange, California, United States
Change in Serum AFP Levels
Measured using an Food and Drug Administration (FDA)-approved assay. Mean change over time for the SAMe and placebo groups will be estimated. Differences in the change over time between the treated and control groups will be tested using a two-group repeated measures analysis of variance model.
Time frame: Baseline to week 24
Treatment-related Changes in Serum DCP for Hepatocellular Carcinoma
To determine whether treatment with SAMe for 24 weeks reduces serum levels of des-gamma carboxyprothrombin (DCP) in patients with advanced liver disease due to chronic hepatitis C (hepatocellular carcinoma tumor markers).
Time frame: Baseline to week 24
Treatment-related Changes in Serum AFP-L3 (Expressed as the Percentage of Total AFTP) for Hepatocellular Carcinoma
AFP-L3 assay will be performed by Wako Laboratories using their LiBASys platform.
Time frame: Baseline to week 24
SAMe
Change in SAMe levels
Time frame: Baseline to week 24
Change in SAMe Metabolites - S-adenosylhomocysteine (SAH)
S-adenosylhomocysteine (SAH)
Time frame: Baseline to week 24
Change in SAMe Metabolites - Methionine
Methionine will be measured using HPLC with fluorescence detection.
Time frame: Baseline to week 24
Change in SAMe Metabolites - Total Homocysteine (tHcy)
Total homocysteine (tHcy)
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Correlative studies
Correlative studies
University of California At San Diego
San Diego, California, United States
Time frame: Baseline to week 24
Change in SAMe Metabolites - Plasma GSH
Plasma GSH will be measured using HPLC with fluorescence detection.
Time frame: Baseline to week 24
Change in SAMe Metabolites - Malondialdehyde (MDA)
malondialdehyde
Time frame: Baseline to week 24
Change in SAMe Metabolites - 4-hydroxynonenal (4-HNE)
Serum marker of oxidative stress. One mechanism by which SAMe is hypothesized to be beneficial is by reducing oxidative stress.
Time frame: Baseline to week 24
Change in Markers of Liver Disease - AST
AST measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays.
Time frame: Baseline to week 24
Change in Markers of Liver Disease - ALT
ALT measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays.
Time frame: Baseline to week 24
HCV RNA
Change in HCV RNA levels. Serum level of HVC RNA was measured using COBAS TaqMan HCV test (Roche Molecular Systems).
Time frame: Baseline to week 24
Changes in Quality of Life - Physical Score
Change from Baseline to Week 24 in Quality of life as as assessed with Short Form (SF)-36 Physical Component Scores. Measured quality of life using the SF-36, a widely used and general questionnaire of quality of life. Possible scores range from 0 and 100. High scores reflect good QOL and low scores reflect bad QOL. Change in QOL = (Week 24 score - Baseline score).
Time frame: Baseline to week 24
Changes in Quality of Life - Mental Score
Change from Baseline to Week 24 in Quality of life as as assessed with Short Form (SF)-36 Mental Component Scores. Measured quality of life using the SF-36, a widely used and general questionnaire of quality of life. Possible scores range from 0 and 100. High scores reflect good QOL and low scores reflect bad QOL. Change = (Week 24 score - Baseline score).
Time frame: Baseline to week 24