Liver Cancer Prevention Trial in Patients With Chronic Hep C Infection
Condition: Adult Primary Liver Cancer; Hepatitis C Infection
MeSH terms: Infections; Hepatitis C; Liver Neoplasms; Hepatitis
Intervention: S-adenosyl-L-methionine disulfate p-toluene-sulfonate; placebo; laboratory biomarker analysis; immunoenzyme technique; high performance liquid chromatography
Intervention description: Given PO; Given PO; Correlative studies; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chronic hepatitis C infection diagnosed by presence of hepatitis C ribonucleic acid
             (RNA) in serum by test of hepatitis C virus (HCV) RNA

          -  No significant alcohol use (7 or fewer drinks per week) for the past 12 months

          -  Serum AFP (at screening) between 15 and 100 ng/mL (15 ng/mL =< AFP =< 100 ng/mL) as
             measured by the Bayer Advai Centaur chemiluminescence system OR Serum AFP between 10
             and 100 ng/mL (10 ng/mL =< AFP =<100 ng/mL) as measured by Diagnostic Products
             Corporation Immulite assay system OR AFP between 12 and 100 ng/mL (12 ng/mL =< AFP =<
             100 ng/mL) as measured by Ortho ECiQ assay system

          -  Evidence of advanced liver disease based on one or more of the following:

          -  Platelet count less than 150,000/mm^3

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio > 0.75

          -  Liver biopsy demonstrating bridging fibrosis or cirrhosis

          -  No treatment with interferon (recombinant interferon alfa), peginterferon
             (PEG-interferon alfa-2b), or ribavirin for at least 4 months, and not anticipated to
             start specific treatment for hepatitis C during the study (30 weeks)

          -  Ultrasound (or adequate computed tomography [CT] or magnetic resonance imaging [MRI])
             examination of the liver within 6 months prior to randomization revealing no masses in
             the liver suggestive of hepatocellular carcinoma

          -  Willing to refrain from consuming over-the-counter SAMe and vitamin pills containing
             B-vitamins while participating in this study (30 weeks)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Leukocytes > 1,000/ mm^3

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Liver disease other than from hepatitis C (e.g., hepatitis B, hemochromatosis, fat in
             more than 33% of hepatocytes, if liver biopsy has been performed., etc.); subjects
             with a past history of alcohol use can be enrolled into the study provided they have
             consumed less than 7 drinks/week for the past 12 months

          -  Evidence of mass in liver by radiologic examination that is suggestive of
             hepatocellular carcinoma within 6 months prior to randomization

          -  Model for End-Stage Liver Disease (MELD) score greater than 15 within 60 days prior to
             enrollment

          -  Ascites which is clinically detectable

          -  Use of SAMe during 4 months prior to randomization

          -  Hospitalization within the past 5 years for mania or for bipolar disease

          -  Concurrent use of monoamine oxidase inhibitors (MAO) or other drugs that increase the
             concentration of serotonin

          -  Participants may not be receiving any other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to SAMe

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Children are excluded from this study but will be eligible for future pediatric
             trials, if applicable

          -  Pregnant women are excluded from this study; serum pregnancy must be performed and be
             negative in all women of child bearing potential within 2 weeks prior to enrollment;
             because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with SAMe, breastfeeding should be discontinued
             if the mother is treated with SAMe

          -  Subjects with any medical psychosocial condition that, in the opinion of the
             investigator, could jeopardize the subject's participation in and compliance with the
             study criteria