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S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate in Preventing Liver Cancer in Patients With Chronic Hepatitis C Infection

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00513461
First received: August 6, 2007
Last updated: February 15, 2013
Last verified: February 2013

August 6, 2007
February 15, 2013
October 2007
August 2012   (final data collection date for primary outcome measure)
Change in serum AFP levels [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
Measured using an Food and Drug Administration (FDA)-approved assay. Mean change over time (and 95% confidence intervals) 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.
Change in serum alpha-fetoprotein levels (AFP) from baseline (week 0) to follow-up at week 24
Complete list of historical versions of study NCT00513461 on ClinicalTrials.gov Archive Site
  • Treatment-related changes in additional serum markers for hepatocellular carcinoma [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
    DCP assay will be performed by Wako Laboratories. AFP-L3 assay will be performed by Wako Laboratories using their LiBASys platform.
  • Change in markers of liver disease [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
    ALT and AST measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays. The hepatitis C viral load will be measured in a CAP-certified clinical laboratory using an FDA-approved assay (quantitative assay).
  • Changes in markers of oxidative stress [ Time Frame: Baseline (week 0) to week 24 ] [ Designated as safety issue: No ]
    Serum TNF-alpha will be determined by ELISA with the use of R&D Systems Quantikine High Sensitivity Kit. 8-epi-Prostaglandin F2a is extracted from urine using the C18 Sep Pak and Silica Sep Pak column method. Urine 8-isoprostane concentrations will be determined by ELISA using the BIOYTECH 8-Isoprostane kit. Plasma MDA and 4-HNE will be measured by high performance liquid chromatography (HPLC).
  • Change in SAMe metabolites [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
    Plasma GSH, methionine and homocysteine will be measured using HPLC with fluorescence detection.
  • Safety and tolerability of SAMe [ Time Frame: Up to week 24 ] [ Designated as safety issue: Yes ]
  • Changes in quality of life [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
    Measured using the Short Form (SF)-36 Health Survey (Version II) and the Chronic Liver Disease Questionnaire.
  • Change from baseline to week 24 in other serum markers of hepatocellular carcinoma (i.e., des-gamma carboxyprothrombin or AFP-L3)
  • Change from baseline to week 24 in markers of liver disease (e.g., serum ALT and AST, albumin, and bilirubin) and in hepatitis C viral load
  • Change from baseline to week 24 in markers of oxidative stress (e.g., serum TNF-alpha, malondialdehyde, glutathione, 4-HNE isoprostane, urine F2 isoprostane)
  • Change from baseline to week 24 in SAMe metabolites (e.g., glutathione, methionine, homocysteine, and S-adenosylmethionine)
  • Safety and tolerability as assessed by NCI CTCAE v3.0
  • Health-Related Quality of life as measured at baseline and week 24 by the SF-36 Health Survey (version II) and the Chronic Liver Disease Questionnaire
Not Provided
Not Provided
 
S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate in Preventing Liver Cancer in Patients With Chronic Hepatitis C Infection
A Phase II, Randomized, Controlled Trial of The Safety and Efficacy of S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate (SAMe) in Reducing Serum Alpha-Fetoprotein (AFP) in Patients With Hepatitis C and Moderately Elevated AFP

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Adult Primary Liver Cancer
  • Hepatitis C Infection
  • Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate
    Given PO
    Other Name: SAMe disulfate p-toluene-sulfonate
  • Other: placebo
    Given PO
    Other Name: PLCB
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: immunoenzyme technique
    Correlative studies
    Other Name: immunoenzyme techniques
  • Other: high performance liquid chromatography
    Correlative studies
    Other Name: HPLC
  • Experimental: Arm I (SAMe)
    Patients receive SAMe PO BID for 24 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate
    • Other: laboratory biomarker analysis
    • Other: immunoenzyme technique
    • Other: high performance liquid chromatography
  • Placebo Comparator: Arm II (placebo)
    Patients receive placebo PO QD for weeks 1-4, PO BID for weeks 5-8, and PO TID for weeks 9-24 in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: placebo
    • Other: laboratory biomarker analysis
    • Other: immunoenzyme technique
    • Other: high performance liquid chromatography
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
110
December 2013
August 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00513461
NCI-2009-00897, UCI 06-07, N01CN35160, CDR0000558657
No
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: John Hoefs Chao Family Comprehensive Cancer Center
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP