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Liver Cancer Prevention Trial in Patients With Chronic Hep C Infection

Sponsor
Chao Family Comprehensive Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00513461
Collaborator
National Cancer Institute (NCI) (NIH)
110
Enrollment
5
Locations
2
Arms
74
Duration (Months)
22
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease Intervention/Treatment Phase
  • Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate
  • Other: placebo
  • Other: laboratory biomarker analysis
  • Other: immunoenzyme technique
  • Other: high performance liquid chromatography
 Phase 2

Detailed Description

PRIMARY OBJECTIVE:
  1. 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:

  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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 Design

Study Type:
Interventional
Actual Enrollment :
110 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Prevention
Official Title:
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
Study Start Date :
Oct 1, 2007
Actual Primary Completion Date :
Aug 1, 2012
Actual Study Completion Date :
Dec 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (SAMe)

Patients receive SAMe 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.

Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate
Given PO
Other Names:
  • SAMe disulfate p-toluene-sulfonate

    • Other: laboratory biomarker analysis
    Correlative studies

    Other: immunoenzyme technique
    Correlative studies
    Other Names:
  • immunoenzyme techniques

    • Other: high performance liquid chromatography
    Correlative studies
    Other Names:
  • HPLC

    		•
    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.

    Other: placebo
    Given PO
    Other Names:
  • PLCB

    • Other: laboratory biomarker analysis
    Correlative studies

    Other: immunoenzyme technique
    Correlative studies
    Other Names:
  • immunoenzyme techniques

    • Other: high performance liquid chromatography
    Correlative studies
    Other Names:
  • HPLC

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Serum AFP Levels [Baseline to week 24]

      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.

    Secondary Outcome Measures

    1. Treatment-related Changes in Serum DCP for Hepatocellular Carcinoma [Baseline to week 24]

      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).

    2. Treatment-related Changes in Serum AFP-L3 (Expressed as the Percentage of Total AFTP) for Hepatocellular Carcinoma [Baseline to week 24]

      AFP-L3 assay will be performed by Wako Laboratories using their LiBASys platform.

    3. SAMe [Baseline to week 24]

      Change in SAMe levels

    4. Change in SAMe Metabolites - S-adenosylhomocysteine (SAH) [Baseline to week 24]

      S-adenosylhomocysteine (SAH)

    5. Change in SAMe Metabolites - Methionine [Baseline to week 24]

      Methionine will be measured using HPLC with fluorescence detection.

    6. Change in SAMe Metabolites - Total Homocysteine (tHcy) [Baseline to week 24]

      Total homocysteine (tHcy)

    7. Change in SAMe Metabolites - Plasma GSH [Baseline to week 24]

      Plasma GSH will be measured using HPLC with fluorescence detection.

    8. Change in SAMe Metabolites - Malondialdehyde (MDA) [Baseline to week 24]

      malondialdehyde

    9. Change in SAMe Metabolites - 4-hydroxynonenal (4-HNE) [Baseline to week 24]

      Serum marker of oxidative stress. One mechanism by which SAMe is hypothesized to be beneficial is by reducing oxidative stress.

    10. Change in Markers of Liver Disease - AST [Baseline to week 24]

      AST measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays.

    11. Change in Markers of Liver Disease - ALT [Baseline to week 24]

      ALT measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays.

    12. HCV RNA [Baseline to week 24]

      Change in HCV RNA levels. Serum level of HVC RNA was measured using COBAS TaqMan HCV test (Roche Molecular Systems).

    13. Changes in Quality of Life - Physical Score [Baseline to week 24]

      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).

    14. Changes in Quality of Life - Mental Score [Baseline to week 24]

      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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arizona Health Sciences Center Tucson Arizona United States 85724
    2 Veterans Administration Long Beach Medical Center Long Beach California United States 90822
    3 Veterans Administration Los Angeles Healthcare System Los Angeles California United States 90073
    4 Chao Family Comprehensive Cancer Center Orange California United States 92868
    5 University of California At San Diego San Diego California United States 92103

    Sponsors and Collaborators

    • Chao Family Comprehensive Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: John Hoefs, Chao Family Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Chao Family Comprehensive Cancer Center, Cancer Center, University of California, Irvine
    ClinicalTrials.gov Identifier:
    NCT00513461
    Other Study ID Numbers:
    • UCI 06-07 / NCI-2009-00897
    • N01CN35160
    • CDR0000558657
    • UCI04-3-01
    First Posted:
    Aug 8, 2007
    Last Update Posted:
    Aug 10, 2018
    Last Verified:
    Aug 1, 2018
    Additional relevant MeSH terms:
    Infections
    Hepatitis C
    Liver Neoplasms
    Hepatitis

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Period Title: Overall Study
    STARTED 57 53
    COMPLETED 44 43
    NOT COMPLETED 13 10

    Baseline Characteristics

    Arm/Group Title Arm I (SAMe) Arm II (Placebo) Total
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies Total of all reporting groups
    Overall Participants 57 53 110
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.5
    (4.9)
    57.2
    (5.8)
    57.88
    (5.33)
    Sex: Female, Male (Count of Participants)
    Female
    9
    15.8%
    6
    11.3%
    15
    13.6%
    Male
    48
    84.2%
    47
    88.7%
    95
    86.4%

    Outcome Measures

    1. Primary Outcome
    Title Change in Serum AFP Levels
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data anlysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 40
    Mean (Standard Deviation) [ng/mL]
    -1.928
    (20.304)
    5.855
    (29.207)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm I (SAMe), Arm II (Placebo)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.160
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 7.78
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Treatment-related Changes in Serum DCP for Hepatocellular Carcinoma
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 27 26
    Mean (Standard Deviation) [ng/mL]
    0.259
    (0.976)
    0.647
    (1.491)
    3. Secondary Outcome
    Title Treatment-related Changes in Serum AFP-L3 (Expressed as the Percentage of Total AFTP) for Hepatocellular Carcinoma
    Description AFP-L3 assay will be performed by Wako Laboratories using their LiBASys platform.
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 27 26
    Mean (Standard Deviation) [percentage of AFP-L3/AFP]
    0.144
    (1.146)
    0.335
    (3.486)
    4. Secondary Outcome
    Title SAMe
    Description Change in SAMe levels
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 41
    Mean (Standard Deviation) [nmol/L]
    414.242
    (744.373)
    -9.085
    (54.621)
    5. Secondary Outcome
    Title Change in SAMe Metabolites - S-adenosylhomocysteine (SAH)
    Description S-adenosylhomocysteine (SAH)
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 41
    Mean (Standard Deviation) [nmol/L]
    16.326
    (28.212)
    -3.456
    (13.104)
    6. Secondary Outcome
    Title Change in SAMe Metabolites - Methionine
    Description Methionine will be measured using HPLC with fluorescence detection.
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 41
    Mean (Standard Deviation) [µmol/L]
    0.421
    (18.794)
    -2.894
    (23.669)
    7. Secondary Outcome
    Title Change in SAMe Metabolites - Total Homocysteine (tHcy)
    Description Total homocysteine (tHcy)
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 41
    Mean (Standard Deviation) [µmol/L]
    0.266
    (2.394)
    -0.677
    (2.478)
    8. Secondary Outcome
    Title Change in SAMe Metabolites - Plasma GSH
    Description Plasma GSH will be measured using HPLC with fluorescence detection.
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 41
    Mean (Standard Deviation) [µmol/L]
    0.455
    (1.425)
    0.285
    (1.23)
    9. Secondary Outcome
    Title Change in SAMe Metabolites - Malondialdehyde (MDA)
    Description malondialdehyde
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 41
    Mean (Standard Deviation) [µmol/L]
    -0.007
    (0.848)
    -0.002
    (1.162)
    10. Secondary Outcome
    Title Change in SAMe Metabolites - 4-hydroxynonenal (4-HNE)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 41
    Mean (Standard Deviation) [µg/mL]
    -0.185
    (0.716)
    -0.032
    (0.448)
    11. Secondary Outcome
    Title Change in Markers of Liver Disease - AST
    Description AST measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays.
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 44 43
    Mean (Standard Deviation) [IU/L]
    -0.755
    (37.531)
    1.723
    (40.709)
    12. Secondary Outcome
    Title Change in Markers of Liver Disease - ALT
    Description ALT measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays.
    Time Frame Baseline to week 24

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 44 43
    Mean (Standard Deviation) [IU/L]
    -9.548
    (34.786)
    0.019
    (41.165)
    13. Secondary Outcome
    Title HCV RNA
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 36 35
    Mean (Standard Deviation) [IU/mL]
    -259327.69
    (3084015.42)
    -19968.89
    (2425010.48)
    14. Secondary Outcome
    Title Changes in Quality of Life - Physical Score
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 43
    Mean (Standard Deviation) [units on a scale]
    -0.4
    (11.73)
    0.03
    (13.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm I (SAMe), Arm II (Placebo)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.878
    Comments
    Method Two-Group t-test
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.43
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Changes in Quality of Life - Mental Score
    Description 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

    Outcome Measure Data

    Analysis Population Description
    All subjects who completed the week 24 visit as planned were included in the data analysis. The number of subjects in each analysis differed slightly because the number of subjects with data at both time points (i.e., week 0 and week 24) varied depending on the outcome measured.
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    Measure Participants 43 43
    Mean (Standard Deviation) [scores on a scale]
    0.83
    (15.06)
    -2.83
    (11.76)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm I (SAMe), Arm II (Placebo)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.212
    Comments
    Method Two-Group t-test
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -3.66
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Through study completion, an average of 30 weeks.
    Adverse Event Reporting Description
    Arm/Group Title Arm I (SAMe) Arm II (Placebo)
    Arm/Group Description Patients receive SAMe 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. S-adenosyl-L-methionine disulfate p-toluene-sulfonate: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies 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. placebo: Given PO laboratory biomarker analysis: Correlative studies immunoenzyme technique: Correlative studies high performance liquid chromatography: Correlative studies
    All Cause Mortality
    Arm I (SAMe) Arm II (Placebo)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Arm I (SAMe) Arm II (Placebo)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/57 (8.8%) 3/53 (5.7%)
    Cardiac disorders
    NON-ST ELEVATION MIOCARDIAL INFARCTION 1/57 (1.8%) 1 0/53 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL DISCOMFORT 1/57 (1.8%) 1 0/53 (0%) 0
    ABDOMINAL PAIN.STATUS POST SPLENIC ARTERY EMBOLIZATION 1/57 (1.8%) 1 0/53 (0%) 0
    SMALL BOWEL INFLAMATION 1/57 (1.8%) 1 0/53 (0%) 0
    Hepatobiliary disorders
    HEPATOCELLULAR CARCINOMA 0/57 (0%) 0 1/53 (1.9%) 1
    SPLENOMEGALY SECONDARY TO PORTAL HYPERTENSION 1/57 (1.8%) 1 0/53 (0%) 0
    Infections and infestations
    ABDOMINAL CELLULITIS 0/57 (0%) 0 1/53 (1.9%) 1
    LEFT THIGH ABSCESS 0/57 (0%) 0 1/53 (1.9%) 1
    PNEUMONIA 1/57 (1.8%) 1 0/53 (0%) 0
    Renal and urinary disorders
    NEPHROTIC SYNDROME 1/57 (1.8%) 1 0/53 (0%) 0
    Vascular disorders
    ANGIOPLASTY OF LEFT HYPOGASTRIC ARTERY, EXTERNAL ILIAC STENT PLACEMENT FOR LEFT LEG 0/57 (0%) 0 1/53 (1.9%) 1
    Other (Not Including Serious) Adverse Events
    Arm I (SAMe) Arm II (Placebo)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 51/57 (89.5%) 46/53 (86.8%)
    Blood and lymphatic system disorders
    SWELLING OF ANKLES 1/57 (1.8%) 1 0/53 (0%) 0
    Ear and labyrinth disorders
    CLICKING SOUND IN THE HEAD 1/57 (1.8%) 1 0/53 (0%) 0
    EAR PAIN 0/57 (0%) 0 1/53 (1.9%) 1
    EARS RINGING 0/57 (0%) 0 1/53 (1.9%) 1
    TINNITUS 0/57 (0%) 0 1/53 (1.9%) 1
    Endocrine disorders
    BORDERLINE DIABETES 1/57 (1.8%) 1 0/53 (0%) 0
    DIABETES MELLITUS 0/57 (0%) 0 1/53 (1.9%) 1
    HOT FLUSHES 1/57 (1.8%) 1 0/53 (0%) 0
    WORSENING OF BASELINE DIABETES MELLITUS 0/57 (0%) 0 1/53 (1.9%) 1
    Eye disorders
    BLURRED VISION 0/57 (0%) 0 1/53 (1.9%) 1
    EYE PAIN 0/57 (0%) 0 1/53 (1.9%) 1
    EYES HURT 1/57 (1.8%) 1 0/53 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL CRAMPS 0/57 (0%) 0 1/53 (1.9%) 1
    ABDOMINAL DISCOMFORT 1/57 (1.8%) 1 0/53 (0%) 0
    ASCITES 1/57 (1.8%) 1 2/53 (3.8%) 2
    BAD GAS 1/57 (1.8%) 1 1/53 (1.9%) 1
    CHRONIC ASCITES 0/57 (0%) 0 1/53 (1.9%) 1
    CHRONIC GASTRITIS 0/57 (0%) 0 1/53 (1.9%) 1
    CONSTIPATION 12/57 (21.1%) 17 5/53 (9.4%) 6
    DENTAL IMPLANT SURGERY 1/57 (1.8%) 1 0/53 (0%) 0
    DIARRHEA 20/57 (35.1%) 31 13/53 (24.5%) 17
    DIARRHEA 4-6 STOOLS/DAY 1/57 (1.8%) 1 0/53 (0%) 0
    DIFFUSE ABDOMINAL PAIN 0/57 (0%) 0 1/53 (1.9%) 1
    DRY MOUTH 10/57 (17.5%) 10 12/53 (22.6%) 13
    DRY MOUTH/SALIVARY GLAND 1/57 (1.8%) 1 0/53 (0%) 0
    DRYNESS OF MOUTH 1/57 (1.8%) 1 0/53 (0%) 0
    EXTRA GAS FLATULENCE 0/57 (0%) 0 1/53 (1.9%) 1
    FLATULENCE 19/57 (33.3%) 22 22/53 (41.5%) 25
    FOOD POISONING 2/57 (3.5%) 2 0/53 (0%) 0
    GAS-FLATULENCE 1/57 (1.8%) 1 1/53 (1.9%) 1
    GI CONSTIPATION 1/57 (1.8%) 1 0/53 (0%) 0
    GUM BLEEDING 0/57 (0%) 0 1/53 (1.9%) 1
    HEARTBURN 7/57 (12.3%) 9 4/53 (7.5%) 4
    INCREASE IN FLATULENCE 1/57 (1.8%) 1 0/53 (0%) 0
    INCREASE NUMBER OF STOOLS 1/57 (1.8%) 1 0/53 (0%) 0
    INCREASED DIARRHEA 0/57 (0%) 0 1/53 (1.9%) 1
    INCREASED FLATULENCE 0/57 (0%) 0 1/53 (1.9%) 1
    INCREASED STOMACH PAIN 1/57 (1.8%) 1 0/53 (0%) 0
    INTESTINAL FLU 1/57 (1.8%) 1 0/53 (0%) 0
    NAUSEA 18/57 (31.6%) 20 7/53 (13.2%) 8
    QUEASINESS 0/57 (0%) 0 1/53 (1.9%) 1
    STOMACH ACHE 1/57 (1.8%) 1 0/53 (0%) 0
    STOMACH CRAMPS 1/57 (1.8%) 3 0/53 (0%) 0
    STOMACH FLU 0/57 (0%) 0 1/53 (1.9%) 1
    STOMACH PAIN 21/57 (36.8%) 28 9/53 (17%) 10
    TOOTH EXTRACTION 1/57 (1.8%) 1 0/53 (0%) 0
    TOOTHACHE 1/57 (1.8%) 1 0/53 (0%) 0
    UPSET STOMACH 0/57 (0%) 0 1/53 (1.9%) 1
    VOMITING 5/57 (8.8%) 6 4/53 (7.5%) 4
    General disorders
    CHILLS 1/57 (1.8%) 1 0/53 (0%) 0
    COLD 4/57 (7%) 5 2/53 (3.8%) 2
    COMMON COLD 1/57 (1.8%) 1 1/53 (1.9%) 1
    FATIGUE 15/57 (26.3%) 19 9/53 (17%) 11
    FEVER 1/57 (1.8%) 1 1/53 (1.9%) 1
    FLU 1/57 (1.8%) 1 0/53 (0%) 0
    FLU-LIKE SYMPTOMS 0/57 (0%) 0 4/53 (7.5%) 4
    TIREDNESS FATIGUE 0/57 (0%) 0 1/53 (1.9%) 1
    Immune system disorders
    ALLERGIC RHINITIS 0/57 (0%) 0 1/53 (1.9%) 1
    FACIAL SWELLING OF ALLERGIC ORIGIN 1/57 (1.8%) 1 0/53 (0%) 0
    Infections and infestations
    INFECTED SEBACEOUS CYST R. AXILA 1/57 (1.8%) 1 0/53 (0%) 0
    PNEUMONIA 0/57 (0%) 0 1/53 (1.9%) 1
    VAGINAL YEAST INFECTION 0/57 (0%) 0 1/53 (1.9%) 1
    VIRAL INFECTION INCLUDING COUGHING 1/57 (1.8%) 1 0/53 (0%) 0
    Investigations
    ELEVATED CREATININE 1/57 (1.8%) 1 0/53 (0%) 0
    ELEVATED INR 1/57 (1.8%) 1 0/53 (0%) 0
    VITAMIN D DEFICIENCY 0/57 (0%) 0 1/53 (1.9%) 1
    WEIGHT GAIN 1/57 (1.8%) 1 0/53 (0%) 0
    Metabolism and nutrition disorders
    HUNGRIER 0/57 (0%) 0 1/53 (1.9%) 2
    HYPOKALEMIA 1/57 (1.8%) 1 0/53 (0%) 0
    Musculoskeletal and connective tissue disorders
    ARTHRITIS PAIN, KNEES 0/57 (0%) 0 1/53 (1.9%) 1
    ARTHRITIS PAIN, LOWER BACK 0/57 (0%) 0 1/53 (1.9%) 1
    BROKEN TOOTH-UNCOMPLICATED 0/57 (0%) 0 1/53 (1.9%) 1
    DISLOCATION OF LEFT SHOULDER 0/57 (0%) 0 1/53 (1.9%) 1
    FALL, HIP AND BACK PAIN 0/57 (0%) 0 1/53 (1.9%) 1
    FEET AND LEGS CRAMPS 1/57 (1.8%) 1 0/53 (0%) 0
    FRACTURE 5TH R METACARPAL 1/57 (1.8%) 1 0/53 (0%) 0
    JOINT PAIN 1/57 (1.8%) 1 0/53 (0%) 0
    KNEE PAIN 0/57 (0%) 0 1/53 (1.9%) 1
    LEFT LEG VASCULAR CLAUDICATION 0/57 (0%) 0 1/53 (1.9%) 2
    LEFT SIDE PAIN 0/57 (0%) 0 2/53 (3.8%) 2
    LEG CRAMPS 1/57 (1.8%) 1 2/53 (3.8%) 2
    LOWER BACK PAIN 1/57 (1.8%) 1 0/53 (0%) 0
    LOWER BACK SURGERY 1/57 (1.8%) 1 0/53 (0%) 0
    LOWER BACKACHE 1/57 (1.8%) 1 0/53 (0%) 0
    LOWER EXTREMITY EDEMA 0/57 (0%) 0 2/53 (3.8%) 2
    MUSCLE CRAMPS 1/57 (1.8%) 1 1/53 (1.9%) 1
    MUSCLE CRAMPS OF BOTH LEGS 0/57 (0%) 0 1/53 (1.9%) 1
    MUSCLE MOVEMENT 0/57 (0%) 0 1/53 (1.9%) 1
    MUSCULOSKELETAL PAIN 0/57 (0%) 0 1/53 (1.9%) 1
    MUSCULOSKELETAL PAIN (NECK) 0/57 (0%) 0 1/53 (1.9%) 1
    MYALGIA 1/57 (1.8%) 1 0/53 (0%) 0
    NECK PAIN 1/57 (1.8%) 1 1/53 (1.9%) 1
    OLECRANON BURSITIS 1/57 (1.8%) 1 0/53 (0%) 0
    PAIN IN BOTH HANDS AND FEET 0/57 (0%) 0 1/53 (1.9%) 1
    PAIN IN KNEE 0/57 (0%) 0 1/53 (1.9%) 1
    PAIN LEFT SIDE OF CHEST 0/57 (0%) 0 1/53 (1.9%) 1
    PAIN ON ANKLE JOINTS 0/57 (0%) 0 1/53 (1.9%) 1
    PAIN ON HIP 0/57 (0%) 0 1/53 (1.9%) 1
    PAIN ON KNEE 0/57 (0%) 0 1/53 (1.9%) 1
    SPRAINED ANKLE 0/57 (0%) 0 1/53 (1.9%) 1
    STIFF NECK 0/57 (0%) 0 1/53 (1.9%) 1
    STIFFNESS OF JOINTS 0/57 (0%) 0 1/53 (1.9%) 1
    WEAKNESS 1/57 (1.8%) 1 0/53 (0%) 0
    WORSENING OF BACK PAIN 1/57 (1.8%) 1 0/53 (0%) 0
    Nervous system disorders
    BLACK OUT 0/57 (0%) 0 1/53 (1.9%) 1
    DIZZINESS 5/57 (8.8%) 6 4/53 (7.5%) 6
    FORGETFULNESS 0/57 (0%) 0 1/53 (1.9%) 1
    HEADACHE 13/57 (22.8%) 16 11/53 (20.8%) 13
    HEADACHE-SINUS 0/57 (0%) 0 1/53 (1.9%) 1
    HEPATIC ENCEPHALOPATHY 0/57 (0%) 0 1/53 (1.9%) 1
    INTERMITTENT HEADACHE 1/57 (1.8%) 1 1/53 (1.9%) 1
    INVOLUNTARY MOVEMENT 1/57 (1.8%) 1 1/53 (1.9%) 1
    MEMORY LOSS 0/57 (0%) 0 1/53 (1.9%) 1
    PINCHED NERVE 0/57 (0%) 0 1/53 (1.9%) 1
    TICS 0/57 (0%) 0 1/53 (1.9%) 1
    Psychiatric disorders
    ANXIETY 3/57 (5.3%) 3 0/53 (0%) 0
    DECREASED INSOMNIA 1/57 (1.8%) 1 0/53 (0%) 0
    DEPRESSION 1/57 (1.8%) 1 1/53 (1.9%) 1
    HAPPIER 0/57 (0%) 0 1/53 (1.9%) 1
    HYPERSOMNIA 2/57 (3.5%) 2 0/53 (0%) 0
    INSOMNIA 9/57 (15.8%) 11 8/53 (15.1%) 9
    IRRITABILITY 0/57 (0%) 0 1/53 (1.9%) 1
    MANIA 1/57 (1.8%) 1 2/53 (3.8%) 5
    MOOD ALTERATION 2/57 (3.5%) 7 2/53 (3.8%) 2
    MOOD ALTERATION DEPRESSION 1/57 (1.8%) 2 0/53 (0%) 0
    MOOD ALTERATION-ANXIETY 1/57 (1.8%) 1 0/53 (0%) 0
    MOOD ALTERATION-HAPPY 1/57 (1.8%) 1 0/53 (0%) 0
    MOOD ALTERATION:ANXIETY 0/57 (0%) 0 1/53 (1.9%) 1
    RESTLESSNESS 0/57 (0%) 0 1/53 (1.9%) 1
    VIVID DREAMS 0/57 (0%) 0 1/53 (1.9%) 1
    WORSENING OF ANXIETY 1/57 (1.8%) 1 0/53 (0%) 0
    Renal and urinary disorders
    DARK COLORED URINE 0/57 (0%) 0 1/53 (1.9%) 1
    ELEVATED AFP 0/57 (0%) 0 1/53 (1.9%) 1
    INCREASE PEE 0/57 (0%) 0 1/53 (1.9%) 1
    INCREASED URINATION 12/57 (21.1%) 13 9/53 (17%) 10
    URINE ODOR 0/57 (0%) 0 1/53 (1.9%) 1
    Reproductive system and breast disorders
    BREAST TENDERNESS 1/57 (1.8%) 1 0/53 (0%) 0
    VAGINAL IRRITATION 1/57 (1.8%) 1 0/53 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    BLEEDING ESPHAGEAL VARICES 0/57 (0%) 0 1/53 (1.9%) 1
    BLOOD IN STOOLS 1/57 (1.8%) 1 0/53 (0%) 0
    BRONCHITIS 0/57 (0%) 0 1/53 (1.9%) 1
    CHEST CONGESTION 0/57 (0%) 0 1/53 (1.9%) 1
    COUGH 3/57 (5.3%) 3 0/53 (0%) 0
    NOSE BLEEDING 0/57 (0%) 0 1/53 (1.9%) 1
    RESPIRATORY TRACT INFECTION 0/57 (0%) 0 1/53 (1.9%) 1
    SHORTNESS OF BREATH 1/57 (1.8%) 1 0/53 (0%) 0
    SINUS PAIN 0/57 (0%) 0 1/53 (1.9%) 1
    SINUSITIS 1/57 (1.8%) 1 0/53 (0%) 0
    Skin and subcutaneous tissue disorders
    ANAL IRRITATION 1/57 (1.8%) 1 0/53 (0%) 0
    BRUISING R LEG 0/57 (0%) 0 1/53 (1.9%) 1
    CELLULITIS 0/57 (0%) 0 2/53 (3.8%) 2
    CYST ON PATELLA 1/57 (1.8%) 1 0/53 (0%) 0
    HAIR LOSS 0/57 (0%) 0 1/53 (1.9%) 1
    INCREASED SWEATING 1/57 (1.8%) 1 0/53 (0%) 0
    ITCHINESS ALL OVER THE BODY 1/57 (1.8%) 1 1/53 (1.9%) 1
    ITCHING 1/57 (1.8%) 1 1/53 (1.9%) 1
    MACULOPAPULAR RASH ON TORSO 1/57 (1.8%) 1 0/53 (0%) 0
    MILD RASH 1/57 (1.8%) 1 0/53 (0%) 0
    RASH 1/57 (1.8%) 1 2/53 (3.8%) 2
    RASH ON BOTH ARMS 0/57 (0%) 0 1/53 (1.9%) 1
    RASH ON EXTREMETIES 0/57 (0%) 0 1/53 (1.9%) 1
    SKIN RASH 0/57 (0%) 0 1/53 (1.9%) 2
    SWEATING 5/57 (8.8%) 5 6/53 (11.3%) 9
    SWEATING "NIGHT" 1/57 (1.8%) 1 0/53 (0%) 0
    ULCERATION OF THE LIP 1/57 (1.8%) 1 0/53 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Dr. Timothy R. Morgan
    Organization University of California, Irvine
    Phone 562-826-5756
    Email timothy.morgan@va.gov
    Responsible Party:
    Chao Family Comprehensive Cancer Center, Cancer Center, University of California, Irvine
    ClinicalTrials.gov Identifier:
    NCT00513461
    Other Study ID Numbers:
    • UCI 06-07 / NCI-2009-00897
    • N01CN35160
    • CDR0000558657
    • UCI04-3-01
    First Posted:
    Aug 8, 2007
    Last Update Posted:
    Aug 10, 2018
    Last Verified:
    Aug 1, 2018