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Adult Primary Liver CancerPhase 2NCT00513461

Liver Cancer Prevention Trial in Patients With Chronic Hep C Infection

A Phase 2 study testing S-adenosyl-L-methionine disulfate p-toluene-sulfonate, laboratory biomarker analysis and immunoenzyme technique in people with Adult Primary Liver Cancer and Hepatitis C Infection, run by Chao Family Comprehensive Cancer Center at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
S-adenosyl-L-methionine disulfate p-toluene-sulfonate, laboratory biomarker analysis and immunoenzyme technique
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
110 participants
Where
5 sitesUnited States
Study dates
Oct 2007to Dec 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Veterans Administration Long Beach Medical Center

    Long Beach, California, 90822

  • Veterans Administration Los Angeles Healthcare System

    Los Angeles, California, 90073

  • Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of California At San Diego

    San Diego, California, 92103

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

Other trials in United States

About this study

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

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

Read the 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).

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).

  1. 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.

Being tested
S-adenosyl-L-methionine disulfate p-toluene-sulfonate, placebo, laboratory biomarker analysis, immunoenzyme technique, high performance liquid chromatography
Medical subject headings
Carcinoma, Hepatocellular, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • S-adenosyl-L-methionine disulfate p-toluene-sulfonateDrug

    Also called SAMe disulfate p-toluene-sulfonate

    Given PO

  • placeboOther

    Also called PLCB

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

  • immunoenzyme techniqueOther

    Also called immunoenzyme techniques

    Correlative studies

  • high performance liquid chromatographyOther

    Also called HPLC

    Correlative studies

Study groups in NCT00513461
Study groupRoleWhat they receive
Arm I (SAMe)ExperimentalPatients 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.
Receives: Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Other: high performance liquid chromatography
Arm II (placebo)Placebo comparatorPatients 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.
Receives: Other: placebo; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Other: high performance liquid chromatography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to week 24

Secondary outcomes (14)

  1. 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).

    Measured: Baseline to week 24

  2. 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.

    Measured: Baseline to week 24

  3. SAMe

    Change in SAMe levels

    Measured: Baseline to week 24

  4. Change in SAMe Metabolites - S-adenosylhomocysteine (SAH)

    S-adenosylhomocysteine (SAH)

    Measured: Baseline to week 24

  5. Change in SAMe Metabolites - Methionine

    Methionine will be measured using HPLC with fluorescence detection.

    Measured: Baseline to week 24

  6. Change in SAMe Metabolites - Total Homocysteine (tHcy)

    Total homocysteine (tHcy)

    Measured: Baseline to week 24

  7. Change in SAMe Metabolites - Plasma GSH

    Plasma GSH will be measured using HPLC with fluorescence detection.

    Measured: Baseline to week 24

  8. Change in SAMe Metabolites - Malondialdehyde (MDA)

    malondialdehyde

    Measured: Baseline to week 24

  9. 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.

    Measured: Baseline to week 24

  10. 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.

    Measured: Baseline to week 24

  11. 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.

    Measured: Baseline to week 24

  12. HCV RNA

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

    Measured: Baseline to week 24

  13. 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).

    Measured: Baseline to week 24

  14. 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).

    Measured: Baseline to week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionAug 2012
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00513461
Sponsor's protocol ID
UCI 06-07 / NCI-2009-00897
Other IDs
N01CN35160, CDR0000558657, UCI04-3-01
Status last verified
Aug 2018
First submitted
6 Aug 2007
Last updated
10 Aug 2018
Data monitoring committee
No

Publications

  • Morgan TR, Osann K, Bottiglieri T, Pimstone N, Hoefs JC, Hu KQ, Hassanein T, Boyer TD, Kong L, Chen WP, Richmond E, Gonzalez R, Rodriguez LM, Meyskens FL. A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum alpha-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP. Cancer Prev Res (Phila). 2015 Sep;8(9):864-72. doi: 10.1158/1940-6207.CAPR-15-0029. Epub 2015 Jun 30.

    PubMed 26130251

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing S-adenosyl-L-methionine disulfate p-toluene-sulfonate, laboratory biomarker analysis and immunoenzyme technique in people with Adult Primary Liver Cancer and Hepatitis C Infection, run by Chao Family Comprehensive Cancer Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Serum AFP Levels (time frame: Baseline to week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00513461, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2018.

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