Liver Cancer Prevention Trial in Patients With Chronic Hep C Infection

NCT00513461 | Completed Phase 2 Results

• 4 other identifiers: UCI 06-07 / NCI-2009-00897N01CN35160CDR0000558657UCI04-3-01
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 5

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

Conditions

Adult Primary Liver Cancer; Hepatitis C Infection

Outcome Measures

Primary Outcomes (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.

  Baseline to week 24

Secondary Outcomes (14)

• Treatment-related Changes in Serum DCP for Hepatocellular Carcinoma

  Baseline to week 24

• Treatment-related Changes in Serum AFP-L3 (Expressed as the Percentage of Total AFTP) for Hepatocellular Carcinoma

  Baseline to week 24

• SAMe

  Baseline to week 24

• Change in SAMe Metabolites - S-adenosylhomocysteine (SAH)

  Baseline to week 24

• Change in SAMe Metabolites - Methionine

  Baseline to week 24

Study Arms (2)

Arm I (SAMe)

EXPERIMENTAL

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; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Other: high performance liquid chromatography

Arm II (placebo)

PLACEBO COMPARATOR

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; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Other: high performance liquid chromatography

Interventions

S-adenosyl-L-methionine disulfate p-toluene-sulfonate DRUG

Given PO

Also known as: SAMe disulfate p-toluene-sulfonate

Arm I (SAMe)

placebo OTHER

Given PO

Also known as: PLCB

Arm II (placebo)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (SAMe); Arm II (placebo)

immunoenzyme technique OTHER

Correlative studies

Also known as: immunoenzyme techniques

Arm I (SAMe); Arm II (placebo)

high performance liquid chromatography OTHER

Correlative studies

Also known as: HPLC

Arm I (SAMe); Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chao Family Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Veterans Administration Long Beach Medical Center

Long Beach, California, 90822, United States

Location

Veterans Administration Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

University of California At San Diego

San Diego, California, 92103, United States

Location

Related Publications (1)

• 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.

  PMID: 26130251 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis C

Interventions

Immunoenzyme Techniques; Chromatography, High Pressure Liquid

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis

Intervention Hierarchy (Ancestors)

Immunoassay; Immunologic Techniques; Investigative Techniques; Immunohistochemistry; Molecular Probe Techniques; Chromatography, Liquid; Chromatography; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Dr. Timothy R. Morgan
• Organization: University of California, Irvine

timothy.morgan@va.gov

562-826-5756

Study Officials

• John Hoefs

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Cancer Center

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 8, 2007
• Study Start: October 1, 2007
• Primary Completion: August 1, 2012
• Study Completion: December 1, 2013
• Last Updated: August 10, 2018
• Results First Posted: August 10, 2018

Record last verified: 2018-08

Locations

US (5)