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

Sponsors and Collaborators:	Chao Family Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00513461

Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate (SAMe) may keep cancer from forming in patients with advanced liver disease.

PURPOSE: This randomized phase II trial is studying how well SAMe works compared to a placebo in preventing liver cancer in patients with chronic hepatitis C infection.

Condition	Intervention	Phase
Cancer-Related Problem/Condition Liver Cancer	Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate Drug: placebo	Phase II

MedlinePlus related topics: Cancer Hepatitis Hepatitis C Liver Cancer Liver Diseases

Drug Information available for: S-Adenosylmethionine Methionine Toluene

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Placebo Control
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Change in serum alpha-fetoprotein levels (AFP) from baseline (week 0) to follow-up at week 24 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline to week 24 in other serum markers of hepatocellular carcinoma (i.e., des-gamma carboxyprothrombin or AFP-L3) [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
Change from baseline to week 24 in markers of oxidative stress (e.g., serum TNF-alpha, malondialdehyde, glutathione, 4-HNE isoprostane, urine F2 isoprostane) [ Designated as safety issue: No ]
Change from baseline to week 24 in SAMe metabolites (e.g., glutathione, methionine, homocysteine, and S-adenosylmethionine) [ Designated as safety issue: No ]
Safety and tolerability as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
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 [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	October 2007

Arms	Assigned Interventions
Arm I: Experimental Patients receive oral SAMe twice daily on days 1-30.	Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate Given orally
Arm II: Placebo Comparator Patients receive oral placebo twice daily on days 1-30.	Drug: placebo Given orally

Detailed Description:

OBJECTIVES:

Primary

To determine whether treatment with S-adenosyl-L-methionine disulphate p-toluene-sulfonate (SAMe) for 24 weeks reduces serum level of alpha-fetoprotein fraction L-3 in patients with advanced liver disease due to chronic hepatitis C.

Secondary

To determine whether treatment with SAMe for 24 weeks reduces serum levels of des-gamma carboxyprothrombin and alpha-fetoprotein in patients with advanced liver disease due to chronic hepatitis C (hepatocellular carcinoma tumor markers).
To determine whether treatment with SAMe for 24 weeks alters biochemical markers of liver disease (e.g., serum ALT, AST, albumin, or bilirubin) and hepatitis C viral load in patients with advanced liver disease due to chronic hepatitis C (hepatitis C liver disease).
To determine whether treatment with SAMe for 24 weeks reduces serum levels of tumor necrosis factor-alpha, malondialdehyde, 4-hydroxynonenal, and urine level of F2-isoprostane in patients with advanced liver disease due to chronic hepatitis C (oxidative stress).
To determine whether treatment with SAMe for 24 weeks reduces plasma levels of methionine and homocysteine and increases plasma glutathione and SAMe in patients with advanced liver disease due to chronic hepatitis C (SAMe metabolites).
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: This is a prospective, randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating site. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral SAMe twice daily on days 1-30.
Arm II: Patients receive oral placebo twice daily on days 1-30. Patients in both arms also receive an oral multivitamin tablet containing folic acid, B6, and B12 (without iron) (B-50) twice daily on days 1-30. Treatment in both arms continues for up to 24 weeks in the absence of unacceptable toxicity.

Quality of life is assessed at baseline and at weeks 12, 24, and 30. Tobacco use is also assessed at baseline. Patients keep a diary of daily medication use to document consumption of medication throughout the study.

Patients undergo blood and urine collection periodically during study for biomarker correlative studies. Blood and urine samples are analyzed for treatment-related changes in biomarkers of hepatocellular carcinoma, liver disease, oxidative stress, and SAMe metabolites. Laboratory studies used to assess these biomarkers include ELISA and other enzyme immunoassays and high performance liquid chromatography.

After completion of study therapy, patients are followed at 6 weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

Chronic hepatitis C infection diagnosed by presence of hepatitis C RNA in serum by FDA-approved test of HCV RNA
Evidence of advanced liver disease based on ≥ 1 of the following:
- Platelet count < 150,000/mm³
- AST/ALT ratio > 0.75
- Liver biopsy demonstrating bridging fibrosis or cirrhosis
Ultrasound (or adequate CT scan or MRI) examination of the liver within 6 months prior to randomization revealing no masses in the liver suggestive of hepatocellular carcinoma
Serum alpha-fetoprotein 15 -100 ng/mL
ALT > 1.5 times upper limit of normal
No significant alcohol use (i.e., 7 or more drinks per week) for the past 12 months

Exclusion criteria:

Liver disease other than from hepatitis C (e.g., hepatitis B, hemochromatosis, or fat in more than 33% of hepatocytes [if liver biopsy has been performed])
Serum AFP > 100 ng/dL within 6 months prior to entry into the study
Model End-Stage Liver Disease score > 15 within 60 days prior to enrollment
Ascites within the past 6 months
Serum creatinine > 1.6 mg/dL within 6 weeks prior to enrollment

PATIENT CHARACTERISTICS:

Inclusion criteria:

See Disease Characteristics
ECOG performance status 0-2
Leukocytes > 2,000/mm³
ANC > 1,000/mm³
Platelet count > 50,000/mm³
Total bilirubin < 2.5 mg/dL
Creatinine ≤ 1.6 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use adequate contraception

Exclusion criteria:

Hospitalization within the past 5 years for mania or for bipolar disease
History of allergic reactions attributed to compounds of similar chemical or biological composition to S-adenosyl-L-methionine disulphate p-toluene-sulfonate (SAMe)
Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
Psychiatric illness or social situation that would limit compliance with study requirements
Medical psychosocial condition that, in the opinion of the investigator, could jeopardize the patient's participation in and compliance with the study criteria

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

Willing to refrain from consuming over-the-counter SAMe and vitamin pills containing B-vitamins while participating in this study (30 weeks)

Exclusion criteria:

Interferon, peginterferon, or ribavirin within the past 4 months or concurrently during study
Treatment with over-the-counter SAMe within the past 4 months
Concurrent monoamine oxidase inhibitors or other drugs that increase the concentration of serotonin (e.g., meperidine, pentazocine, tramadol, and the non-prescription drugs 5-hydroxytryptophan, Hawaiian baby woodrose, L-tryptophan, St. John's wort, or dextromethorphan)
Other concurrent investigational agents
Concurrent diuretics to treat ascites
Concurrent over-the-counter SAMe or vitamin pills containing B-vitamins
Anticipated treatment for hepatitis C during the study (30 weeks)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00513461

Locations

United States, Arizona
Arizona Cancer Center at University of Arizona Health Sciences Center	Recruiting
Tucson, Arizona, United States, 85724-5024
Contact: Clinical Trials Office - Arizona Cancer Center at University o 520-626-9008
United States, California
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Recruiting
Orange, California, United States, 92868
Contact: Frank L. Meyskens, MD, FACP 714-456-6310 flmeyske@uci.edu
Rebecca and John Moores UCSD Cancer Center	Recruiting
La Jolla, California, United States, 92093-0658
Contact: Clinical Trials Office - Rebecca and John Moores UCSD Cancer 858-822-5354 cancercto@ucsd.edu
Veterans Affairs Medical Center - Long Beach	Recruiting
Long Beach, California, United States, 90822
Contact: Timothy R. Morgan, MD 562-826-5756
Veterans Affairs Medical Center - West Los Angeles	Recruiting
Los Angeles, California, United States, 90073
Contact: Neville Pimstone, MD, PhD, FACP, FCP 310-478-3711

Sponsors and Collaborators

Chao Family Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Timothy R. Morgan, MD	Veterans Affairs Medical Center - Long Beach
Principal Investigator:	Frank L. Meyskens, MD, FACP	Chao Family Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000558657, UCIRVINE-UCI04-3-01, UCIRVINE-UCI-HS-2006-4593
Study First Received:	August 6, 2007
Last Updated:	December 10, 2008
ClinicalTrials.gov Identifier:	NCT00513461
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult primary hepatocellular carcinoma
adult primary liver cancer
infection

Study placed in the following topic categories:

Liver Diseases
Digestive System Neoplasms
Hepatitis, Chronic
Carcinoma, Hepatocellular
Liver neoplasms
Hepatitis, Viral, Human
Carcinoma
Liver Neoplasms

Hepatitis
Virus Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Hepatitis C
Hepatitis C, Chronic
Hepatocellular carcinoma

Additional relevant MeSH terms:

Neoplasms
RNA Virus Infections
Neoplasms by Site
Flaviviridae Infections

ClinicalTrials.gov processed this record on January 15, 2009