Clinical trial NCT00834860: Peginterferon Plus Ribavirin for Hepatitis C Patients Concomitant With Hepatocellular Carcinoma
Official title: The Response and Outcomes of Pegylated Interferon Plus Ribavirin Combination Therapy for Chronic Hepatitis C Patients Concomitant With Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis C
Hepatocellular Carcinoma
Keywords: chronic hepatitis C
sustained virological response
peginterferon
ribavirin
neoplasm
Lead sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital
Sponsor class: OTHER
First posted: 2009-02-03
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Combination therapy with pegylated interferon-alpha plus ribavirin has greatly improved the treatment efficacy and is the mainstream of treatment for chronic hepatitis C infection. The efficacy and safety of pegylated interferon-alpha plus ribavirin combination therapy and its impact on the outcome in chronic hepatitis C patients concomitant with hepatocellular carcinoma deserve to be elucidated.

The purposes of this study are:

1. To evaluate the efficacy and safety of pegylated interferon-alpha 2a plus ribavirin combination therapy in chronic hepatitis C patients concomitant with hepatocellular carcinoma.
2. To investigate the role of baseline and on-treatment factors on the response to pegylated interferon-alpha 2a plus ribavirin combination therapy in chronic hepatitis C patients concomitant with hepatocellular carcinoma.

Detailed description: A prospective, hospital-based study enrolling 100 chronic hepatitis C patients concomitant with hepatocellular carcinoma and other sex- and age-matched 100 chronic hepatitis C patients without malignancy will be conducted. The 100 chronic hepatitis C patients concomitant with hepatocellular carcinoma will receive pegylated interferon-alpha 2a plus ribavirin combination therapy at remission phase after oncological treatments and/or interventions. The other 100 chronic hepatitis C patients without malignancy receiving the same antiviral therapy will serve as controls. The primary outcome measurement is sustained virological response and safety, whilst the secondary measurement is rapid virological and early virological response.

Eligibility criteria: Inclusion Criteria:

* Male and female patients \>18 years of age
* Histopathological diagnosis of hepatocellular carcinoma \>3 months before entry (Arm A)
* Received curative therapies, including surgery, ablation therapy or liver transplantation \>3 months before entry (ArmA)
* No evidence of hepatocellular carcinoma by imaging or histopathological studies at entry
* Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin
* Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
* Detectable serum HCV-RNA
* Liver biopsy findings consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis (Exception: hemophiliacs in whom biopsy is medically contra-indicated do not require biopsy.)
* Compensated liver disease (Child-Pugh Grade A clinical classification)
* Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
* All fertile males and females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end

Exclusion Criteria:

* Women with ongoing pregnancy or breast feeding
* Present therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to the first dose of study drug
* Any investigational drug 6 weeks prior to the first dose of study drug
* Co-infection with active hepatitis A, hepatitis B and/or human immunodeficiency virus (HIV)
* History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
* Clinical evidence of hepatocellular carcinoma
* History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
* Neutrophil count \<1500 cells/mm3 or platelet count \<90,000 cells/mm3 at screening
* Serum creatinine level \>1.5 times the upper limit of normal at screening
* History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease
* History of a severe seizure disorder or current anticonvulsant use
* History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
* History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
* Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
* Evidence of drug abuse (including excessive alcohol consumption\>40 g/day) within one year of study entry
* Inability or unwillingness to provide informed consent or abide by the requirements of the study
* Male partners of women who are pregnant
* Hgb \<11 g/dL in women or \<12 g/dL in men at screening
* Any patient with major thalassemia
* Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated

Primary outcomes:
measure: Efficacy: sustained virological response (SVR), HCV RNA seronegative by PCR throughout 24-week off-treatment period.
timeFrame: 1.5 years
Secondary outcomes:
measure: Rapid virologic response (RVR), HCV RNA seronegative by PCR at week 4.
timeFrame: 1.5 years
measure: Early virological response (EVR), by PCR-negative or at least 2 logs decline from baseline of serum HCV RNA at 12 weeks of treatment.
timeFrame: 1.5 years
measure: Safety: adverse event rate and profile.
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
Study officials:
affiliation: Kaohsiung Medical University
name: Wan-Long Chuang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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