Clinical trial NCT03253250: The Investigation of Peginterferon Alfa-2a on the RFS of the Subjects With HCC Who Have Been Treated by Resection
Official title: A Prospective, Randomized, Multicenter, Open-label, Exploratory Study of Utilizing of Peginterferon Alfa-2a on the Relapse Rate of the Subjects With Hepatocellular Carcinoma Who Have Been Treated by Resection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis b
Hepatic Carcinoma
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2017-08-17
Enrollment: 432
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current study is a prospective, randomized, open, multi-center investigation. The aim of current study is to investigate whether the Recurrence-free Survival Rate (RFS）of the hepatitis B related -hepatocellular carcinoma subjects who have been treated by resection can be improved by peginterferon alfa-2a

Detailed description: The subjects who have been treated by resection due to hepatocellular carcinoma (HCC) will be randomized into 2 groups: the subjects in group A will be treated by Nucleotide analogues (NAs)( ETV, 0.5mg，qd；tenofovir disoproxil fumarate(TDF)，300mg，qd；ADV，10mg，qd）for 96 weeks; the subjects in group B will be treated by peginterferon alfa-2a （135μg/week）combination with NAs (ETV\\TDF\\ADV)for 96 weeks.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients with age ≥18 and ≤70 years;
2. Expected survival time \>3 months;
3. There should be evidences that chronic hepatitis B or hepatitis have been positive, hepatitis B virus (HBV) DNA detectable or undetectable, Alanine aminotransferase(ALT)\<upper limit of normal (ULN) or ≥ULN；
4. The patients have been treated by resection due to HCC;
5. The characteristic of tumor should be:Barcelona Clinic Liver Cancer(BCLC): 0,A,B
6. Child-Pugh scores:A
7. Agree to participate in the study and sign the patient informed consent form.

Exclusion Criteria:

1. Patients that have been treated by live transplantation、chemoembolization、radiotherapy、chemotherapy、molecular targeted therapy and biotherapy before the resection;
2. Patients that are treated by hepatotoxicity drugs 、immunosuppressant or adjuvant chemotherapy after the resection;
3. Patients who be treated by transcatheter arterial chemoembolization(TACE) after resection;
4. BCLC(Barcelona Clinic Liver Cancer):C、D before the resection;
5. History or other evidence of malignant tumor: except by basal cell carcinoma or squamous cell carcinoma which are cured 、carcinoma in situs of cervix
6. Allergic history to interferon;
7. Co-infection with active hepatitis A, hepatitis C, hepatitis D and/or human immunodeficiency virus (HIV);
8. History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);
9. absolute neutrophil count(ANC)\<1.5x 10\^9/L or platelet count(PLT)\<70x 10\^9/L
10. Creatinine over upper limit of normal;
11. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis that treated with antidepressant medication or a major tranquilizer at therapeutic doses respectively at any time prior to 3 months or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;
12. History of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases);
13. History of thyroid disease poorly controlled on prescribed medications;
14. Evidence of severe retinopathy or clinically relevant ophthalmologic disorder;
15. History of other severe disease or evidence of other severe disease or any other illness or conditions that the investigator believe that patients are not suitable to join in the study;
16. Evidence of postoperative complications: infectious、bleeding, etc,. at baseline; or evidence of recurrence or metastasis at baseline;
17. Child-Pugh scores :B、C
18. Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening;
19. Other disease should exclusive considered by the investigator.

Primary outcomes:
measure: Recurrence-free Survival Rate (RFS）
timeFrame: 2 years
Secondary outcomes:
measure: Recurrence-free Survival Rate (RFS）
timeFrame: 1 year
measure: Overall Survival Rate (OS）
timeFrame: 2 years
measure: Overall Survival Rate (OS）
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital
Study officials:
affiliation: Huashan Hospital
name: Lunxiu Qin
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Jimimg Zhang
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol. 2006 Jul;132(7):458-65. doi: 10.1007/s00432-006-0091-y. Epub 2006 Mar 24.
citation: Sohn W, Paik YH, Kim JM, Kwon CH, Joh JW, Cho JY, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. HBV DNA and HBsAg levels as risk predictors of early and late recurrence after curative resection of HBV-related hepatocellular carcinoma. Ann Surg Oncol. 2014 Jul;21(7):2429-35. doi: 10.1245/s10434-014-3621-x. Epub 2014 Mar 12.
citation: Micco L, Peppa D, Loggi E, Schurich A, Jefferson L, Cursaro C, Panno AM, Bernardi M, Brander C, Bihl F, Andreone P, Maini MK. Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B. J Hepatol. 2013 Feb;58(2):225-33. doi: 10.1016/j.jhep.2012.09.029. Epub 2012 Oct 6.