P2 Study of Postoperative Interferon/Fluorouracil vs Cisplatin/Fluorouracil for Hepatocellular Carcinoma.

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of postoperative hepatic arterial infusion chemotherapy, interferon/fluorouracil versus low-dose cisplatin/fluorouracil, in patients with hepatocellular carcinoma with portal vein tumor thrombus.

Detailed Description
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No standard treatment has been established for highly advanced hepatocellular carcinoma (HCC) invading the major branches of the portal vein except for sorafenib. Some reports suggested that hepatic arterial infusion chemotherapy improved survival of these patients. Other reports indicated surgical intervention improved that survival. However, there is no standard adjuvant therapy after liver resection for the patients with HCC with portal vein tumor thrombus in the main or first branch of the portal vein. Our preliminary results showed that combined interferon-alpha and intra-arterial 5-fluorouracil (5-FU) as a postoperative therapy prolonged disease-free and overall survival after liver resection. Hepatic arterial infusion chemotherapy using low-dose 5-FU and cisplatin is also promising regimen for advanced HCC. Herein, the investigators planed the study to evaluate efficacy (two year survival as primary outcome, and overall-survival as secondary outcome) and safety ( as secondary outcome) in hepatic arterial infusion chemotherapy with continuous infusion of 5-fluorouracil and systemic administration of interferon-alpha or low-dose 5-FU and cisplatin, and to compare the efficacy as randomized control trial.

Official Title
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Randomised Phase II Study of Postoperative Hepatic Arterial Infusion Chemotherapy (Interferon/Fluorouracil Versus Low-dose Cisplatin/Fluorouracil) for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus.

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Interferon Alfa、Fluorouracil
* Drug: Cisplatin、Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: hepatocellular carcinoma with histological or evidence or typical findings by CT or MRI. surgically resectable tumors with tumor thrombus in first branch or main trunk of portal vein. 20 years old or more. Eastern Cooperative Oncology Group Performance status of 0 or 1. Life expectancy of at least 6 months at the pre-treatment evaluation. Child-Pugh class A or B. Adequate bone marrow, liver and renal function, as assessed by the following laboratory requirements. white blood cell count >= 2000/microliter, Neutrophil >= 1000/microliter, Hemoglobin >= 9.0 g/dL, Platelet count >= 75000/microliter, Total Bilirubin <= 1.5mg/dl, aspartate aminotransferase(AST) /alanine aminotransferase(ALT) <= 150 IU/L, Serum creatinine <= 1.2mg/dL, Creatinine clearance >= 60 ml/min - Exclusion Criteria: Histological diagnosed combined hepatocellular and cholangiocellular carcinoma. Extrahepatic tumor spread which affects patient's prognosis. Hepatic encephalopathy Active infections except for hepatitis B virus(HBV) and hepatitis C virus(HCV). Sever complications (interstitial pneumonia, heart failure, renal failure, liver failure, ileus, incontrollable diabetes mellitus, and so on) Active double cancer Pregnancy 8-10) Medication or treatment that may affect to the absorption of drug or pharmacokinetics. 11) others, in the investigator's judgment. -

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interferon Alfa、Fluorouracil<br>Interferon Alfa 5×10⁶International Unit(IU)/body subcutaneously 3 times a week for 4 weeks Fluorouracil 300mg/m2, day1-5,8-12, every 6 weeks | Drug: Interferon Alfa、Fluorouracil<br>* Hepatic Arterial Infusion of 5-fluorouracil combined with systemic administration of Interferon-alpha Interferon Alfa 5×10⁶International Unit(IU)/body subcutaneously 3 times a week for 4 weeks Fluorouracil 300mg/m2, day1-5,8-12, every 6 weeks<br>* Other names: Fluorouracil ; 5-FU;|
| Experimental: Cisplatin、Fluorouracil<br>Cisplatin 20mg/m2 ,day1,8,22,29, every 6 weeks Fluorouracil 300mg/m2, day1-5,8-12,22-26,29-33, every 6 weeks | Drug: Cisplatin、Fluorouracil<br>* Hepatic Arterial Infusion of 5-fluorouracil and Cisplatin (Low-dose FP) Cisplatin 20mg/m2 ,day1,8,22,29, every 6 weeks Fluorouracil 300mg/m2, day1-5,8-12,22-26,29-33, every 6 weeks<br>* Other names: Fluorouracil ; 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two-year overall survival rate | Duration: From randomization to evidenced death. Rate: Number of patients with evidenced death / number of total patients. 2 year survival rate: survival rate at two-year from the randomization | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival time | Progression free survival time from randomization to tumor progression based on RECIST or recurrence after curative surgery was calculated by Kaplan Meier methods. | two years | 
| Overall survival time | Overall survival time from randomization to evidence death was calculated by Kaplan Meier methods. | two years | 
| toxicity | The incidence of adverse events evaluated by CTCAE Ver4.0. | At the end of hepatic arterial infusion chemotherapy (6 months) |