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

Phase 2

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: Interferon Alfa、Fluorouracil; Drug: Cisplatin、Fluorouracil

• Registration Number: NCT01834963
• Lead Sponsor: Kansai Hepatobiliary Oncology Group

Brief Summary

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

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.

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-04-16
• Study First Submitted QC: 2013-04-16
• Study First Posted: 2013-04-18
• Status Verified: 2017-08
• Primary Completion: 2018-02
• Last Update Submitted: 2018-05-15
• Last Update Posted: 2018-05-18
• Study Completion: 2020-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. hepatocellular carcinoma with histological or evidence or typical findings by CT or MRI.
2. surgically resectable tumors with tumor thrombus in first branch or main trunk of portal vein.
3. 20 years old or more.
4. Eastern Cooperative Oncology Group Performance status of 0 or 1.
5. Life expectancy of at least 6 months at the pre-treatment evaluation.
6. Child-Pugh class A or B.
7. 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

1. Histological diagnosed combined hepatocellular and cholangiocellular carcinoma.
2. Extrahepatic tumor spread which affects patient's prognosis.
3. Hepatic encephalopathy
4. Active infections except for hepatitis B virus(HBV) and hepatitis C virus(HCV).
5. Sever complications (interstitial pneumonia, heart failure, renal failure, liver failure, ileus, incontrollable diabetes mellitus, and so on)
6. Active double cancer
7. Pregnancy 8-10) Medication or treatment that may affect to the absorption of drug or pharmacokinetics.

11. others, in the investigator's judgment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Interferon Alfa、Fluorouracil	Interferon Alfa、Fluorouracil	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
Cisplatin、Fluorouracil	Cisplatin、Fluorouracil	Cisplatin 20mg/m2 ,day1,8,22,29, every 6 weeks Fluorouracil 300mg/m2, day1-5,8-12,22-26,29-33, every 6 weeks

Primary Outcome Measures

Name	Time	Method
Two-year overall survival rate	Two years	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Osaka University, Graduate School of Medicine; 🇯🇵 Osaka, Japan