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

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.

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Interferon Alfa、Fluorouracil; Drug: Cisplatin、Fluorouracil

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 Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 565-0871
    • Recruiting
    • Osaka University, Graduate School of Medicine
    • Contact: Hiroshi Wada; Phone Number: +81-6-6879-3251

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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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.

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Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Interferon Alfa、Fluorouracil; 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; Other Names: Interferon Alfa ; IFN、; Fluorouracil ; 5-FU
Experimental: 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	Drug: Cisplatin、Fluorouracil; 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; Other Names: Fluorouracil ; 5-FU; Cisplatin ； Cispulan

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Kansai Hepatobiliary Oncology Group

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): February 1, 2018
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: April 16, 2013
• First Submitted That Met QC Criteria: April 16, 2013
• First Posted (Estimate): April 18, 2013

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: May 15, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Interferons; Interferon-alpha; Cisplatin; Fluorouracil
• Other Study ID Numbers: KHBO1207; UMIN000010425 (Registry Identifier: UMIN)