Comparison Study of Sorafenib and 5-fluorouracil/Mitomycin for Metastatic Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01171482
Recruitment Status : Terminated (There were problems with national reimbursement policies.)
First Posted : July 28, 2010
Last Update Posted : April 26, 2017
Information provided by (Responsible Party):
Jung-Hwan Yoon, Seoul National University Hospital

Brief Summary:
The aim of this study is to compare the efficacy of sorafenib to 5-fluorouracil/mitomycin in HCC patients with pulmonary metastasis whose intrahepatic tumors has been controlled with locoregional therapies.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: 5-FU Drug: Mitomycin Drug: sorafenib Phase 2

Detailed Description:

Most HCC patients are diagnosed at advanced stages in Korea, but effective treatment strategies for advanced HCC have not been established. In particular, optimal treatment strategy for extrahepatic as well as intrahepatic recurrences following locoregional therapy (e.g., transarterial chemoembolization, radiofrequency ablation therapy, and percutaneous ethanol injection) is still a challenging issue. Extrahepatic metastasis has been encountered more frequently, being more problematic than before in the management of HCC due to the increased survival with effective locoregional treatments. The lung is the most common site of extrahepatic metastasis and the surgical resection of pulmonary metastatic lesions may result in improved survival in selected patients. Previous studies suggested that aggressive management including resection of the extrahepatic recurrence combined with locoregional therapy for intrahepatic HCC may offer long-term survival in selected patients with recurrent HCC following hepatectomy. Such an aggressive strategy has serious limitation in clinical practice in that extrahepatic recurrence usually present as multiple lesions. Systemic chemotherapy has been one of the most commonly used treatment modalities for patients with multiple extrahepatic metastasis. However, chemotherapy using either a single or combined cytotoxic agents provides only limited benefit for such patients. The aim of this study is to compare the efficacy of sorafenib to 5-fluorouracil/mitomycin in HCC patients with pulmonary metastasis whose intrahepatic tumors had been previously controlled with repeated locoregional therapies before the initiation of systemic chemotherapy.


  • Experimental arm(the FM group): Patients receive 5-FU IV continuously over 10 hours on day 1~6 and mitomycin IV push on day 1~4. Treatment repeats every 28 days.
  • Active Comparator arm(the sorafenib group): Patients will receive 2 tablets of sorafenib (200 mg/tablet) twice daily, orally on a continuous basis.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. During the treatment period, patients will have study visits on Day 1 of every cycle (every 4 weeks from start of study drug) and will receive CT/MRI assessment every 2 cycles (every 8 weeks). In the event of radiological progression confined to the liver, e.g. appearance of new nodules in the liver in areas previously not treated by locoregional therapies, patients will then also be treated with locoregional therapies such as TACE or local ablation as long as the they may still benefit from treatment. If patients are no longer amenable to locoregional therapies (in the case of untreatable progression), the study will be stopped and best supportive care be offered. This will be based on the investigator's clinical judgment of the subject's status.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Phase 2 Trial Comparing Sorafenib and 5-fluorouracil/Mitomycin in Hepatocellular Carcinoma With Pulmonary Metastasis
Study Start Date : November 2015
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: The FM group
Patients in the FM group will be administered 5-FU plus mitomycin
Drug: 5-FU
15mg/kg/day continuous IV from day 1 to day 6 every 28 days.
Other Name: 5-fluorouracil

Drug: Mitomycin
4mg/day IV push from day 1 to day 4 every 28 days

Active Comparator: The sorafenib group
Patients in the sorafenib group will be administered sorafenib
Drug: sorafenib
400 mg BID every 28 days
Other Name: Nexavar

Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: every 8 weeks ]

Secondary Outcome Measures :
  1. Time-to-progression (TTP) [ Time Frame: every 8 weeks ]
  2. Objective tumor response rate [ Time Frame: Determined by CT scan at the end of every 2 cycles until progressive disease is documented or intolerable toxicity occurs ]
  3. Adverse event rates and the toxicities [ Time Frame: every 4 weeks ]
  4. Overall survival [ Time Frame: every 8 weeks ]

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with clinical or histological diagnosis of HCC based on the guidelines of the AJCC
  • Patients with at least one, bi-dimensionally measurable, pulmonary metastasis without intrahepatic viable tumor (Viable tumor is defined as uptake of contrast agent in the arterial phase of dynamic CT or MRI.)
  • Patients who have received previous local therapy treatments (RFA, PEI, cryoablation, surgery, resection) to non-target lesions are eligible
  • Age : 20 years to 80 years
  • ECOG Performance Status of 0 to 1
  • Child-Pugh class A or B (Child-Pugh score 7)
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

    • Hb ≧ 9 g/dL
    • Absolute neutrophil count > 1000/mm3
    • Platelet count ≧ 60,000 /mm3
    • Adequate clotting function: INR < 1.5
    • Hepatic: AST and ALT < 5 X ULN
    • Renal: serum creatinine < 1.7mg/dL
    • Bilirubin ≦ 3 mg/dL

Exclusion Criteria:

  • Patients with diffuse infiltrative type of HCC that are poorly defined
  • Presence of hepatic encephalopathy and intractable ascites
  • Patients who are on a liver transplant list
  • The patient has received prior systemic chemotherapy
  • History of organ allograft
  • Active clinically serious infections (> grade 2 NCI-CTC version 3.0), including spontaneous bacterial peritonitis
  • History of cardiac disease: congestive heart failure > NYHA class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed), cardiac arrhythmias requiring anti-arrhythmic therapy or uncontrolled hypertension and diabetes mellitus
  • Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted
  • HIV infection or AIDS-related illness or serious acute or chronic illness (based on medical history)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01171482

Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Seoul National University Hospital
Principal Investigator: Jung-Hwan Yoon, M.D., Ph.D. Seoul National University Hospital

Responsible Party: Jung-Hwan Yoon, Professor, Seoul National University Hospital Identifier: NCT01171482     History of Changes
Other Study ID Numbers: 07-2010-010
First Posted: July 28, 2010    Key Record Dates
Last Update Posted: April 26, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Vitamin B Complex
Growth Substances
Antibiotics, Antineoplastic