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

Information source: Seoul National University Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Carcinoma, Hepatocellular

Intervention: 5-FU (Drug); Mitomycin (Drug); sorafenib (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Seoul National University Hospital

Official(s) and/or principal investigator(s):
Jung-Hwan Yoon, M.D., Ph.D., Principal Investigator, Affiliation: Seoul National University Hospital

Overall contact:
Jung-Hwan Yoon, Phone: +82-2-2072-2731, Email: yoonjh@snu.ac.kr


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.

Clinical Details

Official title: An Open Label, Phase 2 Trial Comparing Sorafenib and 5-fluorouracil/Mitomycin in Hepatocellular Carcinoma With Pulmonary Metastasis

Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Progression free survival (PFS)

Secondary outcome:

Time-to-progression (TTP)

Objective tumor response rate

Adverse event rates and the toxicities

Overall survival

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. Outline:

- 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.


Minimum age: 20 Years. Maximum age: 80 Years. Gender(s): Both.


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)

Locations and Contacts

Jung-Hwan Yoon, Phone: +82-2-2072-2731, Email: yoonjh@snu.ac.kr

Seoul National University Hospital, Seoul, Korea, Republic of; Recruiting
Additional Information

Starting date: November 2010
Last updated: November 26, 2014

Page last updated: August 23, 2015

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