The Efficacy of 5-fluorouracil/Mitomycin for the Patients With Pulmonary Metastasis of Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The aim of this study is to evaluate the efficacy of 5-fluorouracil + Mitomycin for the patients with pulmonary metastasis of hepatocellular carcinoma who had progressive disease with sorafenib.

Detailed Description
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Extrahepatic metastasis of hepatocellular carcinoma has recently been paradoxically increasing due to increased survival with effective locoregional therapies. Sorafenib is the first systemic agent that has demonstrated a significant survival benefit in patients with advanced HCC; however, the modest improvement of 3 months is far from satisfactory. There is no convincing evidence, to date, that systemic chemotherapy when tumor progresses after sorafenib therapy improves overall survival. The combination of anticancer agents is important to achieve favourable clinical results. For patients with metastatic liver cancer or HCC, some studies have discussed the effectiveness of 5-fluorouracil/mitomycin(FM). However, few studies have examined the actual FM regimen for HCC. The aim of this study is to evaluate the efficacy of 5-fluorouracil/mitomycin for the patients with pulmonary metastasis of hepatocellular carcinoma who had progressive disease with sorafenib.

Official Title
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Phase II Study Evaluating the Efficacy of 5-fluorouracil/Mitomycin for the Patients With Pulmonary Metastasis of Hepatocellular Carcinoma Who Had Progressive Disease With Sorafenib

Conditions
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Hepatocellular Carcinoma, Lung Metastasis

Intervention / Treatment
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* Drug: 5-fluorouracil
* Drug: Mitomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have received previous local therapy treatments for the intrahepatic hepatocellular carcinoma (RFA, PEI, cryoablation, surgery, resection) and who don't have any viable intrahepatic tumor within 3 months of imaging (dynamic liver CT or liver MRI) after the locoregional therapy Patients who have measurable lung metastasis Patients who have received their last dose of sorafenib more than 14 days before and who had progressive disease of lung metastasis with sorafenib Patients who have risk factors of hepatocellular carcinoma (chronic hepatitis B, chronic hepatitis C, liver cirrhosis) Age : 18 years to 80 years ECOG Performance Status of 0 to 2 Child-Pugh class A,B (Child-Pugh score 5-9) Adequate bone marrow, liver function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: WBC count > 1,000/mm3 Absolute neutrophil count > 500/mm3 Hb > 7.0 g/dL Platelet count > 50,000 /mm3 Bilirubin < 3 mg/dL Adequate clotting function: INR < 2.3 or < 6sec Exclusion Criteria: Child-Pugh score > 10 ECOG Performance Status > 3 History of organ allograft Patients with uncontrolled co-morbidity which needs treatment Patients who have received prior systemic chemotherapy except sorafenib

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The 5-fluorouracil/mitomycin group<br>Systemic chemotherapy with 5-fluorouracil/mitomycin 5-fluorouracin 15mg/kg/day D1-6 civ + Mitomycin 4mg/day iv push D1,4 till progression, every 4 weeks | Drug: 5-fluorouracil<br>* 5-fluorouracin 15mg/kg/day D1-6 civ till progression, every 4 weeks<br>* Other names: 5-FU;Drug: Mitomycin<br>* Mitomycin 4mg/day iv push D1,4 till progression, every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-progression(TTP)of lung metastasis |  | every 12 weeks, up to 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | every 12 weeks, up to 36 weeks | 
| Response rates(CR + PR)of lung metastasis |  | every 12 weeks, up to 36 weeks | 
| progression free survival |  | every 12 weeks, up to 36 weeks | 
| Time to recurrence of intrahepatic tumor |  | every 12 weeks, up to 36 weeks | 
| Disease control rates (CR + PR + SD)of lung metastasis |  | every 12 weeks, up to 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, lung metastasis, 5-fluorouracil/mitomycin