Sorafenib Monotherapy vs. TACE-sorafenib Sequential Therapy for HCC With Metastasis

Study Overview
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Brief Summary
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Sorafenib is the standard therapy for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, addition of transarterial chemoembolization (TACE) may be beneficial for controlling intrahepatic tumour. The investigators aimed to compare the efficacy between the sorafenib monotherapy and TACE-sorafenib sequential therapy in HCC patients with EHM.

Detailed Description
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Sorafenib is the standard therapy for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, transarterial chemoembolization (TACE) which is a standard therapy for intermediate stage may be beneficial for controlling intrahepatic tumour, thereby providing chance of improving survival in HCC patients with EHM. The investigators aimed to compare the efficacy between the sorafenib monotherapy and TACE-sorafenib sequential therapy in HCC patients with EHM. This study is a prospective randomized controlled study being conducted at 6 tertiary hospitals in South Korea. HCC patients with EHM are being enrolled and randomized into sorafenib monotherapy or TACE-sorafenib sequential therapy group. Patients with main portal vein invasion, Child-Pugh class B or C, and history of TACE or previous systemic therapy are being excluded. The sorafenib monotherapy group receives sorafenib immediately after randomization while the TACE-sorafenib group receives 2 4 times of TACE before starting sorafenib. Response evaluation are performed every 2 months, and time to progression (TTP), progression free survival (PFS), median survival time (MST), and overall survival (OS) which is the primary outcome measure will be compared.

Official Title
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Comparison of Efficacy Between Sorafenib Monotherapy vs. Transarterial Chemoembolization -Sorafenib Sequential Therapy in Hepatocellular Carcinoma Patients With Extrahepatic Metastasis

Conditions
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Hepatocellular Carcinoma, Metastasis

Intervention / Treatment
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* Procedure: transarterial chemoembolization (TACE)
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with hepatocellular carcinoma by the European Association for the Study of the Liver (EASL) criteria or pathology One or more extrahepatic metastatic lesion by proven radiologically or histologically No serious coagulation abnormalities Performance status 0 or 1 by Eastern Cooperative Oncology Group(ECOG) criteria Child-Pugh score 5 or 6 Serum creatinine <1.5mg/dL Age between 18   75 years old No other life-threatening medical illness Exclusion Criteria: Patients with main portal vein invasion Child-Pugh class B or C History of TACE or previous systemic chemotherapy including sorafenib Age >75 years old Cardiovascular diseases History of gastrointestinal bleeding within 2 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sorafenib monotherapy vs. transarterial chemoembolization-sorafenib sequential therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sorafenib monotherapy arm<br>The sorafenib monotherapy group receives sorafenib immediately after randomization. | Drug: Sorafenib<br>* Standard therapy for advanced HCC<br>|
| Experimental: TACE-sorafenib sequential therapy arm<br>TACE(transarterial chemoembolization )-sorafenib group receives 2 4 times of TACE before starting sorafenib. | Procedure: transarterial chemoembolization (TACE)<br>* Standard therapy for intermediate HCC, but nor for advanced HCC<br>Drug: Sorafenib<br>* Standard therapy for advanced HCC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Survival rate during the study period | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression (TTP) | Time form the enrollment to the event of progression | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years) | 
| Progression free survival (PFS) | Survival rate without progression of HCC | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years) | 
| Median survival time (MST) | Median time of the patient survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years) |