Sorafenib vs.TransArterial Chemoembolization Plus RadioTherapy in Hepatocellular Carcinoma With Macrovascular Invasion

Study Overview
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Brief Summary
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To evaluate and compare the efficacy and safety of sorafenib versus trans-arterial chemoembolization plus external beam radiation therapy in patients with hepatocellular carcinoma invading major intrahepatic vessels

Detailed Description
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Current practice guidelines recommend only sorafenib for patients with hepatocellular carcinoma invading major intrahepatic vessels. However, recent data from observational studies suggest that the combination of transarterial chemoembolization and external beam radiotherapy would be as effective as sorafenib.

Official Title
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Randomized Trial Comparing Sorafenib and Transarterial Chemoembolization Plus External Beam Radiotherapy in Patients With Hepatocellular Carcinoma Showing Macroscopic Vascular Invasion

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Radiation: TACE+External beam RT
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >19 years Child-Pugh class A liver function Performance status: Eastern Cooperative Oncology Group (ECOG) score 0 or 1 Hepatocellular carcinoma (HCC) confirmed by dynamic CT or MRI, or by biopsy HCC invasion of first or second branch portal vein or hepatic vein or inferior vena cava Reserved unilateral portal blood flow at least in partial HCC size larger than 1 cm and less than 50% of total liver volume No confirmed extrahepatic metastasis Adequate hematopoietic function Hemoglobin ≥ 8.5 g/dL Absolute neutrophil count ≥ 750/mm3 Platelet count ≥ 30,000/mm3 Creatinine < 1.5mg/dL No plan for pregnancy or breast feeding. Active contraception. Willing to give informed consent Exclusion Criteria: Prior history to or exposure of transarterial chemoembolization, external beam radiation to liver, or sorafenib Complete obstruction of hepatic outflow Confirmed extrahepatic metastasis of HCC HCC occupying more than 50% of liver volume Uncontrolled ascites of hepatic encephalopathy Prior liver transplantation Positive for human immunodeficiency virus (HIV) Active gastric or duodenal ulcer Other uncontrolled comorbidities or malignancy Inability to give informed consent

Ages Eligible for Study
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Minimum Age: 20 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TACE+External beam RT<br>Transarterial chemoembolization plus external beam radiation therapy | Radiation: TACE+External beam RT<br>* Trans-arterial chemoembolization (TACE) every 6 weeks + external beam radiation therapy starting within 3 weeks after first TACE<br>|
| Active Comparator: Sorafenib<br>Sorafenib 800 mg/day orally | Drug: Sorafenib<br>* Sorafenib 800 mg/day orally<br>* Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) rate | Progression is defined as progressive disease (PD) by independent radiologic review according to RECIST criteria (version 1.1), termination of the assigned treatment, or death from any cause, assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons with the intention-to-treat principle. | at 12 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) rate | Progression is defined as progressive disease (PD) by independent radiologic review according to RECIST criteria (version 1.1), termination of the assigned treatment, or death from any cause, assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. | at 24 weeks and up to 4 years after randomization | 
| Radiologic response rate | Radiologic response rate by independent radiologic review according to RECIST criteria (version 1.1), , assessed by Chi-square test or Fisher's exact test, as appropriate. | at 12 and 24 weeks after randomization | 
| treatment-crossover rate | Crossover of treatment is permitted after confirming the disease progression during the initially assigned treatment, assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. | at 12 and 24 weeks after randomization | 
| time to progression | The median time to progression assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. | up to 4 years after randomization | 
| Overall patient survival rate | The median overall patient survival rate assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. | up to 4 years after randomization | 
| Exploratory analysis for overall patient survival rate | By using Cox proportional hazards model to evaluate the interaction between important baseline characteristics and the effect of treatments on overall survival. | up to 4 years after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cancer, first-line, tumor thrombus, vascular invasion