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

Phase 2

Completed

• Conditions: Hepatocellular Carcinoma
• Interventions: Radiation: TACE+External beam RT; Drug: Sorafenib

• Registration Number: NCT01901692
• Lead Sponsor: Asan Medical Center

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2013-07-14
• Study First Submitted QC: 2013-07-14
• Study First Posted: 2013-07-17
• Study Start: 2013-07-29
• Primary Completion: 2017-01-20
• Study Completion: 2017-08-31
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-15
• Last Update Posted: 2017-09-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TACE+External beam RT	TACE+External beam RT	Transarterial chemoembolization plus external beam radiation therapy
Sorafenib	Sorafenib	Sorafenib 800 mg/day orally

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) rate	at 12 weeks after randomization	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.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) rate	at 24 weeks and up to 4 years after randomization	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.
Radiologic response rate	at 12 and 24 weeks after randomization	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.
treatment-crossover rate	at 12 and 24 weeks after randomization	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.
time to progression	up to 4 years after randomization	The median time to progression assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons.
Overall patient survival rate	up to 4 years after randomization	The median overall patient survival rate assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons.
Exploratory analysis for overall patient survival rate	up to 4 years after randomization	By using Cox proportional hazards model to evaluate the interaction between important baseline characteristics and the effect of treatments on overall survival.

Trial Locations

Locations (1)

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of