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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sorafenib; Radiation: TACE+External beam RT

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Young-Suk Lim, MD, PhD, Asan Medical Center

Publications and helpful links

General Publications

• Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):661-669. doi: 10.1001/jamaoncol.2017.5847.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2013
• Primary Completion (Actual): January 20, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: July 14, 2013
• First Submitted That Met QC Criteria: July 14, 2013
• First Posted (Estimate): July 17, 2013

Study Record Updates

• Last Update Posted (Actual): September 18, 2017
• Last Update Submitted That Met QC Criteria: September 15, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: liver cancer; first-line; vascular invasion; tumor thrombus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: AMC IRB 2013-0627

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No