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

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
TACE+External beam RT
Sorafenib
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring liver cancer, first-line, tumor thrombus, vascular invasion

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Asan Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TACE+External beam RT

Sorafenib

Arm Description

Transarterial chemoembolization plus external beam radiation therapy

Sorafenib 800 mg/day orally

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
time to progression
The median time to progression assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons.
Overall patient survival rate
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
By using Cox proportional hazards model to evaluate the interaction between important baseline characteristics and the effect of treatments on overall survival.

Full Information

First Posted
July 14, 2013
Last Updated
September 15, 2017
Sponsor
Asan Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01901692
Brief Title
Sorafenib vs.TransArterial Chemoembolization Plus RadioTherapy in Hepatocellular Carcinoma With Macrovascular Invasion
Acronym
START
Official Title
Randomized Trial Comparing Sorafenib and Transarterial Chemoembolization Plus External Beam Radiotherapy in Patients With Hepatocellular Carcinoma Showing Macroscopic Vascular Invasion
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
July 29, 2013 (Actual)
Primary Completion Date
January 20, 2017 (Actual)
Study Completion Date
August 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
liver cancer, first-line, tumor thrombus, vascular invasion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TACE+External beam RT
Arm Type
Experimental
Arm Description
Transarterial chemoembolization plus external beam radiation therapy
Arm Title
Sorafenib
Arm Type
Active Comparator
Arm Description
Sorafenib 800 mg/day orally
Intervention Type
Radiation
Intervention Name(s)
TACE+External beam RT
Intervention Description
Trans-arterial chemoembolization (TACE) every 6 weeks + external beam radiation therapy starting within 3 weeks after first TACE
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Other Intervention Name(s)
Nexavar
Intervention Description
Sorafenib 800 mg/day orally
Primary Outcome Measure Information:
Title
Progression-free survival (PFS) rate
Description
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.
Time Frame
at 12 weeks after randomization
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS) rate
Description
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.
Time Frame
at 24 weeks and up to 4 years after randomization
Title
Radiologic response rate
Description
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.
Time Frame
at 12 and 24 weeks after randomization
Title
treatment-crossover rate
Description
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 Frame
at 12 and 24 weeks after randomization
Title
time to progression
Description
The median time to progression assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons.
Time Frame
up to 4 years after randomization
Title
Overall patient survival rate
Description
The median overall patient survival rate assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons.
Time Frame
up to 4 years after randomization
Title
Exploratory analysis for overall patient survival rate
Description
By using Cox proportional hazards model to evaluate the interaction between important baseline characteristics and the effect of treatments on overall survival.
Time Frame
up to 4 years after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Young-Suk Lim, MD, PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
29543938
Citation
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.
Results Reference
derived

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

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