Sorafenib Alone Versus Sorafenib Combined With HAIC for Advanced HCC
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Sorafenib
Hepatic arterial infusion chemotherapy
Folfox Protocol
Sponsored by

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, Hepatic arterial infusion chemotherapy, Sorafenib
Eligibility Criteria
Inclusion Criteria:
- The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
- Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
- portal vein tumor thrumbus confirmed in two image techniques
- Eastern Cooperative Oncology Group performance status of 0 to 2
- with no previous treatment
- No Cirrhosis or cirrhotic status of Child-Pugh class A only
- Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
The following laboratory parameters:
- Platelet count ≥ 75,000/µL
- Hemoglobin ≥ 8.5 g/dL
- Total bilirubin ≤ 30mmol/L
- Serum albumin ≥ 30 g/L
- ASL and AST ≤ 5 x upper limit of normal
- Serum creatinine ≤ 1.5 x upper limit of normal
- INR ≤ 1.5 or PT/APTT within normal limits
- Absolute neutrophil count (ANC) >1,500/mm3
- Ability to understand the protocol and to agree to and sign a written informed consent document
Exclusion Criteria:
- Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
- Known history of HIV
- History of organ allograft
- Known or suspected allergy to the investigational agents or any agent given in association with this trial.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Evidence of bleeding diathesis.
- Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
- Known central nervous system tumors including metastatic brain disease
Sites / Locations
- Cancer Center Sun Yat-sen University
- The First Affiliated Hospital of Sun Yat-sen University
- Guangzhou Twelfth People 's Hospita
- The Kaiping Center's Hospital
- First Affiliated Hospital of University Of South China
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Sorafenib combined with HAIC
Sorafenib alone
Arm Description
Sorafenib combined with Hepatic arterial infusion chemotherapy with Folfox Protocol
Sorafenib alone
Outcomes
Primary Outcome Measures
Overall survival
Overall survival
Secondary Outcome Measures
Time to progression
Time to progression
Adverse Events
Number of adverse events. Postoperative adverse events were graded based on CTCAE v3.0
Number of of Patients developed Adverse Events
Number of of patients who developed adverse event. Postoperative adverse events were graded based on CTCAE v3.0
Full Information
NCT ID
NCT02774187
First Posted
May 12, 2016
Last Updated
December 3, 2019
Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Kaiping Central Hospital, Guangzhou No.12 People's Hospital, The First Affiliated Hospital of University of South China
1. Study Identification
Unique Protocol Identification Number
NCT02774187
Brief Title
Sorafenib Alone Versus Sorafenib Combined With HAIC for Advanced HCC
Official Title
Sorafenib Alone Versus Sorafenib Combined With Hepatic Arterial Chemoinfusion for Advanced HCC With Portal Vein Tumor Thrombosis: a Multicentre Randomised Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
August 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Kaiping Central Hospital, Guangzhou No.12 People's Hospital, The First Affiliated Hospital of University of South China
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of sorafenib combined with hepatic arterial infusion chemotherapy (HAIC) compared with sorafenib Alone in patients with hepatocellular carcinoma (HCC) with major portal venous tumor thrombus (PVTT).
Detailed Description
The results of our preliminary pilot study suggested that sorafenib combined with hepatic arterial infusion chemotherapy (HAIC) may improve the survivals for advanced stage HCC. Thus, the investigators carried out this prospective randomized control study to find out it.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular Carcinoma, Hepatic arterial infusion chemotherapy, Sorafenib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
247 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib combined with HAIC
Arm Type
Experimental
Arm Description
Sorafenib combined with Hepatic arterial infusion chemotherapy with Folfox Protocol
Arm Title
Sorafenib alone
Arm Type
Active Comparator
Arm Description
Sorafenib alone
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
administration of Sorafenib
Intervention Type
Procedure
Intervention Name(s)
Hepatic arterial infusion chemotherapy
Other Intervention Name(s)
HAIC
Intervention Description
administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries
Intervention Type
Drug
Intervention Name(s)
Folfox Protocol
Other Intervention Name(s)
Oxaliplatin , fluorouracil, and leucovorin
Intervention Description
Oxaliplatin , fluorouracil, and leucovorin
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Time to progression
Description
Time to progression
Time Frame
6 months
Title
Adverse Events
Description
Number of adverse events. Postoperative adverse events were graded based on CTCAE v3.0
Time Frame
30 days
Title
Number of of Patients developed Adverse Events
Description
Number of of patients who developed adverse event. Postoperative adverse events were graded based on CTCAE v3.0
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
portal vein tumor thrumbus confirmed in two image techniques
Eastern Cooperative Oncology Group performance status of 0 to 2
with no previous treatment
No Cirrhosis or cirrhotic status of Child-Pugh class A only
Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
The following laboratory parameters:
Platelet count ≥ 75,000/µL
Hemoglobin ≥ 8.5 g/dL
Total bilirubin ≤ 30mmol/L
Serum albumin ≥ 30 g/L
ASL and AST ≤ 5 x upper limit of normal
Serum creatinine ≤ 1.5 x upper limit of normal
INR ≤ 1.5 or PT/APTT within normal limits
Absolute neutrophil count (ANC) >1,500/mm3
Ability to understand the protocol and to agree to and sign a written informed consent document
Exclusion Criteria:
Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
Known history of HIV
History of organ allograft
Known or suspected allergy to the investigational agents or any agent given in association with this trial.
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
Evidence of bleeding diathesis.
Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
Known central nervous system tumors including metastatic brain disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ming Shi, MD
Organizational Affiliation
The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Center Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
The First Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
Guangzhou Twelfth People 's Hospita
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510620
Country
China
Facility Name
The Kaiping Center's Hospital
City
Kaiping
State/Province
Guangdong
ZIP/Postal Code
529300
Country
China
Facility Name
First Affiliated Hospital of University Of South China
City
Hengyang
State/Province
Hunan
ZIP/Postal Code
421001
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
12049862
Citation
Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. doi: 10.1016/S0140-6736(02)08649-X.
Results Reference
result
PubMed Identifier
11981766
Citation
Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71. doi: 10.1053/jhep.2002.33156.
Results Reference
result
PubMed Identifier
12540794
Citation
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003 Feb;37(2):429-42. doi: 10.1053/jhep.2003.50047.
Results Reference
result
PubMed Identifier
20839057
Citation
Luo J, Guo RP, Lai EC, Zhang YJ, Lau WY, Chen MS, Shi M. Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol. 2011 Feb;18(2):413-20. doi: 10.1245/s10434-010-1321-8. Epub 2010 Sep 14.
Results Reference
result
PubMed Identifier
9149014
Citation
Ando E, Yamashita F, Tanaka M, Tanikawa K. A novel chemotherapy for advanced hepatocellular carcinoma with tumor thrombosis of the main trunk of the portal vein. Cancer. 1997 May 15;79(10):1890-6. doi: 10.1002/(sici)1097-0142(19970515)79:103.0.co;2-k.
Results Reference
result
PubMed Identifier
20686792
Citation
Shi J, Lai EC, Li N, Guo WX, Xue J, Lau WY, Wu MC, Cheng SQ. A new classification for hepatocellular carcinoma with portal vein tumor thrombus. J Hepatobiliary Pancreat Sci. 2011 Jan;18(1):74-80. doi: 10.1007/s00534-010-0314-0.
Results Reference
result
PubMed Identifier
21514523
Citation
Huang ZL, Luo J, Chen MS, Li JQ, Shi M. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization. J Vasc Interv Radiol. 2011 May;22(5):702-9. doi: 10.1016/j.jvir.2010.12.041.
Results Reference
result
PubMed Identifier
25742141
Citation
Fan W, Zhang Y, Wang Y, Yao X, Yang J, Li J. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of survival and metastasis for recurrent hepatocellular carcinoma after transarterial chemoembolization. PLoS One. 2015 Mar 5;10(3):e0119312. doi: 10.1371/journal.pone.0119312. eCollection 2015.
Results Reference
result
PubMed Identifier
31070690
Citation
He M, Li Q, Zou R, Shen J, Fang W, Tan G, Zhou Y, Wu X, Xu L, Wei W, Le Y, Zhou Z, Zhao M, Guo Y, Guo R, Chen M, Shi M. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):953-960. doi: 10.1001/jamaoncol.2019.0250.
Results Reference
derived
Learn more about this trial
Sorafenib Alone Versus Sorafenib Combined With HAIC for Advanced HCC
We'll reach out to this number within 24 hrs