Sorafenib Alone Versus Sorafenib Combined With HAIC for Advanced HCC

NCT ID: NCT02774187

Last Updated: 2019-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 247 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2018-08-31

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sorafenib combined with HAIC

Sorafenib combined with Hepatic arterial infusion chemotherapy with Folfox Protocol

Group Type: EXPERIMENTAL

Sorafenib

Intervention Type: DRUG

administration of Sorafenib

Hepatic arterial infusion chemotherapy

Intervention Type: PROCEDURE

administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries

Folfox Protocol

Intervention Type: DRUG

Oxaliplatin , fluorouracil, and leucovorin

Sorafenib alone

Sorafenib alone

Group Type: ACTIVE_COMPARATOR

Sorafenib

Intervention Type: DRUG

administration of Sorafenib

Interventions

Sorafenib

administration of Sorafenib

Intervention Type: DRUG

Hepatic arterial infusion chemotherapy

administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries

Intervention Type: PROCEDURE

Folfox Protocol

Oxaliplatin , fluorouracil, and leucovorin

Intervention Type: DRUG

Other Intervention Names

HAIC; Oxaliplatin , fluorouracil, and leucovorin

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Kaiping Central Hospital

OTHER

Sponsor Role: collaborator

Guangzhou No.12 People's Hospital

OTHER_GOV

Sponsor Role: collaborator

The First Affiliated Hospital of University of South China

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Shi Ming

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ming Shi, MD

Role: PRINCIPAL_INVESTIGATOR

The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center

Locations

Cancer Center Sun Yat-sen University

Guangzhou, Guangdong, China

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Guangzhou Twelfth People 's Hospita

Guangzhou, Guangdong, China

The Kaiping Center's Hospital

Kaiping, Guangdong, China

First Affiliated Hospital of University Of South China

Hengyang, Hunan, China

Countries

China

References

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.

Reference Type: RESULT

PMID: 12049862 (View on PubMed)

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.

Reference Type: RESULT

PMID: 11981766 (View on PubMed)

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.

Reference Type: RESULT

PMID: 12540794 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20839057 (View on PubMed)

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.

Reference Type: RESULT

PMID: 9149014 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20686792 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21514523 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25742141 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31070690 (View on PubMed)

Other Identifiers

HCC-S021

Identifier Type: -

Identifier Source: org_study_id