Sorafenib Alone Versus Sorafenib Combined With HAIC for Advanced HCC

• ClinicalTrials.gov Identifier: NCT02774187
• Recruitment Status: Completed
• First Posted: May 17, 2016
• Last Update Posted: December 5, 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
• Information provided by (Responsible Party): Shi Ming, Sun Yat-sen University

Tracking Information

• First Submitted Date: May 12, 2016
• First Posted Date: May 17, 2016
• Last Update Posted Date: December 5, 2019
• Actual Study Start Date: May 2016
• Actual Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 16, 2017)

Overall survival [ Time Frame: 6 months ]

Overall survival

• Original Primary Outcome Measures (submitted: May 12, 2016): Overall survival [ Time Frame: 6 months ]

Current Secondary Outcome Measures (submitted: October 16, 2017)

• Time to progression [ Time Frame: 6 months ]
  Time to progression
• Adverse Events [ Time Frame: 30 days ]
  Number of adverse events. Postoperative adverse events were graded based on CTCAE v3.0
• Number of of Patients developed Adverse Events [ Time Frame: 30 days ]
  Number of of patients who developed adverse event. Postoperative adverse events were graded based on CTCAE v3.0

Original Secondary Outcome Measures (submitted: May 12, 2016)

• Time to progression [ Time Frame: 6 months ]
• Adverse Events [ Time Frame: 30 days ]
  Number of adverse events. Postoperative adverse events were graded based on CTCAE v3.0
• Number of of Patients developed Adverse Events [ Time Frame: 30 days ]
  Number of of patients who developed adverse event. Postoperative adverse events were graded based on CTCAE v3.0

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma

Intervention

• Drug: Sorafenib
  administration of Sorafenib
• Procedure: Hepatic arterial infusion chemotherapy
  administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries
  Other Name: HAIC
• Drug: Folfox Protocol
  Oxaliplatin , fluorouracil, and leucovorin
  Other Name: Oxaliplatin , fluorouracil, and leucovorin

Study Arms

• Experimental: Sorafenib combined with HAIC
  Sorafenib combined with Hepatic arterial infusion chemotherapy with Folfox Protocol
  Interventions:

  • Drug: Sorafenib
  • Procedure: Hepatic arterial infusion chemotherapy
  • Drug: Folfox Protocol
• Active Comparator: Sorafenib alone
  Sorafenib alone
  Intervention: Drug: Sorafenib

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 3, 2018): 247
• Original Estimated Enrollment (submitted: May 12, 2016): 162
• Actual Study Completion Date: August 2018
• Actual Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02774187
• Other Study ID Numbers: HCC-S021
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Shi Ming, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current

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

Investigators

• Principal Investigator: Ming Shi, MD; The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center

• PRS Account: Sun Yat-sen University
• Verification Date: December 2019