Efficacy and Safety of Concurrent TACE and Sorafenib in Patients With HCC and Extrahepatic Metastasis (COTSOM Study)

NCT02311205 | Unknown Phase 2

• 1 other identifier: 2014-0902
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase II, prospective, open-label, single arm, single center study of the efficacy and safety of concurrent conventional transarterial chemoembolization (TACE) and sorafenib in patients with hepatocellular carcinoma and extrahepatic metastasis. All of the 55 patients with hepatocellular carcinoma and newly diagnosed extrahepatic (lung, bone, lymph node, adrenal gland) metastasis will be included. On demand conventional TACE will be performed in all the patients after enrollment and can be continued until intrahepatic CR, TACE failure or consent withdrawal. Sorafenib will be started 3-7 days after the first and each subsequent TACE and stopped one day before next TACE and will be continued until sorafenib failure, consent withdrawal or condition worsening by clinical decision. Repeated on-demand TACE and sorafenib should continue until the criteria for treatment discontinuation are met. After initiation of sorafenib combination treatment, patients will be seen and will perform routine examination at week 4 and, after then routine examination will be followed every 6 ± 2 weeks.

Conditions

Hepatocellular Carcinoma; Metastasis

Keywords

Transarterial Chemoembolization (TACE); Hepatocellular carcinoma (HCC); Metastasis; Sorafenib

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Overall survival (OS) from the start of first TACE as a part of combination treatment

  Up to 1 year from the start of first TACE as a part of combination treatment

Secondary Outcomes (7)

• Safety (adverse events and laboratory values)

  Up to 1 year from the start of first TACE as a part of combination treatment

• Liver dysfunction (laboratory values related to liver)

  Up to 1 year from the start of first TACE as a part of combination treatment

• Time to progression (TTP)

  Up to 1 year from the start of first TACE as a part of combination treatment

• Time to TACE failure (TTTF)

  Up to 1 year from the start of first TACE as a part of combination treatment

• Time to sorafenib failure (TTSF)

  Up to 1 year from the start of first TACE as a part of combination treatment

Study Arms (1)

TACE+sorafenib

EXPERIMENTAL

Concurrent Conventional Transarterial Chemoembolization (TACE) and Sorafenib

Procedure: Conventional Transarterial Chemoembolization (TACE); Drug: sorafenib

Interventions

Conventional Transarterial Chemoembolization (TACE) PROCEDURE

On demand conventional TACE will be performed in all the patients after enrollment and can be continued until intrahepatic CR, TACE failure or consent withdrawal. Sorafenib will be started 3-7 days after the first and each subsequent TACE and stopped one day before next TACE and will be continued until sorafenib failure, consent withdrawal or condition worsening by clinical decision.

TACE+sorafenib

sorafenib DRUG

Sorafenib will be started 3-7 days after the first and each subsequent TACE and stopped one day before next TACE and will be continued until sorafenib failure, consent withdrawal or condition worsening by clinical decision.

Also known as: nexavar

TACE+sorafenib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with HCC and newly diagnosed extrahepatic metastasis meeting of following criteria
• Clinical or histological diagnosis of HCC based on the guidelines: Early enhancement followed by late wash-out on dynamic liver imaging (CT or MRI) Or Pathological examination of liver biopsy
• Evidence of extrahepatic metastasis with any of following methods; CT, MRI, bone scan, positron emission tomography with FDG-PET, biopsy of metastatic lesion
• Preserved liver function classified as Child-Pugh A
• ECOG PS of 0-1
• Age of at least 20 years
• Patients is able to comply with scheduled visits, evaluation plan, and other study procedures
• Patient is willing to provide written informed consent
• There is no limitation of prior TACE session number in case that further TACE is still considered to be beneficial
• Women of childbearing potential must have a negative pregnancy test performed within 14 days of the start of treatment. All patients of child-bearing potential must use adequate birth control measures during the course of the trial (barrier method of birth control) and up to at least 30 days of last dose.

You may not qualify if:

• Presence of any of following criteria
• Patients who are diagnosed as not eligible for further TACE before screening
• Patients with advanced liver disease as defined below:
• Child Pugh B and C
• Encephalopathy
• Ascites
• Complete occlusion of main portal vein (PV) by HCC
• Patients with brain metastasis
• Inadequate liver function that could not perform TACE:
• AST \> 5 X ULN(upper limit normal) or ALT \> 5 X ULN
• Total bilirubin \> 2.0 mg/dL
• Prothrombin time INR \> 1.7
• Inadequate bone marrow function (absolute neutrophil count \< 1,500/μL, Hemoglobin (Hgb) \< 8 g/dL, platelet count \< 50,000/μL)
• Inadequate renal function (creatinine \> 1.5 x ULN)
• Treatment with previous local therapy such as resection of HCC, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) \< 4 weeks prior to the screening

Sponsors & Collaborators

• Asan Medical Center: lead
• Bayer: collaborator

Study Sites (1)

Asan Medical Center

Seoul, South Korea

Location

Related Publications (7)

• Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005 Nov;42(5):1208-36. doi: 10.1002/hep.20933. No abstract available.

  PMID: 16250051 BACKGROUND

• Pang RW, Poon RT. From molecular biology to targeted therapies for hepatocellular carcinoma: the future is now. Oncology. 2007;72 Suppl 1:30-44. doi: 10.1159/000111705. Epub 2007 Dec 13.

  PMID: 18087180 BACKGROUND

• Kim KM, Kim JH, Park IS, Ko GY, Yoon HK, Sung KB, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion. J Gastroenterol Hepatol. 2009 May;24(5):806-14. doi: 10.1111/j.1440-1746.2008.05728.x. Epub 2009 Jan 13.

  PMID: 19207681 BACKGROUND

• Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, Kojiro M, Makuuchi M; HCC Expert Panel of Japan Society of Hepatology. Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011;29(3):339-64. doi: 10.1159/000327577. Epub 2011 Aug 9.

  PMID: 21829027 BACKGROUND

• Yoo DJ, Kim KM, Jin YJ, Shim JH, Ko GY, Yoon HK, Sung KB, Lee JL, Kang YK, Lim YS, Lee HC, Chung YH, Lee YS, Suh DJ. Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: does transarterial chemoembolization improve survival in these patients? J Gastroenterol Hepatol. 2011 Jan;26(1):145-54. doi: 10.1111/j.1440-1746.2010.06341.x.

  PMID: 21175808 BACKGROUND

• Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

  PMID: 18650514 BACKGROUND

• Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010 Feb;30(1):52-60. doi: 10.1055/s-0030-1247132. Epub 2010 Feb 19.

  PMID: 20175033 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasm Metastasis

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Kang Mo Kim, MD, PhD

  Asan Medical Center, University of Ulsan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: December 8, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: June 1, 2018
• Last Updated: December 18, 2017

Record last verified: 2017-12

Locations

KR (1)