Sorafenib Monotherapy vs. TACE-sorafenib Sequential Therapy for HCC With Metastasis

Hepatocellular Carcinoma Clinical Trial

Official title:

Comparison of Efficacy Between Sorafenib Monotherapy vs. Transarterial Chemoembolization -Sorafenib Sequential Therapy in Hepatocellular Carcinoma Patients With Extrahepatic Metastasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03518502
• Other study ID #: 2012AS0313
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2012
• Est. completion date: February 28, 2022

Study information

• Verified date: May 2018
• Source: Korea University
• Contact: Hyung Joon Yim, M.D.
• Phone: 82-31-412-6565
• Email: gudwns21[@]korea.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sorafenib is the standard therapy for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, addition of transarterial chemoembolization (TACE) may be beneficial for controlling intrahepatic tumour. The investigators aimed to compare the efficacy between the sorafenib monotherapy and TACE-sorafenib sequential therapy in HCC patients with EHM.

Description:

Sorafenib is the standard therapy for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, transarterial chemoembolization (TACE) which is a standard therapy for intermediate stage may be beneficial for controlling intrahepatic tumour, thereby providing chance of improving survival in HCC patients with EHM.

The investigators aimed to compare the efficacy between the sorafenib monotherapy and TACE-sorafenib sequential therapy in HCC patients with EHM.

This study is a prospective randomized controlled study being conducted at 6 tertiary hospitals in South Korea. HCC patients with EHM are being enrolled and randomized into sorafenib monotherapy or TACE-sorafenib sequential therapy group. Patients with main portal vein invasion, Child-Pugh class B or C, and history of TACE or previous systemic therapy are being excluded. The sorafenib monotherapy group receives sorafenib immediately after randomization while the TACE-sorafenib group receives 2~4 times of TACE before starting sorafenib. Response evaluation are performed every 2 months, and time to progression (TTP), progression free survival (PFS), median survival time (MST), and overall survival (OS) which is the primary outcome measure will be compared.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: February 28, 2022
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with hepatocellular carcinoma by the European Association for the Study of the Liver (EASL) criteria or pathology

• One or more extrahepatic metastatic lesion by proven radiologically or histologically

• No serious coagulation abnormalities

• Performance status 0 or 1 by Eastern Cooperative Oncology Group(ECOG) criteria

• Child-Pugh score 5 or 6

• Serum creatinine <1.5mg/dL

• Age between 18 ~ 75 years old

• No other life-threatening medical illness

Exclusion Criteria:

• Patients with main portal vein invasion

• Child-Pugh class B or C

• History of TACE or previous systemic chemotherapy including sorafenib

• Age >75 years old

• Cardiovascular diseases

• History of gastrointestinal bleeding within 2 weeks

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Metastasis
• Neoplasm Metastasis

Intervention

Procedure:
• transarterial chemoembolization (TACE)
Standard therapy for intermediate HCC, but nor for advanced HCC

Drug:
• Sorafenib
Standard therapy for advanced HCC

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan	Gyeonggi-do
Korea, Republic of	Soonchunghyang University Bucheon Hospital	Bucheon	Gyeonggi-do
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Chonnam National University Hwasoon Hospital	Gwangju
Korea, Republic of	Seoul Saint Marry Hospital, the Catholic University of Korea	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Korea University	Korean Liver Cancer Study Group

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (7)

Cabrera R, Pannu DS, Caridi J, Firpi RJ, Soldevila-Pico C, Morelli G, Clark V, Suman A, George TJ Jr, Nelson DR. The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma. Aliment Pharmacol Ther. 2011 Jul;34(2):205-13. — View Citation

Cammà C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxì A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002 Jul;224(1):47-54. — View Citation

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced — View Citation

Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003 Feb;37(2):429-42. Review. — View Citation

Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Solà R, Rodés J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocell — View Citation

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, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, B — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Survival rate during the study period	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)
Secondary	Time to progression (TTP)	Time form the enrollment to the event of progression	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)
Secondary	Progression free survival (PFS)	Survival rate without progression of HCC	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)
Secondary	Median survival time (MST)	Median time of the patient survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)