Clinical trial NCT03518502: Sorafenib Monotherapy vs. TACE-sorafenib Sequential Therapy for HCC With Metastasis
Official title: Comparison of Efficacy Between Sorafenib Monotherapy vs. Transarterial Chemoembolization -Sorafenib Sequential Therapy in Hepatocellular Carcinoma Patients With Extrahepatic Metastasis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatocellular Carcinoma
Metastasis
Lead sponsor: Korea University
Sponsor class: OTHER
Collaborators: name: Korean Liver Cancer Study Group
First posted: 2018-05-08
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sorafenib monotherapy vs. transarterial chemoembolization-sorafenib sequential therapy
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 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 outcomes:
measure: Time to progression (TTP)
timeFrame: 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)
measure: Progression free survival (PFS)
timeFrame: 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)
measure: Median survival time (MST)
timeFrame: 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)
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Bucheon
country: Korea, Republic of
facility: Soonchunghyang University Bucheon Hospital
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hwasoon Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Marry Hospital, the Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
Study officials:
affiliation: Korea University Ansan Hospital
name: Hyung Joon Yim, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002 Jul;224(1):47-54. doi: 10.1148/radiol.2241011262.
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.
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, 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.
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 hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.
citation: 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. doi: 10.1111/j.1365-2036.2011.04697.x. Epub 2011 May 23.