UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Randomized Controlled Trial Comparing Efficacy of Sorafenib versus Sorafenib In combination with Low dose cisplatin /fluorouracil hepatic arterial InfUSion chemotherapy in Patients with Advanced Hepatocellular Carcinoma(SILIUS Phase III)
Title of the study (Brief title)	SILIUS Phase III
Region	Japan

Condition
Condition	HCC
Classification by specialty	Hepato-biliary-pancreatic medicine Radiology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the efficacy of sorafenib in combination with Low dose cisplatin/fluorouracil hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase III

Assessment
Primary outcomes	Overall Survival
Key secondary outcomes	Overall Survival Objective Response Rate Tumor markers Safety Biomarker predicting the efficacy

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Cluster
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine Maneuver
Interventions/Control_1	Sorafenib
Interventions/Control_2	Low-doseFP+Sorafenib
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) 20 Years and older. 2) Life expectancy of at least 12 weeks at the pre-treatment evaluation. 3) Advanced hepatocellular carcinoma with histological evidence on a biopsy specimen, or typical findings by dynamic CT or CT during hepatic arteriography/arterioportography. 4) Not suitable for resection or local ablation therapy or transcatheter arterial chemoembolization. 5) ECOG Performance status of 0 or 1. 6) Cirrhotic status of Child-Pugh class A. 7) Adequate bone marrow, liver and renal function, as assessed by the following laboratory requirements: a) Hemoglobin >= 8.5 g/dl b) Granulocyte >= 1500/mm3 c) Platelet count >= 50,000 /mm3 d) PT-INR <= 2.3 e) Total serum bilirubin <= 2 mg/dl f) AST and ALT <= 6 times upper limit of normal g) Serum creatinine <= 1.5 times upper limit of normal h) Amylase <= 2 times upper limit of normal 8) Written Informed Consent must be obtained.
Key exclusion criteria	1) Previous malignancy 2) Renal failure 3) Any heart disease as follows a) Congestive heart failure defined as NYHA class III or IV b) Active coronary artery disease or ischemic heart disease such as cardiac infarction within 6 months prior to screening c) Serious cardiac arrhythmia d) Serious hypertension 4) Active clinically serious infections except for HBV and HCV 5) Active chicken pox. 6) Auditory disorder. 7) Known history of HIV infection. 8) Known metastatic or meningeal tumors. 9) Extrahepatic tumor spread which affects patient's prognosis 10) History of seizure disorder. 11) Clinically significant gastrointestinal bleeding within 4 weeks prior to study entry. 12) Embolization or infarction such as transient ischemic disease, deep vein thrombosis, pulmonary embolization. 13) Any history of treatment as follows: a) Treatment with the agent which induces CYP3A4 b) Surgical procedure within 4 weeks prior to start of study drug c) History of organ allograft 14) Patients unable to swallow oral medications. 15) Gastrointestinal disease that may affect to the absorption of drug or pharmacokinetics. 16) Medication that may affect to the absorption of drug or pharmacokinetics. 17) Any disease or disorder that may affect the evaluation of study drug. 18) Entry to the other clinical trial within 4 weeks prior to entry to this study. 19) Pregnant or breast-feeding patients. 20) Known allergy to the investigational agent or any agent given in association with this trial. 21) Substance abuse, medical, psychological or social conditions that, in the judgment of the investigator, is likely to interfere with the patient's participation in the study or evaluation of the stuy results. 22) Any condition that is unstable or could jeopardize the safety of the patient and its compliance in the study, in the investigator's judgment.
Target sample size	190

Research contact person
Name of lead principal investigator	Masatoshi Kudo
Organization	Kinki University Faculty of Medicine
Division name	Department of Gastroenterology and Hepatology
Address	377-2, Oono-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
TEL	072-366-0221
Email

Public contact
Name of contact person	Kazuomi Ueshima
Organization	Kinki University Faculty of Medicine
Division name	Department of Gastroenterology and Hepatology
Address	377-2, Oono-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan
TEL	072-366-0221
Homepage URL
Email	kaz-ues@med.kindai.ac.jp

Sponsor
Institute	SILIUS Trial Group,Japan Ministry of Health, Labour and Welfare
Institute
Department

Funding Source
Organization	A grant-in-aid for Scientific Research from the Ministry of Health, Labour and Welfare
Organization
Division
Category of Funding Organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

近畿大学医学部付属病院（大阪府） 国立がんセンター中央病院（東京都） 大垣市民病院（岐阜県）　 杏林大学医学部付属病院（東京都） 国立がんセンター東病院（千葉県） 大阪大学医学部付属病院（大阪府） 京都大学医学部付属病院（京都府） 熊本大学医学部付属病院（熊本県） 広島大学医学部付属病院（広島県） 山口大学医学部付属病院（山口県） 久留米大学医療センター（福岡県） 千葉大学医学部附属病院（千葉県） 武蔵野赤十字病院（東京都） 大阪赤十字病院（大阪府） 財団法人佐々木研究所附属杏雲堂病院（東京都） 岡山大学医学部付属病院（岡山県） 市立池田病院（大阪府） 川崎医科大学（岡山県） 徳島大学医学部（徳島県） 順天堂大学医学部附属練馬病院（東京都） 宮崎医療センター病院（宮崎県） 札幌厚生病院（北海道） 札幌医科大学医学部（北海道）　 高松赤十字病院（香川県） 三重大学医学部附属病院（三重県） 岐阜市民病院（岐阜県） 広島市立広島市民病院（広島県） 長崎医療センター（長崎県） 済生会新潟第二病院（新潟県）

Other administrative information
Date of disclosure of the study information	2010 Year 10 Month 04 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2010 Year 09 Month 30 Day
Anticipated trial start date	2010 Year 10 Month 01 Day
Last follow-up date	2013 Year 09 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2010 Year 10 Month 02 Day
Last modified on	2017 Year 03 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005115