UMIN-CTR Clinical Trial

Public title

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)

Acronym

SILIUS Phase III

Scientific Title

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)

Scientific Title:Acronym

SILIUS Phase III

Region

Japan

Condition

HCC

Classification by specialty

Hepato-biliary-pancreatic medicine

Radiology

Classification by malignancy

Malignancy

Genomic information

YES

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

Primary outcomes

Overall Survival

Key secondary outcomes

Overall Survival
Objective Response Rate
Tumor markers
Safety
Biomarker predicting the efficacy

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Masatoshi Kudo

Organization

Kinki University Faculty of Medicine

Division name

Department of Gastroenterology and Hepatology

Zip code

Address

377-2, Oono-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

TEL

072-366-0221

Email

Name of contact person

1st name
Middle name
Last name	Kazuomi Ueshima

Organization

Kinki University Faculty of Medicine

Division name

Department of Gastroenterology and Hepatology

Zip code

Address

377-2, Oono-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

TEL

072-366-0221

Homepage URL

Email

kaz-ues@med.kindai.ac.jp

Institute

SILIUS Trial Group,Japan Ministry of Health, Labour and Welfare

Institute

Department

Personal name

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

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2010

Year

10

Month

04

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2010

Year

09

Month

30

Day

Date of IRB

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

Other related information

Registered date

2010

Year

10

Month

02

Day

Last modified on

2017

Year

03

Month

22

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005115