UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Safety Evaluation of the Maintenance treatment of Sorafenib in Hepatocellular carcinoma patients with Tumor thrombus after palliative surgery
Title of the study (Brief title)	Sorafenib for TT
Region	Japan

Condition
Condition	To evaluate the safety of sorafenib as a maintenance therapy after the surgical resection of hepatocellular carcinoma (HCC) with macroscopic vascular invasion (Vp, Vv, B).
Classification by specialty	Hepato-biliary-pancreatic medicine Surgery in general Hepato-biliary-pancreatic surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the safety of sorafenib as a maintenance therapy after the surgical resection of hepatocellular carcinoma (HCC) with macroscopic vascular invasion (Vp, Vv, B).
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I

Assessment
Primary outcomes	incidence of adverse events, hepatic reserve (ICGR-15), hepatic function (ALT, T-cho, T-Bil), and Child-Pugh class and score after the start of treatment with sorafenib
Key secondary outcomes	progression-free survival (PFS), time to progression (TTP), overall survival (OS)

Base
Study type	Interventional

Study design
Basic design	Cross-over
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	No treatment
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	When normal performance status and liver function are restored after the surgical resection of HCC with vascular invasion (#; 4 weeks to < 8 weeks after hepatectomy or ; 2 weeks to < 4 weeks after postoperative TAE), study treatment will be started as follows: 1)Subjects classified as Child-Pugh class A: Start sorafenib at an initial dose of 800 mg/day. 2)Subjects classified as Child Pugh B (7): Start sorafenib at an initial dose of 400 mg/day. When a subject meets the following dose-increase criteria 4 weeks later, increase the dose to 800 mg/day. When a subject fails to meet any of the criteria at this time, check his/her conformity to the criteria every 2 weeks.
Interventions/Control_2	After the first dose of sorafenib, treatment will be continued until recurrence is noted. When a subject has a disease-free interval of more than one year, treatment will be continued in principle for one year; subsequent treatment will be determined in accordance with the opinions of the subject's doctor and his/her wishes.
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	85 years-old >=
Gender	Male and Female
Key inclusion criteria	(1)Patients aged > 20 years to < 85 years; (2)Patients with recurrent disease who received prior treatment at least 2 years before surgery; (3)Patients in whom a preoperative diagnosis of HCC was made histologically or clinically (diagnostic imaging and tumor marker diagnosis); (4)Patients with preoperative evidence of macroscopic vascular invasion (Vp, Vv, B); (5)Patients with preoperative evidence of measurable disease on a contrast-enhanced CT or MRI scan; (6)Patients who underwent successful surgical resection of HCC with macroscopic vascular invasion, or those with gross residual disease after surgery who underwent postoperative TAE; (7)Patients without any carry-over effects of prior treatment or adverse reactions (prior to the study, a treatment-free period of > 4 weeks to < 8 weeks is required after surgery; for those with gross residual disease after surgery, a treatment-free period of > 2 weeks to < 4 weeks is required after postoperative TAE); (8)Patients with a Child-Pugh score of >7 (9)Patients with an ECOG performance status (PS) of 0 or 1; (10)Patients with intact function of vital organs (to be confirmed within 2 weeks before the start of study treatment); (a)Neutrophil count:>1,500/uL (b)Serum albumin: >3.0 g/dL (c)Platelets:>50,000/uL (d)Hemoglobin:>7.5 g/dL (e)Total bilirubin: <1.5 mg/dL (f)Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT):<200 IU/L (g)Serum creatinine: <1.5 x ULN at the study site (11)Patients who can comply with the study procedures including hospital visits, study treatment, and laboratory tests; and (12)Patients who gave written informed consent prior to the study.
Key exclusion criteria	(1)Patients treated with sorafenib or other molecular target drugs within 3 months before surgery; (2)Patients with a history of allergic reaction to sorafenib; (3)Pregnant and breastfeeding women or those who may possibly be pregnant; (4)Patients with serious complications (whether preoperative or postoperative); (5)Patients with distant metastasis; (6)Patients with other active malignancies (e.g., brain tumor); (7)Patients with underlying diseases other than viral hepatitis (e.g., autoimmune hepatitis, alcoholic hepatitis); (8)Patients with moderate or severe renal dysfunction (eGFR < 30 mL/min) including those on dialysis; (9)Patients with asthma; (10)Patients with uncontrolled hypertension or with thromboembolism, ischemic heart disease, unstable angina pectoris, heart failure, or cerebrovascular disorder that may affect the operability of the disease; (11)Patients with clinically relevant ascites (refractory ascites requiring therapeutic paracentesis); (12)Patients with previous liver transplantation; (13) Patients with esophageal varices that may cause bleeding (those who had gastrointestinal bleeding in the past month); (14)Patients with a current or past history of hepatic encephalopathy; (15)Patients under treatment with drugs affecting the activity of CYP3A4 or UGT1A9 (e.g., rifampicin) or drugs that may affect the serum concentration of sorafenib; (16)Patients orally taking crude drugs approved for the treatment of cancer (e.g., Sho-saiko-to); (17)Patients with diseases related to human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS); or (18)Patients considered to be ineligible for participation in the study by the investigator or subinvestigator.
Target sample size	12

Research contact person
Name of lead principal investigator	Norihiro Kokudo
Organization	Tokyo University Hospital
Division name	Hepato-Biliary-Pancreatic Surgery Division
Address	7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan
TEL
Email

Public contact
Name of contact person	Yosuke Inoue
Organization	Tokyo University Hospital
Division name	Hepato-Biliary-Pancreatic Surgery Division
Address	7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan
TEL	03-3815-5411
Homepage URL
Email

Sponsor
Institute	Tokyo University Hospital
Institute
Department

Funding Source
Organization	none
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

Other administrative information
Date of disclosure of the study information	2011 Year 07 Month 06 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2011 Year 05 Month 22 Day
Anticipated trial start date	2011 Year 06 Month 01 Day
Last follow-up date
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	2011 Year 07 Month 02 Day
Last modified on	2019 Year 01 Month 06 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000006989