UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Non-randomized controlled study comparing proton beam therapy and hepatectomy for resectable hepatocellular carcinoma(JCOG1315C, SPRING study)
Title of the study (Brief title)	Non-randomized controlled study comparing proton beam therapy and hepatectomy for resectable hepatocellular carcinoma(JCOG1315C, SPRING study)
Region	Japan

Condition
Condition	resectable hepatocellular carcinoma
Classification by specialty	Hepato-biliary-pancreatic medicine Hepato-biliary-pancreatic surgery Radiology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To confirm the non-inferiority of proton beam therapy compared with hepatectomy for resectable hepatocellular carcinoma
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase III

Assessment
Primary outcomes	overall survival
Key secondary outcomes	progression-free survival, patterns of failure, adverse events, acute non-hematological toxicities of Grade 3 or higher, late adverse reactions of Grade 3 or higher , serious adverse events, Child-Pugh score at 1, 3, and 5 years after the treatment, medical cost, quality of life (QOL), quality adjusted life years (QALY), incremental cost-effectiveness ratio (ICER)

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Device,equipment Maneuver
Interventions/Control_1	A: hepatectomy
Interventions/Control_2	B: proton beam therapy
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	79 years-old >=
Gender	Male and Female
Key inclusion criteria	1) single nodular hepatocellular carcinoma confirmed by dynamic contrast-enhanced CT or MRI of the liver within 28 days 2) cN0M0 diagnosed by dynamic contrast-enhanced CT or MRI of the upper abdomen and X ray or CT of the chest within 28 days 3) new-onset hepatocellular carcinoma 4) the maximum tumor diameter is larger than 3 cm and smaller than 12 cm 5) the margin of the tumor is at least 2 cm or more apart from the gastrointestinal tract 6) no invasion to or tumor thrombosis in the portal vein, the contralateral branches of the portal vein, or the first branch of the portal vein 7) no invasion to or tumor thrombosis in the inferior vena cava, the first branch of the hepatic vein, right inferior hepatic vein, or short hepatic vein 8) no invasion to or tumor thrombosis in the common bile duct or the first branch of the bile duct. 9) completely resectable by left lobectomy, anterior/posterior/lateral segmentectomy, extended subsegmentectomy, subsegmentectomy, or partial resection judged by the qualified surgeon and the cancer board including physicians of hepatobiliary and pancreatic surgery, hepatobiliary and pancreatic medicine, radiation oncology, and diagnostic radiology 10) No previous treatment for HCC 11) No ascites or hepatic encephalopathy 12) Age 20-79 years old 13) ECOG performance status of 0 or 1 14) Adequate organ functions i) White blood cell (WBC) >= 2,000/mm3 ii) Platelet >= 50,000/mm3 iii) Hemoglobin >= 8.0 g/dl iv) Total bilirubin < 2.0 mg/dl v) Serum albumin > 3.5 g/dl vi) Serum creatinine <= 1.5 mg/dl vii) Prothrombin activity > 70% 15) Written informed consent
Key exclusion criteria	1) synchronous or metachronous (within 5 years) malignancy except cancer with 5-year relative survival rate of 95% or more such as carcinoma in situ, intramucosal tumor, or early stage cancers. 2) active infection requiring systemic therapy 3) body temperature >= 38 degrees Celsius 4) female during pregnancy, within 28 days of postparturition, or during lactation 5) severe psychological disorder 6) receiving continuous systemic corticosteroid or immunosuppressant treatment 7) poorly controlled diabetes mellitus or receiving the routine administration of insulin 8) poorly controlled hypertension 9) unstable angina within 3 weeks, or with a history of myocardial infarction within 6 months 10) interstitial pneumonia, pulmonary fibrosis, or severe emphysema on chest CT 11) esophageal varices
Target sample size	290

Research contact person
Name of lead principal investigator	Tetsuo Akimoto
Organization	National Cancer Center Hospital East
Division name	Division of radiation Oncology and Particle Therapy
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan
TEL	04-7133-1111
Email	takimoto@east.ncc.go.jp

Public contact
Name of contact person	Tetsuo Akimoto
Organization	JCOG1315 Coordinating Office
Division name	Division of radiation Oncology and Particle Therapy, National Cancer Center Hospital East
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan
TEL	04-7133-1111
Homepage URL	http://www.jcog.jp/
Email	JCOG_sir@ml.jcog.jp

Sponsor
Institute	Japan Clinical Oncology Group (JCOG)
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Other
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	北海道大学病院（北海道） 筑波大学医学医療系（茨城県） 自治医科大学（栃木県） 栃木県立がんセンター（栃木県） 埼玉県立がんセンター（埼玉県） 国立がん研究センター東病院（千葉県） 千葉県がんセンター（千葉県） 杏林大学医学部（東京都） 帝京大学医学部（東京都） 国立がん研究センター中央病院（東京都） 横浜市立大学附属市民総合医療センター（神奈川県） 神奈川県立病院機構神奈川県立がんセンター（神奈川県） 金沢大学医学部（石川県） 静岡県立静岡がんセンター（静岡県） 名古屋市立西部医療センター（愛知県） 大阪府立病院機構大阪府立成人病センター（大阪府） 関西医科大学附属枚方病院（大阪府） 国立病院機構大阪医療センター（大阪府） 神戸大学医学部（兵庫県） 国立病院機構九州がんセンター（福岡県）

Other administrative information
Date of disclosure of the study information	2017 Year 06 Month 19 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2017 Year 05 Month 11 Day
Anticipated trial start date	2017 Year 06 Month 19 Day
Last follow-up date	2029 Year 12 Month 19 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	Advanced Medical Care B Proton beam therapy is provided at National Cancer Center Hospital East (Chiba), Hokkaido University Hospital (Hokkaido), Faculty of Medicine University of Tsukuba (Ibaraki), Shizuoka Cancer Center (Shizuoka), and Nagoya City West Medical Center (Aichi). Among these five institutions, hepatectomy is also provided at National Cancer Center Hospital East (Chiba) and Shizuoka Cancer Center (Shizuoka).

Management information
Registered date	2017 Year 06 Month 19 Day
Last modified on	2017 Year 06 Month 19 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031842