UMIN-CTR Clinical Trial

Basic information
Public title	Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma
Acronym	Efficacy of HAIC with cisplatin before RFA for HCC
Scientific Title	Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma
Scientific Title:Acronym	Efficacy of HAIC with cisplatin before RFA for HCC
Region	Japan

Condition
Condition	hepatocellular carcinoma
Classification by specialty	Hepato-biliary-pancreatic medicine
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before RFA for the prevention of HCC recurrence
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase III

Assessment
Primary outcomes	Recurrence free survival
Key secondary outcomes	Incidence of adverse events Time to treatment failure with RFA Evaluation of treatment effect with tumor markers

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Placebo
Stratification	YES
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Maneuver
Interventions/Control_1	Hepatic arterial infusion chemotherapy with cisplatin and RFA
Interventions/Control_2	RFA
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	90 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Patients with hepatocellular carcinoma diagnosed by histologial examination or by imaging modalities 2) Less than or equal to 3 lesions, 30 mm or less in diameter 3) No extra-hepatic metastasis 4) No vascular invasion 5) Patients in Child-Pugh Class A or B 6) Male or female aged 20 years or older at the time of informed consent and younger than 90 years old 7) Patients with an ECOG Performance Status (PS) score of 0 or 1 8) No prior chemotherapy 9) Adequate organ function a) Neutrophil>=1500 /mm3 b) Hb>= 8.5 g/dL c) PLT>= 50000 /mm3 d) T-Bil<= 2.0 mg/dL e) AST<= within 5 times of normal limit ALT<= within 5 times of normal limit f) Cre<= within 1.5 times of normal limit 10) Written informed consent 11) Life expectancy of at least 6 months
Key exclusion criteria	1) Patients with histologically diagnosed mixed hepatocellular carcinoma or sarcomatoid carcinoma 2) History of any therapy to hepatocellular carcinoma 3) Patients unsuitable for RFA 4) Patients unsuitable for administration of CDDP 5) Patients who have simultaneous malignancies 6) Patients who have severe complications 7) Ascites or pleural effusion unresponsible to therapy 8) Patients inadequate in the investigator's judgement
Target sample size	90

Research contact person
Name of lead principal investigator	1st name Kazuhide Middle name Last name Yamamoto
Organization	Okayama university graduate school of medicine, dentistry, and pharmaceutical sciences
Division name	Department of gastroenterology and hepatology
Zip code	7008558
Address	2-5-1, Shikata-cho, Kita-ku, Okayama city, Okayama prefecture
TEL	090-235-7219
Email	kazuhide@md.okayama-u.ac.jp

Public contact
Name of contact person	1st name Kazuhiro Middle name Last name Nouso
Organization	Okayama university hospital
Division name	Department of gastroenterology
Zip code	7008558
Address	2-5-1, Shikata-cho, Kita-ku, Okayama city, Okayama prefecture
TEL	086-235-7219
Homepage URL
Email	nouso@cc.okayama-u.ac.jp

Sponsor
Institute	Okayama 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	Department of Gastroenterology, Okayama City Hospital, Okayama, Japan Medical Center for Clinical and Translational Research, Hiroshima University Hospital, Hiroshima, Japan Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan Department of Internal Medicine, Fukuyama City Hospital, Hiroshima, Japan Department of Internal Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Okayama university graduate school of medicine, dentistry, and pharmaceutical sciences, ethics committee
Address	2-5-1, Shikata-cho, Kita-ku, Okayama city, Okayama prefecture
Tel	086-235-6762
Email	MAE6605@adm.okayama-u.ac.jp

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	岡山大学病院（岡山県） 広島市民病院（広島県） 岡山市民病院（岡山県） 福山市民病院（広島県） 岡山赤十字病院（岡山県） 三豊総合病院（香川県）

Other administrative information
Date of disclosure of the study information	2012 Year 02 Month 11 Day

Related information
URL releasing protocol	https://pubmed.ncbi.nlm.nih.gov/33687130/
Publication of results	Published

Result
URL related to results and publications	https://pubmed.ncbi.nlm.nih.gov/33687130/
Number of participants that the trial has enrolled	74
Results	Recurrence-free survival rates at 1 (3) year in the HAIC group and non-HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320-1.091; p = 0.094]. Intrahepatic distant recurrence-free survival rate in the HAIC group was significantly better than that in the non-HAIC group (HR, 0.468; 95% CI, 0.235-0.896; p = 0.022).
Results date posted	2022 Year 08 Month 23 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2021 Year 03 Month 29 Day
Baseline Characteristics	Patients with naive early stage HCC diagnosed between August 2012 and July 2016 were recruited. All authors had access to the study data, and reviewed and approved the final manuscript.
Participant flow	After confirming the fulfillment of the eligibility criteria, the investigators registered the patients using a Web based system. The patients were then randomly assigned to receive either HAIC before RFA therapy (HAIC group) or RFA monotherapy (non HAIC group) in a 1 to 1 ratio. Allocation of the treatment group was performed with hos- pitals, tumor size, tumor number, and performance status as stratification factors. Patients were blinded to treatment allocation, although the investigators who conducted the HAIC therapy could not be blinded.
Adverse events	none
Outcome measures	Progression free survival Time to untreatable progression Adverse events Changes of tumor markers
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Main results already published
Date of protocol fixation	2012 Year 01 Month 24 Day
Date of IRB	2012 Year 01 Month 24 Day
Anticipated trial start date	2012 Year 03 Month 01 Day
Last follow-up date	2019 Year 07 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2012 Year 02 Month 11 Day
Last modified on	2022 Year 08 Month 23 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000008575