UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A randomized controlled trial of intra-arterial infusion of CDDP for hepatocellular carcinoma to prevent intra-hepatic metastasis after curative resection
Title of the study (Brief title)	Efficacy of intra-arterial infusion of CDDP after curative resection of hepatocellular carcinoma
Region	Japan

Condition
Condition	Patients after curative resection of hepatocellular carcinoma
Classification by specialty	Hepato-biliary-pancreatic medicine Hepato-biliary-pancreatic surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Hepatocellular carcinoma shows a high recurrent rate of 50 to 70% by 3 years after curative resection. A following treatment for the recurrence is restricted depending on the reduction of hepatic reserve. Therefore, it is critical to establish a preventive means for the recurrence in order to improve the survival and quality of life in patients with hepatocellular carcinoma. Hepatocellular carcinoma appears to recurrent as de novo or metastasis. It is reported that a successful treatment for a background liver disease significantly reduced de novo cancer development. On the other hand, to date no standard therapy has been established in terms of the prevention of the metastatic disease. In this trial, cases after curative resection of hepatocellular carcinoma are randomly divided into two groups: a) a group with no additional treatment and b) a group with an intra-arterial infusion of CDDP. At first, the safety issue of the infusion is evaluated. Then, the benefit of the infusion is evaluated on the basis of survival and recurrence-free survival. The effect of the infusion on a way of recurrence is also evaluated.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I,II

Assessment
Primary outcomes	1. Survival 2. Recurrence-free survival based on the evaluation using computed tomography, magnetic resonance imaging or ultrasound. The evaluation should be conducted every three months and has to be performed with computed tomography or magnetic resonance imaging at least once a 6-months. 3. A way of recurrence
Key secondary outcomes	1. RBC, WBC including differential count, Plt, PT-INR , Bleeding time 2. TP, Alb, AST, ALT, ALP, LDH, gamma-GTP, TBil, BUN, Crt, Na, K, Cl, ChE, T Chol, HbA1c 3. Alpha-fetoprotein, Fucosylated fraction of alpha-fetoprotein, Des-gamma-carboxy prothrombin 4. Urinalysis, Creatinine clearance 5. Background a. Age, Gender, Performance status, Chest X-ray, ECG b. HBsAg, anti-HCV, Child-Pugh classification, Indocyanine green retention rate R15 and clearance rate c. Characteristics of hepatocellular carcinoma: diagnostic modality, size, number, location, extension to hepatic and/or portal vein d. Alcoholic consumption, Blood transfusion, History of treatment for hepatocellular carcinoma and/or other diseases, History of allergy Items from #1 to #3 and #4 are evaluated once a month and just before each infusion of CDDP, respectively, while those in #5 are evaluated only at the enrolment.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	No treatment
Stratification	NO
Dynamic allocation	YES
Institution consideration	Institution is considered as a block.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Group A: No additional treatment after curative resection
Interventions/Control_2	Group B: Intra-arterial infusion of CDDP after curative resection An amount of 65mg/square meter of body surface of CDDP dissolved in saline at the concentration of 100 mg/70 ml is infused targeting the entire residual liver through a catheter inserted into an appropriate artery on 8, 20 and 32 weeks after curative surgical resection of hepatocellular carcinoma. The infusion rate is 3 mg/min, and two weeks earlier or later date is acceptable. When creatinine clearance is less than 90 ml/min or 70 ml/min, the amount of CDDP is reduced to 70% or 50%, respectively. If the previous infusion required additional treatments against adverse effects at Grade 3 of Common Terminology Criteria for Adverse Events v3.0 in terms of WBC, RBC and/or Plt, the amount of CDDP is reduced to 80% in the following infusion.
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	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Performance status is less than 2. 2. Child-Pugh classification is A or B. 3. The following criteria are satisfied. a. WBC is more than 3,000/microliter. b. Plt is more than 50,000/microliter. c. Hb is more than 8.0 g/dl. d. Total bilirubin is 3.0 g/dl or less. e. Creatinine clearance adjusted by a body square meter of 1.73 is more than 50 ml/min. 4. There are no other active malignant diseases. 5. No additional anti-cancer treatments have been executed for the last three months, which affect on over the liver. 6. A patient can give informed consent by himself/herself.
Key exclusion criteria	1. The history of severe allergic reaction against iodinated contrast medium and/or platinum-containing drugs. 2. A woman who is pregnant, lactating, or may become pregnant. 3. Hepatocellular carcinoma extended to the first branch of the portal vein or further. 4. Hepatocellular carcinoma extended to the inferior vena cava or further. 5. Dynamic CT or dynamic MRI revealed that hepatocellular carcinoma is solitary and 2 cm or less without vascular invasion. 6. Under interferon therapy. 7. A doctor responsible for the study judged to be inappropriate.
Target sample size	200

Research contact person
Name of lead principal investigator	Takeshi Suda
Organization	Niigata University Graduate School of Medical and Dental Sciences
Division name	Department of Gastroenterology and Hepatology
Address	1-757 Asahi-Machi, Chuo-Ku, Niigata, Niigata 951-8122
TEL	025-227-2207
Email	tspitt@med.niigata-u.ac.jp

Public contact
Name of contact person	Tomoyuki Kubota
Organization	Niigata Hepatocellular Carcinoma Therapy Study Group
Division name	Executive Office
Address	1-757 Asahi-Machi, Chuo-Ku, Niigata, Niigata 951-8122
TEL	025-227-2207
Homepage URL
Email	t-kubota@med.niigata-u.ac.jp

Sponsor
Institute	Niigata Hepatocellular Carcinoma Therapy Study Group
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
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

Other administrative information
Date of disclosure of the study information	2008 Year 05 Month 01 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2008 Year 03 Month 26 Day
Anticipated trial start date	2008 Year 05 Month 01 Day
Last follow-up date	2015 Year 04 Month 01 Day
Date of closure to data entry	2015 Year 04 Month 01 Day
Date trial data considered complete	2015 Year 04 Month 01 Day
Date analysis concluded	2016 Year 03 Month 01 Day

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

Management information
Registered date	2008 Year 04 Month 28 Day
Last modified on	2017 Year 04 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001369