SEATH: Safety and Efficacy of Arsenic Trioxide Contained in TACE in the Treatment of HCC

Sponsor

First Hospital of China Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02018757

Collaborator

Sun Yat-sen University (Other), Zhongda Hospital (Other), Fudan University (Other), Xijing Hospital (Other)

250

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of the study is to determine whether transarterial chemoembolization containing arsenic trioxide is safe and effective in the treatment of intermediate-stage hepatocellular carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Drug: TACE containing As2O3 Drug: TACE containing placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Clinical Application Study of Transarterial Chemoembolization Containing Arsenic Trioxide in the Treatment of Hepatocellular Carcinoma

Study Start Date :

Jan 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: As2O3 Subjects will be treated with TACE containing As2O3	Drug: TACE containing As2O3 transarterial chemoembolization containing a mixture of 20mg of arsenic trioxide, 40mg of adriamycin and some dose of 40% ultra-fluid lipiodol Other Names: transarterial chemoembolization,TACE,As2O3,arsenious acid
Placebo Comparator: placebo Subjects will be treated with TACE containing placebo which mimics the arsenic trioxide	Drug: TACE containing placebo transarterial chemoembolization containing a mixture of 20mg of placebo, 40mg of adriamycin and some dose of 40% ultra-fluid lipiodol

Arm

Intervention/Treatment

Experimental: As2O3

Subjects will be treated with TACE containing As2O3

Drug: TACE containing As2O3

transarterial chemoembolization containing a mixture of 20mg of arsenic trioxide, 40mg of adriamycin and some dose of 40% ultra-fluid lipiodol

Other Names:

transarterial chemoembolization,TACE,As2O3,arsenious acid

Placebo Comparator: placebo

Subjects will be treated with TACE containing placebo which mimics the arsenic trioxide

Drug: TACE containing placebo

transarterial chemoembolization containing a mixture of 20mg of placebo, 40mg of adriamycin and some dose of 40% ultra-fluid lipiodol

Outcome Measures

Primary Outcome Measures

time to progression [From date of randomization until the date of first documented progression, up to 24 months]

Secondary Outcome Measures

objective response rate [every 3 months from randomization until the date of first documented progression, up to 24 months]
patients proportion of CR and PR according to mRECIST
progression free survival [From date of randomization until the date of first documented progression, up to 24 months]
survival from randomization to the date of first documented progression according to the mRECIST criterion
overall survival [From date of randomization until the date of death from any cause, up to 60 months]
Proportion of Participants with Adverse Events [every 3 months from randomization until the date of first documented progression, up to 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

accordance with primary hepatocellular carcinoma diagnosis standard：cytohistology standard or non-invasive standard.1）+2）a or 1）+2）b+3）of the following are the non-invasive diagnosis criteria:(1)patients with HBV or HCV related liver cirrhosis.(2)radiological lesion(s) in liver with arterial hypervascularity and venous or delayed phase washout: a.one kind of imaging technology diagnosis for those with lesions>2cm;b.two kinds of imaging technology obtains the consistent conclusion for lesions with diameter of 1-2 cm.(3)serum AFP level ≥400 ug/L lasting for more than 1 month or ≥200 ug/L lasting for more than 2 months, other diseases that may cause the AFP level increase can be excluded,such as pregnancy, genital or embryonic tumors and active hepatitis.
age of 18 to 75 year,male or female
life expectancy of 12 weeks
Barcelona Clinic Liver Cancer (BCLC)stage B
laboratory tests:(1)leukocyte>319^9/L;(2)hemoglobin≥8.5g/dl;(3)platelet count ≥5010^9/L,(4)ALT and AST were less than three times the normal limit;(5)albumin ≥ 3.0 g/dl;(6)total bilirubin acuities 3 mg/dl;(7)prothrombin time international standardization ratio (PT - INR) < = 2.3 or prothrombin time (PT)more than normal compared 3 seconds;(8)serum creatinine is less than 1.5 times the normal of the upper limit
patients with signed informed consent

Exclusion Criteria:

concomitant malignancies distinct from HCC currently or previously
allergic to subject agent(such as arsenic) or other agent related to the trial
BCLC stage 0,A,C or D
HCC accounting for the 70% of the liver size or more
liver function Child-Pugh score of C
ECOG score of 1 or higher
severe heart diseases,such as congestive heart failure with cardiac function of New York Heart Association(NYHA)functional class II or severe, active coronary disease(except for who with myocardial infarction for more than 6 months) and cardiac arrhythmia needing medical management(except for that controllable by β-blockers、calcium channel blockers and digoxin )
uncontrollable hypertension(diastolic blood pressure cannot be controlled below 90 mmHg even after antihypertension treatment by antihypertensive drugs).
active severe infection(grade 2 or higher according to NCI-CTCAE version 4.0)
active tuberculosis or pulmonary tuberculosis cannot be excluded
CNS malignancies, including intracranial metastases
gastrointestinal bleeding with clinical findings in the previous 30 days
chronic renal failure
pregnancy or breastfeeding
any other unstable conditions or circumstances possibly to jeopardise the safety or compliance of the subjects.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China
2	Zhongda Hospital Southeast University	Nanjing	Jiangsu	China
3	The First Hospital of China Medical University	Shenyang	Liaoning	China	110001
4	Xijing Hospital，Fourth Military Medical University	Xi'an	Shaanxi	China
5	Zhongshan Hospital Fudan University	Shanghai		China