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

Study Overview
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Brief Summary
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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.

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

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: TACE containing As2O3
* Drug: TACE containing placebo


Participation Criteria
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Eligibility Criteria
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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>3*19^9/L;(2)hemoglobin≥8.5g/dl;(3)platelet count ≥50*10^9/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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to progression |  | From date of randomization until the date of first documented progression, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | patients proportion of CR and PR according to mRECIST | every 3 months from randomization until the date of first documented progression, up to 24 months | 
| progression free survival | survival from randomization to the date of first documented progression according to the mRECIST criterion | From date of randomization until the date of first documented progression, up to 24 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Hepatocellular, primary liver cancer, primary hepatocellular carcinoma, transarterial chemoembolization, Chemoembolization, Therapeutic, arsenic trioxide, arsenous anhydride, diarsenic trioxide, randomized controlled trial, multicenter study, HCC, TACE