Arsenic Trioxide TACE and Intravenous Administration in Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether compared with arsenic trioxide TACE alone, arsenic trioxide TACE and intravenous administration could further prolong the overall survival.

Official Title
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Arsenic Trioxide TACE and Intravenous Administration Compared With Arsenic Trioxide TACE Alone in Unresectable Hepatocellular Carcinoma: a Randomized, Parallel, Controlled, Multi-center Clinical Study

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Device: Arsenic trioxide TACE
* Drug: Arsenic trioxide intravenous infusion
* Drug: lipiodol
* Drug: NaCl solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having signed informed consent; Histological or clinical diagnosis of hepatocellular carcinoma（HCC）; The target lesion should had at least one diameter line available for measurement, with the maximum diameter ≥5cm and ≤10cm； Barcelona Clinic Liver Cancer staging B or C; Child-Pugh liver function class: score≤7； Eastern Cooperative Oncology Group performance 0 or 1; At least 12 weeks life expectancy; Never received systemic treatment, such as oral molecularly targeted drugs and systemic chemotherapy; Be able to abide by the treatment and follow-up plan； Adequate results for laboratory tests, including: Neutrophil count≥1.5×109/L, platelet count≥60×109 /L; hemoglobin≥85g/L; Total bilirubin≤51.3 μmol/L, albumin≥28 g/L,and alanine aminotransferase and aspartate aminotransferase≤5 times the upper limit of the normal range; Amylase and lipase≤1.5 times the upper limit of the normal range Serum creatinine≤20 g/L Prothrombin time international normalized ratio ≤1.7; or prothrombin time≤4seconds above control; Left ventricular ejection fraction≥50% according to two-dimensional echocardiography; Contraception: during the trail and 12 weeks after the withdrawal, female of childbearing age (WOCBP), WOCBP whose male partners receive study drug or male must use appropriate contraceptive to avoid pregnancy; Exclusion Criteria: Disease should be excluded: CT / MRI showed diffuse lesions; Extrahepatic metastasis (metastasis in lungs not included); Invasion in the main portal vein / vena cava or other major vascular; Previous shunt surgery; PreviousTACE or transarterial embolization for HCC, unless there is a untreated lesion; Hepatic encephalopathy in the past or present; Current ascites requiring treatment; Medical history and concomitant diseases: Previous or current cancer other than HCC, unless it is cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis and T1). Cancer having received curative treatment 5 years ago will not be excluded; Disease history in the cardiovascular system as the following: (a)Uncontrolled hypertension；(b)Congestive heart failure in New York Heart Association grade 3 or 4; (c)Active coronary artery disease within 12 months, unstable angina or newly diagnosed angina/myocardial infarction;(d)Arrhythmia requiring drugs other than β-blockers and digoxin;(e)Valvular heart disease ≥ CTCAE grade 2； c) Corrected QT interval (Fridericia)> 450 ms confirmed by 2 ECGs in a row d) Thrombotic or embolic events within 6 months, e) Gastrointestinal bleeding within 6 months; f) Unstable and / or active stomach ulcer within 6 months, unless gastroscopy showed it to be fully recovered; g) Variceal bleeding within 6 months; h) Unhealed wound or ulcer, fracture within 3 months; i) Major surgery, open biopsy, or severe trauma within 3 weeks; j) History of organ transplant or subjects in the transplant waiting list; k) Uncontrolled abnormal thyroid function; l) HIV infection; m) Active or untreated hepatitis B; laboratory tests unsuitable for the enrollment： Hyponatremia, serum sodium <130 mmol / L； Hypokalemia, serum potassium <3.5 mmol / L； Allergic reactions to arsenic trioxide and any other drugs used in this trail; Forbidden therapies and/or drugs: Condensation treatment (e.g., warfarin or heparin); Chronic antiplatelet therapy (Aspirin ≥ 300 mg / day; clopidogrel ≥ 75 mg / day); Radiotherapy within 4 weeks;

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arsenic trioxide TACE<br>Arsenic trioxide TACE: arsenic trioxide powder 20mg dissolved in lipiodol(the dosage of lipiodol is decided according to the volume of the target lesion)is used for transcatheter arterial chemoembolization(TACE). TACE will be repeated after 4 6 weeks if it is necessary according to the assessment from imaging modalities. | Device: Arsenic trioxide TACE<br>* Arsenic trioxide powder 20mg dissolved in lipiodol(the dosage of lipiodol is decided according to the volume of the target lesion)is used for transcatheter arterial chemoembolization(TACE). TACE will be repeated after 4 6 weeks if it is necessary according to the assessment from imaging modalities<br>Drug: lipiodol<br>* Lipiodol is used to dissolve arsenic trioxide for TACE,with the dosage decided according to the volume of the target lesion.<br>|
| Experimental: Arsenic trioxide TACE+IV<br>Arsenic trioxide TACE: arsenic trioxide powder 20mg dissolved in lipiodol(the dosage of lipiodol is decided according to the volume of the target lesion)is used for transcatheter arterial chemoembolization(TACE). TACE will be repeated after 4 6 weeks if it is necessary according to the assessment from imaging modalities. Arsenic trioxide intravenous infusion: arsenic trioxide powder 0.15mg/Kg/d(maxim 10mg/d) dissolved in 250ml 0.9% sodium chloride solution is used for intravenous infusion.Every course will last for 3 weeks and the next course will be continued after 1 week suspension.Intravenous infusion will be suspended 3 days before and 7 14 days after TACE. | Device: Arsenic trioxide TACE<br>* Arsenic trioxide powder 20mg dissolved in lipiodol(the dosage of lipiodol is decided according to the volume of the target lesion)is used for transcatheter arterial chemoembolization(TACE). TACE will be repeated after 4 6 weeks if it is necessary according to the assessment from imaging modalities<br>Drug: Arsenic trioxide intravenous infusion<br>* Arsenic trioxide intravenous infusion: arsenic trioxide powder 0.15mg/Kg/d(maxim 10mg/d) dissolved in 250ml 0.9%NaCl solution is used for intravenous infusion.Every course will last for 3 weeks and the next course will be continued after 1 week suspension.Intravenous infusion will be suspended 3 days before and 7 14 days after TACE.<br>Drug: lipiodol<br>* Lipiodol is used to dissolve arsenic trioxide for TACE,with the dosage decided according to the volume of the target lesion.<br>Drug: NaCl solution<br>* 250ml NaCl solution is used to dissolve the arsenic trioxide for intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time to progression in our study is defined as the time from a patient's enrollment to the time for disease progression (according to Recist1.1). | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival in our study is defined as the time from a patient's enrollment to the time for death. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years. | 
| Quality of Life | Quality of life is assessed according to the FACT-Hep questionnaire. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years. | 
| Safety | Safety of our treatment plan will be assessed according to the Common Terminology Criteria for Adverse Events（CTCAE） 3.0 | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Hepatocellular, Arsenic trioxide