Arsenic Trioxide TACE and Intravenous Administration in Unresectable Hepatocellular Carcinoma

NCT ID: NCT01861912

Last Updated: 2013-06-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 258 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2016-12-31

Brief Summary

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.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arsenic trioxide TACE

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.

Group Type: ACTIVE_COMPARATOR

Arsenic trioxide TACE

Intervention Type: DEVICE

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

lipiodol

Intervention Type: DRUG

Lipiodol is used to dissolve arsenic trioxide for TACE,with the dosage decided according to the volume of the target lesion.

Arsenic trioxide TACE+IV

1. 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.

2. 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.

Group Type: EXPERIMENTAL

Arsenic trioxide TACE

Intervention Type: DEVICE

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

Intervention Type: DRUG

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.

lipiodol

Intervention Type: DRUG

Lipiodol is used to dissolve arsenic trioxide for TACE,with the dosage decided according to the volume of the target lesion.

NaCl solution

Intervention Type: DRUG

250ml NaCl solution is used to dissolve the arsenic trioxide for intravenous infusion.

Interventions

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

Intervention Type: DEVICE

Arsenic trioxide intravenous infusion

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.

Intervention Type: DRUG

lipiodol

Lipiodol is used to dissolve arsenic trioxide for TACE,with the dosage decided according to the volume of the target lesion.

Intervention Type: DRUG

NaCl solution

250ml NaCl solution is used to dissolve the arsenic trioxide for intravenous infusion.

Intervention Type: DRUG

Eligibility Criteria

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:

1. Neutrophil count≥1.5×109/L, platelet count≥60×109 /L; hemoglobin≥85g/L;

2. 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;

3. Amylase and lipase≤1.5 times the upper limit of the normal range

4. Serum creatinine≤20 g/L

5. Prothrombin time international normalized ratio ≤1.7; or prothrombin time≤4seconds above control;

6. 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:

1. CT / MRI showed diffuse lesions;

2. Extrahepatic metastasis (metastasis in lungs not included);

3. Invasion in the main portal vein / vena cava or other major vascular;

4. Previous shunt surgery;

5. PreviousTACE or transarterial embolization for HCC, unless there is a untreated lesion;

6. Hepatic encephalopathy in the past or present;

7. Current ascites requiring treatment;

• Medical history and concomitant diseases:

1. 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;

2. 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：

1. Hyponatremia, serum sodium <130 mmol / L；

2. 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:

1. Condensation treatment (e.g., warfarin or heparin);

2. Chronic antiplatelet therapy (Aspirin ≥ 300 mg / day; clopidogrel ≥ 75 mg / day);

3. Radiotherapy within 4 weeks;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ligong Lu

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ligong Lu, Doctor

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Other Identifiers

GDREC2013109H(R1)

Identifier Type: -

Identifier Source: org_study_id