Arsenic Trioxide TACE and Intravenous Administration in Unresectable Hepatocellular Carcinoma

Carcinoma, Hepatocellular Clinical Trial

— ACTION  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01861912
• Other study ID #: GDREC2013109H(R1)
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• First received: May 16, 2013
• Last updated: June 4, 2013
• Start date: June 2013
• Est. completion date: December 2016

Study information

• Verified date: June 2013
• Source: Guangdong General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 258
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 ß-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;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Device:
• 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

Drug:
• 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.
• lipiodol
Lipiodol is used to dissolve arsenic trioxide for TACE,with the dosage decided according to the volume of the target lesion.
• NaCl solution
250ml NaCl solution is used to dissolve the arsenic trioxide for intravenous infusion.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong General Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Extrahepatic Metastasis Rate	Extrahepatic metastasis rate is defined as the proportion of the extrahepatic metastasis for patients who were absent of extrahepatic metastasis at enrollment.	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.	No
Other	Recurrence Rate	Recurrence rate is defined as the proportion of the recurrence in the patients.	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.	No
Primary	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.	No
Secondary	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.	No
Secondary	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.	Yes
Secondary	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.	Yes