Clinical trial NCT01861912: Arsenic Trioxide TACE and Intravenous Administration in Unresectable Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Carcinoma, Hepatocellular
Keywords: Carcinoma, Hepatocellular
Arsenic trioxide
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2013-05-24
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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;

Primary outcomes:
measure: Time to Progression
timeFrame: 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 outcomes:
measure: Overall Survival
timeFrame: 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.
measure: Quality of Life
timeFrame: 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.
measure: Safety
timeFrame: 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.
Other outcomes:
measure: Extrahepatic Metastasis Rate
timeFrame: 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.
measure: Recurrence Rate
timeFrame: 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.
Locations:
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Ligong Lu, Doctor
role: PRINCIPAL_INVESTIGATOR
References: