Clinical trial NCT02956772: Transcatheter Arterial Chemoembolization (TACE) in Combination With Arsenic Trioxide Versus TACE in the Treatment of Middle-advanced Primary Hepatocellular Carcinoma (HCC) Patients
Official title: A Prospective Multicenter Randomized Controlled Open-label Trial of Transcatheter Arterial Chemoembolization (TACE) in Combination With Arsenic Trioxide Versus TACE in the Treatment of Middle-advanced Primary Hepatocellular Carcinoma (HCC) Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Primary Hepatocellular Carcinoma
Lead sponsor: Hunan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2016-11-06
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A multicentre, randomized, open-label, parallel-group, active controlled study.

Detailed description: Primary hepatocellular carcinoma (HCC) is one of the most common types of cancer and accounts for significant morbidity and mortality worldwide. Notably, more than half of the new HCC cases and deaths develop in China. Transarterial chemoembolization (TACE) has been proposed as the first-line therapeutic strategy for the treatment of patients with unresectable HCC. However, TACE has several limitations itself which might be potentially associated with tumor metastasis and relapse.

Recent studies have demonstrated that arsenic trioxide (As2O3) can act as the first-line therapeutic option in the treatment of acute promyelocytic leukemia. Thereafter, several small studies in China showed promising clinical benefits when As2O3 is administrated among the HCC patients. With these preliminary results, the investigators are planning to carry out a multicenter randomized controlled trial through which to explore the potential efficacy and safety of adjuvant As2O3 treatment for HCC patients.

Eligibility criteria: 1. Subject is 18-80 years old.
2. Subject has no portal stem vein tumor thrombus.
3. Subject has primary middle-advanced liver cancer of Barcelona Clinic Liver Cancer stages B/C inappropriate for surgical resection or other locoregional therapy and still presents with tumor lesions in the liver.
4. Subject has evaluable tumor lesion(s) (using Magnetic Resonance Imaging /Computed Tomography) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1: single lesion size ≥5cm or at least one lesion of \>3cm in size when 2-3 lesions exist or there are 4 or more lesions.
5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤1, Fibrosis index based on 4 factors (FIB-4)≤6 and an expected survival time of 12 weeks or more.
6. Haematology: white blood cell count ≥3.0×10\^9/L; hemoglobin≥10 g/dL; blood platelet count≥80×10\^9/L
7. Blood biochemistry: serum albumin ≥2.8 g/dL, total bilirubin ≤2 mg/dL or ≤34.2 umol/L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 times of upper limit of normal (ULN); amylase and lipase ≤ 1.5 times of ULN; serum creatinine ≤2.0 mg/dL or \< 1.5 times of ULN; estimated creatinine clearance ≥60 mL/min.
8. International normalized ratio (INR) is ≤ 2.3 or prothrombin time (PT) is ≤3 seconds than upper limit of normal control.
9. Echocardiogram indicated a left ventricular ejection fraction (LVEF) of \>50%.
10. Subject has a liver function Child-Pugh class A or B.
11. Subject is not pregnant or lactating.
12. Female subjects must be infertile or agree to take effective contraceptives; male subjects and their partners of reproductive potential must also agree to use appropriate contraceptives.
13. Subject had no second tumor in the last 5 years, excluding skin basal cell carcinoma or skin squamous carcinoma or any other carcinoma in situ.
14. Subject had no history of systemic chemotherapy.
15. Subject has no any other concomitant anticancer therapies, such as local radiotherapy, systemic chemotherapy and molecular targeted therapy.
16. Subject and (or) guardian is able to understand this study and willing to provide written, informed consent to participate in this clinical study.

Primary outcomes:
measure: Progression free survival
timeFrame: 2-year
Secondary outcomes:
measure: Objective response rate
timeFrame: 2-year
measure: Overall Survival
timeFrame: 2-year
measure: Incidence of adverse events
timeFrame: Up to 2 years through study completion
Other outcomes:
measure: Quality of life using EuroQol five dimensions five levels questionnaire
timeFrame: Baseline and week 6, 12, 18, 24 and 30 using EuroQol five dimensions five levels questionnaire
Locations:
city: Guiyang
country: China
facility: Guizhou Cancer Hospital
state: Guizhou
city: Guiyang
country: China
facility: Guizhou Province Tumor Hospital
state: Guizhou
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital of University of South China
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Urumqi
country: China
facility: Xinjiang Medical University Cancer Hospital
state: Xinjiang
city: Kunming
country: China
facility: The Tumor Hospital of Yunnan Province
state: Yunnan
Study officials:
affiliation: Hunan Provincial People's Hospital
name: Hua Xiang, Dr.
role: PRINCIPAL_INVESTIGATOR
References: