Back to resultsTranscatheter Arterial Chemoembolization (TACE) in Combination With Arsenic Trioxide Versus TACE in the Treatment of Middle-advanced Primary Hepatocellular Carcinoma (HCC) Patients
Primary Purpose
Primary Hepatocellular Carcinoma
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
TACE
Arsenic trioxide
Sponsored by
About this trial
This is an interventional treatment trial for Primary Hepatocellular Carcinoma
Eligibility Criteria
- Subject is 18-80 years old.
- Subject has no portal stem vein tumor thrombus.
- 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.
- 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.
- 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.
- Haematology: white blood cell count ≥3.0×10^9/L; hemoglobin≥10 g/dL; blood platelet count≥80×10^9/L
- 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.
- International normalized ratio (INR) is ≤ 2.3 or prothrombin time (PT) is ≤3 seconds than upper limit of normal control.
- Echocardiogram indicated a left ventricular ejection fraction (LVEF) of >50%.
- Subject has a liver function Child-Pugh class A or B.
- Subject is not pregnant or lactating.
- 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.
- 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.
- Subject had no history of systemic chemotherapy.
- Subject has no any other concomitant anticancer therapies, such as local radiotherapy, systemic chemotherapy and molecular targeted therapy.
- Subject and (or) guardian is able to understand this study and willing to provide written, informed consent to participate in this clinical study.
Sites / Locations
- Guizhou Cancer Hospital
- Guizhou Province Tumor Hospital
- Hunan Provincial People's Hospital
- Hunan Cancer Hospital
- Xiangya Hospital Central South University
- The First Affiliated Hospital of University of South China
- Jiangsu Province Hospital
- Xinjiang Medical University Cancer Hospital
- The Tumor Hospital of Yunnan Province
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
TACE plus Arsenic Trioxide
TACE
Arm Description
Patients in this group are to receive a single dose of TACE treatment on day 1, followed by arsenic trioxide at 10 mg/day for 14 days (day 8-21). TACE treatment is repeated every 9 weeks while arsenic trioxide every 3 weeks for treatment duration of 27 weeks. At least 3 cycles of arsenic trioxide are administrated.
Patients in this group are to receive a single dose of TACE treatment on day 1. TACE treatment is repeated every 9 weeks for 27 weeks.
Outcomes
Primary Outcome Measures
Progression free survival
Progression free survival (PFS) is defined as the time interval from the day of the random assignment to the first evidence of progression or death.
Secondary Outcome Measures
Objective response rate
Tumor response is defined as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST and will be assessed by the investigators. The tumor objective response rate (ORR) is calculated per treatment arm as the proportion of randomized patients having a confirmed best response of CR or PR.
Overall Survival
Overall survival will be measured from the date of randomization up to the date of death of any cause
Incidence of adverse events
Toxicities will be evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v 4.0.
Full Information
NCT ID
NCT02956772
First Posted
November 2, 2016
Last Updated
February 21, 2017
Sponsor
Hunan Provincial People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02956772
Brief Title
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
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Unknown status
Study Start Date
November 2016 (undefined)
Primary Completion Date
November 2019 (Anticipated)
Study Completion Date
November 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hunan Provincial People's Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
190 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TACE plus Arsenic Trioxide
Arm Type
Experimental
Arm Description
Patients in this group are to receive a single dose of TACE treatment on day 1, followed by arsenic trioxide at 10 mg/day for 14 days (day 8-21). TACE treatment is repeated every 9 weeks while arsenic trioxide every 3 weeks for treatment duration of 27 weeks. At least 3 cycles of arsenic trioxide are administrated.
Arm Title
TACE
Arm Type
Active Comparator
Arm Description
Patients in this group are to receive a single dose of TACE treatment on day 1. TACE treatment is repeated every 9 weeks for 27 weeks.
Intervention Type
Drug
Intervention Name(s)
TACE
Intervention Description
After the puncture of femoral artery via Seldinger method, a catheter was inserted and digital celiac axis or hepatic arteriography performed. Then a microcatheter was used to infuse chemotherapeutic agent (30 to 60 mg of pirarubicin) mixed with 5 to 20 mL of Lipiodol Ultra-Fluid. Embosphere microspheres (size of 100 to 300 um) were inserted for embolization.
Intervention Type
Drug
Intervention Name(s)
Arsenic trioxide
Intervention Description
Arsenic trioxide 10 mg is put into 500 ml saline solution and then administrated by continuous intravenous drip for 5 hours during a treatment day.
Primary Outcome Measure Information:
Title
Progression free survival
Description
Progression free survival (PFS) is defined as the time interval from the day of the random assignment to the first evidence of progression or death.
Time Frame
2-year
Secondary Outcome Measure Information:
Title
Objective response rate
Description
Tumor response is defined as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST and will be assessed by the investigators. The tumor objective response rate (ORR) is calculated per treatment arm as the proportion of randomized patients having a confirmed best response of CR or PR.
Time Frame
2-year
Title
Overall Survival
Description
Overall survival will be measured from the date of randomization up to the date of death of any cause
Time Frame
2-year
Title
Incidence of adverse events
Description
Toxicities will be evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v 4.0.
Time Frame
Up to 2 years through study completion
Other Pre-specified Outcome Measures:
Title
Quality of life using EuroQol five dimensions five levels questionnaire
Time Frame
Baseline and week 6, 12, 18, 24 and 30 using EuroQol five dimensions five levels questionnaire
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Subject is 18-80 years old.
Subject has no portal stem vein tumor thrombus.
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.
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.
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.
Haematology: white blood cell count ≥3.0×10^9/L; hemoglobin≥10 g/dL; blood platelet count≥80×10^9/L
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.
International normalized ratio (INR) is ≤ 2.3 or prothrombin time (PT) is ≤3 seconds than upper limit of normal control.
Echocardiogram indicated a left ventricular ejection fraction (LVEF) of >50%.
Subject has a liver function Child-Pugh class A or B.
Subject is not pregnant or lactating.
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.
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.
Subject had no history of systemic chemotherapy.
Subject has no any other concomitant anticancer therapies, such as local radiotherapy, systemic chemotherapy and molecular targeted therapy.
Subject and (or) guardian is able to understand this study and willing to provide written, informed consent to participate in this clinical study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lin Long, Dr.
Phone
86-13507476175
First Name & Middle Initial & Last Name or Official Title & Degree
Hua Xiang, Dr.
Phone
85-13667367061
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hua Xiang, Dr.
Organizational Affiliation
Hunan Provincial People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guizhou Cancer Hospital
City
Guiyang
State/Province
Guizhou
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shi Zhou, Dr.
Email
258600801@qq.com
Facility Name
Guizhou Province Tumor Hospital
City
Guiyang
State/Province
Guizhou
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junxiang Li, Dr.
Email
258600801@qq.com
Facility Name
Hunan Provincial People's Hospital
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410001
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hua Xiang, Dr.
Phone
+86-13667367061
First Name & Middle Initial & Last Name & Degree
Lin Long, Dr.
Phone
+86-13507476175
Email
doclongll@163.com
Facility Name
Hunan Cancer Hospital
City
Changsha
State/Province
Hunan
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guowen LI, Dr.
Email
liguowen@hnszlyy.com
Facility Name
Xiangya Hospital Central South University
City
Changsha
State/Province
Hunan
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunhui Zhou, Dr.
Email
zhouchunhui2016@163.com
Facility Name
The First Affiliated Hospital of University of South China
City
Hengyang
State/Province
Hunan
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Youhua Wu, Dr.
Email
330270372@qq.com
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhen-Qiang Yang, Dr.
Email
ntdoctoryang@hotmail.com
Facility Name
Xinjiang Medical University Cancer Hospital
City
Urumqi
State/Province
Xinjiang
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shufa Yang, Dr.
Email
yangshufa2013@sina.com
Facility Name
The Tumor Hospital of Yunnan Province
City
Kunming
State/Province
Yunnan
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming Huang, Dr.
Email
huangming4328@sina.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Transcatheter Arterial Chemoembolization (TACE) in Combination With Arsenic Trioxide Versus TACE in the Treatment of Middle-advanced Primary Hepatocellular Carcinoma (HCC) Patients
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