Transcatheter Arterial Chemoembolization (TACE) in Combination With Arsenic Trioxide Versus TACE in the Treatment of Middle-advanced Primary Hepatocellular Carcinoma (HCC) Patients

February 21, 2017 updated by: Xiang Hua, Hunan Provincial People's Hospital

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

190

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lin Long, Dr.
  • Phone Number: 86-13507476175

Study Contact Backup

  • Name: Hua Xiang, Dr.
  • Phone Number: 85-13667367061

Study Locations

  • China
    • Guizhou
      • Guiyang, Guizhou, China
      • Guiyang, Guizhou, China
        • Guizhou Province Tumor Hospital
        • Contact:
    • Hunan
      • Changsha, Hunan, China
      • Changsha, Hunan, China
      • Changsha, Hunan, China, 410001
        • Hunan Provincial People's Hospital
        • Contact:
          • Hua Xiang, Dr.
          • Phone Number: +86-13667367061
        • Contact:
      • Hengyang, Hunan, China
        • The First Affiliated Hospital of University of South China
        • Contact:
    • Jiangsu
    • Xinjiang
      • Urumqi, Xinjiang, China
    • Yunnan
      • Kunming, Yunnan, China

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TACE plus Arsenic Trioxide
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.
Drug: TACE
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.
Drug: Arsenic trioxide
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.
Active Comparator: TACE
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.
Drug: TACE
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 2-year
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.
2-year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: 2-year
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.
2-year
Overall Survival
Time Frame: 2-year
Overall survival will be measured from the date of randomization up to the date of death of any cause
2-year
Incidence of adverse events
Time Frame: Up to 2 years through study completion
Toxicities will be evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v 4.0.
Up to 2 years through study completion

Other Outcome Measures

Outcome Measure
Time Frame
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
Baseline and week 6, 12, 18, 24 and 30 using EuroQol five dimensions five levels questionnaire

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hunan Provincial People's Hospital

Investigators

  • Principal Investigator: Hua Xiang, Dr., Hunan Provincial People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (Anticipated)

November 1, 2019

Study Completion (Anticipated)

November 1, 2020

Study Registration Dates

First Submitted

November 2, 2016

First Submitted That Met QC Criteria

November 4, 2016

First Posted (Estimate)

November 6, 2016

Study Record Updates

Last Update Posted (Actual)

February 23, 2017

Last Update Submitted That Met QC Criteria

February 21, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RACE16001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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