Transarterial Ethanol Ablation(TEA) for Unresectable Hepatocellular Carcinoma(HCC)

A Comprehensive Analysis of Clinical Outcome, Treatment Toxicity and Tumor Response of Transarterial Ablation(TEA) for Unresectable Hepatocellular Carcinoma(HCC)

The objective of this trial was to evaluate the clinical outcome, treatment toxicity and tumor response of TEA for unresectable HCC.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: TEA

Detailed Description

Transarterial therapy has been playing an important role in the treatment algorithm for patients with multifocal or large intrahepatic lesions not eligible for surgical resection, transplantation, or local ablative therapy. Among the various options of transarterial therapy including chemoembolization (TACE), bland embolization, radioembolization, and TEA, chemoembolization is the only one that has been proven to be of survival benefits versus best supportive care in randomized controlled trials. TEA is a hybrid of bland embolization and chemical ablation. Utilizing a liquid agent of Lipiodol-ethanol mixture consisting of 33% ethanol by volume, TEA offers complete and long lasting embolization of both the arterioles and portal venules supplying the tumor and could possibly be more effective than particulate embolic agents in tumor vessel embolization. The component of ethanol very likely offers synergistic effect to embolization and causes tumor ablation.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong
  • Hong Kong, Hong Kong
    • Department of Clinicl Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong
  • Hong Kong, Hong Kong
    • Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinsese University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent by patient
• Age above 18 years
• Child-Pugh A or B cirrhosis
• Eastern Cooperative Oncology Group(ECOG) performance score 2 or below
• No serious concurrent medical illness
• No prior treatment or surgery for HCC
• Histologically or cytologically proven HCC except for lesions of size 1 to 2 cm, with typical features of HCC on two dynamic imaging techniques, or lesions larger than 2cm, with typical features on one dynamic imaging techniques, or lesions larger than 2cm with alpha feto protein(AFP) level > 200 ng/mL
• Unresectable disease without extra-hepatic involvement on chest X-ray(CXR) and CT
• Massive expansive tumor type with measurable lesion on CT
• Total tumor mass < 50% liver volume
• Tumor size ≤ 15cm in largest dimension
• Tumor number ≤ 5

Exclusion Criteria:

• History of prior malignancy except on the condition that the patient has been disease free for ≥ 3 years
• Concurrent ischemic heart disease or heart failure
• History of acute tumor rupture presenting with hemo-peritoneum
• Serum creatinine level > 180 umol/L
• Biliary obstruction not amenable to percutaneous drainage
• Child-Pugh C cirrhosis
• History of hepatic encephalopathy
• Intractable ascites not controllable by medical therapy
• History of variceal bleeding within last 3 months; serum total bilirubin level ≥ 50 umol/L
• Serum albumin level < 25g/L
• International normalized ratio(INR) > 1.5
• Extrahepatic metastasis
• Infiltrative or diffuse tumor
• Tumor number > 5
• Thrombosis of target hepatic artery
• Partial or complete thrombosis of the main portal vein; tumor invasion of portal branch of contralateral lobe
• Hepatic vein tumor thrombus
• Significant arterio-portal venous shunt
• Significant arterial-hepatic venous shunt

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Transarterial Ethanol Ablation (TEA); Two treatment sessions at 2 months apart were given and started within 4 weeks after randomization.

Procedure: TEA; Arterial feeders to tumors were identified and catheterized with a microcatheter to a branch supplying a Couinaud segment or subsegmental level for delivery of the therapeutic agent, which was Lipiodol-ethanol mixture at 2:1 ratio by volume for TEA (Lipiodol Ultrafluide, Guerbet, France; Dehydrated alcohol [absolute alcohol], Martindale Pharmaceuticals, United Kingdom). The agents were delivered under fluoroscopic control to completely fill up the vasculature of all tumors. The maximum total volume of Lipiodol-ethanol mixture or cisplatin emulsion to be delivered in one treatment session was 60 mL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival and treatment-related toxicity	Overall survival was defined as date of treatment to date of death from any cause. Patients alive at the end of follow-up were censored. Clinical and laboratory data were documented prospectively at baseline, during hospitalization, and at 7, 14, and 30 day, and 3, 6, 9, and 12 months. Laboratory findings were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.	Overall survival is studied from treatment to death from any cause, for an estimated period of up to 60 months. Treatment-related toxicity is studied up to 3 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression(TTP)	TTP was defined as date of treatment to date of first CT evidence of disease progression. Patient death during follow-up without CT progression was censored.	Time to progression is studied from treatment to disease progression, for an estimated period of up to 60 months.
Progression free survival(PFS)	PFS was defined as date of treatment to date of either first CT evidence of disease progression or death from any cause. Patients alive and free of progression at the end of follow-up were censored.	Progression free survival is studied from treatment to disease progression or death from any cause, for an estimated period of up to 60 months.
Tumor response	Treatment response of individual treated tumor lesions was evaluated with CT and classified according to a system combining the recommendation of European Association for the Study of the Liver and the guidelines of World Health Organization, which was considered a preferred method of response assessment following transarterial or locoregional therapies for HCC. Tumor response was classified into 4 categories: 1) complete response (CR), 2) partial response (PR), 3) static disease (SD), or 4) intralesional progression.	Tumor response is studied at 6 months after treatment

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: Prince of Wales Hospital, Shatin, Hong Kong
• Investigators: Principal Investigator: Simon CH Yu, MD, FRCR, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: April 15, 2013
• First Submitted That Met QC Criteria: April 18, 2013
• First Posted (Estimate): April 23, 2013

Study Record Updates

• Last Update Posted (Actual): September 3, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: VIR-13-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO