RCT of TAE Simultaneously Combined Thermal Ablation for Large Hepatocellular Carcinoma

Randomized Controlled Trial of Transarterial Embolization Simultaneously Combined Thermal Ablation for Large Hepatocellular Carcinoma

This study intends to evaluate the efficacy and safety of Transarterial embolization (TAE) simultaneously combined with thermal ablation for large hepatocellular carcinoma (HCC). Half participants will receive TAE simultaneously combined with thermal ablation and the other half receive TACE sequentially combined with thermal ablation, which is a conventional treatment for HCC patients.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma, Adult
• Intervention / Treatment: Drug: Embolic agents; Procedure: Simultaneously; Device: Ablation; Drug: Chemotherapy drug; Procedure: Sequentially

Detailed Description

The treatment method "Transarterial chemoembolization (TACE) sequentially combined with thermal ablation" is recommend for large HCC patients from NCCN Guideline and Chinese guideline "Diagnosis and Treatment of Primary Liver Cancer". The details of this sequential method consist one or more times of TACE followed by thermal ablation at least one month later to make the tumor completely inactivate. The thermal ablations include multiple applicators radiofrequency or microwave ablations. However, this method includes such disadvantages. 1) The limitation of lipiodol dosage in one TACE session is 30ml so that many patients needs more sessions of TACE; (2) Lipiodol and chemical drugs is easy to leak when patients have hepatic arteriovenous fistula. (3) Repeated TACE could cause more serious side effects. (4) Tumors of many patients are still not controlled or grow too large to ablate after TACEs which increases the metastasis risk and affects the efficacy and survival time.

However, TAE simultaneously combined with thermal ablation is another combination type which reduce the interval time between two procedures from one month to 1-3 days. TAE removes the chemical drugs and uses embolic agents such as Embosphere to obstruct vessels to enhance the effect of followed ablations. The main aim of reducing interval and remove chemical drugs is to make the tumor completely inactivate in one hospitalization like surgical operation, hoping bringing less side effects, better efficacy and longer survival time.

Thus the investigators will launch a prospective, multicenter randomized controlled clinical trial to compare the 3-years overall survival, safety, social and economic benefit of TAE simultaneously combined with ablation and TACE sequentially combined with ablation. The investigators expect to acquire Ia-level evidence-based medical evidence which can be accepted by the clinical guideline, popularizing, demonstrating our therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 410
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jinhua Huang, Ph.D; Phone Number: 0086-20-87343272; Email: huangjh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Jinhua Huang, Ph.D; Phone Number: 0086-20-87343447

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 to 70 years with estimated survival over 3 months
• Number of tumors < 3
• Diameter of tumor between 5cm to 15cm
• No portal vein trunk tumoral thrombus or inferior vena cava tumoral thrombus
• With arteriovenous fistula or arterioportal shunt fistula that can be completely embolized
• Child-Pugh class A or B/Child score > 7;ECOG score < 2
• Tolerable coagulation function or reversible coagulation disorders
• Laboratory examination test: WBC≥3.0×10E9/L; Hb≥3.0×10E9/L; PLT ≥50×10E9/L; INR < 2.3 or PT< 16.5s; Cr ≤ 145.5 umul/L
• Signed informed consent before recruiting

Exclusion Criteria:

• Diffused HCC
• With portal vein trunk tumoral thrombus
• With inferior vena cava tumoral thrombus or hepatic vein tumor thrombus
• With lymphatic metastasis or extra hepatic metastasis
• Child-Pugh class C and can't be improved by expectant treatment
• Untreatable coagulation disorders, severe hemogram abnormal and bleeding tendency
• Massive intractable ascites
• ECOG score > 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TAE combined ablation simultaneously; TAE simultaneously combined with ablation.The treatment interval is 1-3 days between two procedures. TAE using embolic agents(Lipiodol/Gelatin sponge/PVA particles(300～500μm)/Blank microspheres).	Drug: Embolic agents; Lipiodol/Gelatin sponge/PVA/Blank microspheres; Other Names: Embolization; Procedure: Simultaneously; 1-3 days; Other Names: Treatment interval; Device: Ablation; Radiofrequency ablation/Microwave ablation; Other Names: RFA/MWA
OTHER: TACE combined ablation sequentially; TACE sequentially combined thermal ablation.The treatment interval is 1 month between two procedures. TACE using chemotherapy drug(Doxorubicin/platinum agents) and embolic agents(Lipiodol/Gelatin sponge/PVA particles(300～500μm)/Blank microspheres).	Drug: Embolic agents; Lipiodol/Gelatin sponge/PVA/Blank microspheres; Other Names: Embolization; Device: Ablation; Radiofrequency ablation/Microwave ablation; Other Names: RFA/MWA; Drug: Chemotherapy drug; Doxorubicin/Platinum agents; Other Names: Chemotherapy; Procedure: Sequentially; 1 month; Other Names: Treatment interval

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From complete remission of the index large tumor to patient death or the completion of this trial	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence free survival	From complete remission of the index large tumor to tumor recurrence either in- or extra- hepatic or the completion of this trial	3 years
liver and renal function	Alanine aminotransferase,Ast,total bilirubin,albumin,creatinine,Urea nitrogen	3 years
Complications	number of participants with Complications	3 years
Times of interventional procedures	The number of procedures for each patient, either TACE/TAE or ablation	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Guangdong Provincial People's Hospital; Third Affiliated Hospital, Sun Yat-Sen University; Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 10, 2016
• First Posted (ESTIMATE): November 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: HCC; Embolization; Ablation; simultaneously; sequentially
• 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: TASAL

Plan for Individual participant data (IPD)

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