TACE Combined With Synchronous Radiofrequency /Microwave Ablation to Treat Large and Huge Hepatocellular Carcinoma

Study Overview
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Brief Summary
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It is a prospective and multi-center clinical research in China to compare the efficacy, safety and related impact factors between TACE alone and TACE combined with synchronous multi-point MWA/RFA for large and huge liver cancer.

Detailed Description
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It is an open random prospective phase III clinical trial conducted by Principal Investigator Professor Jian-Hua Wang. Investigators in twenty-five hospitals in China participate in. Patients with unresectable large HCC (>5cm in diameter) and huge HCC (>=10cm in diameter) are enrolled. The investigators propose to recruitment 280 patients who are randomly assigned into the combined group (treated with TACE and synchronous ablation) and the control group (treated with TACE alone) according to the proportion of 1:1, which means 140 patients in each group. The criteria of inclusion and exclusion, and the methods of lab tests, imaging modality and treatment procedures are the same.

Official Title
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Clinical Study of Transarterial Chemoembolization (TACE) Combined With Synchronous Radiofrequency /Microwave Ablation to Treat Large and Huge Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Procedure: Thermal Ablation
* Drug: EADM
* Drug: Ultra-fluid lipiodol
* Other: Gelatin sponge articles


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with primary liver cancer aged from 18-80 years, and life expectancy longer than three months; Patients with large HCC (>5cm in diameter) and huge HCC (≥10cm in diameter), including HCC and mixed type of liver cancer (HCC-ICC); Patients with no thrombus in main portal vein (PV) Patients' liver function classified as Child-Pugh A or B, ECOG PS ≤ 2; Patients without bleeding tendency or coagulation disorder, or with reversible coagulopathy after therapy; White blood cell count ≥ 3.0×10^9/L; Hemoglobin ≥ 8.5g/dl; Platelet ≥ 50×10^9/L; INR ≤ 2.3 or PT not exceeding the upper limit of reference 3 seconds; Blood creatinine less than 1.5 times of upper limit of reference; Patients and/or their relatives willing to join in the clinical trial and signing the informed consent. Exclusion Criteria: Patients with diffuse type of liver cancer; Cholangiocellular carcinoma Patients with main PV thrombus; Patients with hepatic vein thrombus; Patients with lymph node or distant metastasis outside of liver; Patients' liver function classified as Child-Pugh C and no improvement after treatment of liver protection; Patients with irreversible coagulation disorder and abnormality in blood routine test, or having obvious bleeding tendency; Patients with intractable massive ascites; Patients' ECOG PS >2; Patients complicated with active infection, especially cholangitis; Patients with severe disorders of heart, lungs, kidneys, or brain; Patients and/or their relatives refuse to anticipate this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thermal Ablation & TACE<br>Transarterial chemoembolization (TACE) is performed immediately following thermal ablation. EADM, ultra-fluid lipiodol and gelatin sponge articles are used in TACE. | Procedure: Thermal Ablation<br>* Thermal ablation in this trial includes radiofrequency ablation and microwave ablation, one of them can be chosen to be performed.<br>* Other names: Microwave ablation;Drug: EADM<br>* EADM is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: EADM 30-60 mg per patient,depending on the situation of the patient.<br>* Other names: Epirubicin;Drug: Ultra-fluid lipiodol<br>* Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .<br>* Other names: lipiodol;Other: Gelatin sponge articles<br>* Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.<br>|
| Active Comparator: TACE alone<br>Only TACE is performed. EADM, ultra-fluid lipiodol and gelatin sponge articles are used in TACE. | Drug: EADM<br>* EADM is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: EADM 30-60 mg per patient,depending on the situation of the patient.<br>* Other names: Epirubicin;Drug: Ultra-fluid lipiodol<br>* Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .<br>* Other names: lipiodol;Other: Gelatin sponge articles<br>* Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From the date of randomization until the date of death from any cause, assessed up to 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-Disease Progression | TTDP follow-up is done at three months interval after lesions defined as stable with treatment of TACE or ablation combined with synchronous TACE six months after enrollment until lesions are defined as disease progression. | From the date of first procedure of TACE or TACE combined with synchronous ablation until the time when the disease progresses from an intermediate to an advanced stage as defined by specific events, assessed up to 26 months | 
| Objective response rate (ORR) | The ratio of CR plus PR. The efficacy is defined as complete regression (CR), partial regression (PR), stable disease (SD) and progressive disease (PD) according to modified Response Evaluation Criteria in Solid Tumors (mRESIST) | Six months after the date of first procedure of TACE or TACE combined with synchronous ablation. | 
| Progression free survival(PFS) |  | From the date of first procedure of TACE or TACE combined with synchronous ablationto until the time when lesions are defined as disease progression or death by any cause,assessed up to 26 months. | 
| Numbers of TACE and TACE combined with ablation cycles | The times of the subjects undergoing TACE or TACE combined with ablation | From the date of randomization until the date of death, assessed up to 26 months. | 
| Number of participants with adverse events and severe adverse events in TACE alone and TACE combined with ablation groups | Serious or mild adverse events after treatment | From the date of randomization until the date of follow-up visit (30 days after the procedure of TACE or TACE combined with thermal ablation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, TACE, Thermal Ablation, Safety/Efficacy