TACE+RFA Versus TACE Alone for Intermediate-stage Hepatocellular Carcinoma

NCT ID: NCT02435953

Last Updated: 2025-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 242 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2025-10-31

Brief Summary

The current standard treatment for intermediate-stage HCC (BCLC stage B) is transcatheter arterial chemoembolization (TACE) alone. The combination of TACE with RFA has also reported to be an effective treatment for HCC. Some prospective studies have shown that TACE combined with RFA have better efficacy than any of them alone for early stage HCC (single tumor ≤5 cm). However, to the investigators' knowledge, there have not been any prospective studies to assess whether TACE combined sequentially with RFA is more effective than TACE alone for the treatment of intermediate-stage HCC. The investigators hypothesized that the combination of TACE and RFA might result in better patient survival than TACE alone. Thus, the purpose of this study was to prospectively compare the effects of sequential TACE-RFA with TACE alone for the treatment of intermediate-stage HCC. Intermediate-stage HCC in this study was defined as 2-3 intrahepatic lessions, largest tumor size 3-7 cm or 4-10 intrahepatic lessions, largest tumor size ≤7 cm; ECOG-PS 0; Child-pugh A or B7; no tumor thrombus or extrahepatic metastases.

Conditions

Hepatocellular Carcinoma; Chemoembolization, Therapeutic; Ablation Techniques, RFA

Keywords

Hepatocellular Carcinoma,TACE,Chemoembolization, RFA,Intermediate-stage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TACE-RFA

RFA follows TACE when achieving ablation eligibility criteria defined in this study, with no more than four sessions of TACE.

Group Type: EXPERIMENTAL

TACE

Intervention Type: PROCEDURE

A catheter (or a microcatheter for cases where small vessels and branches cannot be accessed with a standard angiographic catheter) will be advanced selectively or superselectively into the right or left hepatic artery or the feeding arteries directly supplying the tumor. Depending on tumor size, location, blood supply, and liver function, the interventional radiologist administers a cytotoxic agent and lipiodol emulsion (30 mg lobaplatin, 30 mg pirarubicin, and \< 15 mL lipiodol) through the catheter. Following drug infusion, embolization of the tumor vessels will be routinely performed using gelatin sponge particles.

RFA

Intervention Type: PROCEDURE

Commercial electrode systems are used and the ablation therapy is to be performed according to manufacturer's standard recommendations. All lesions are targeted with CT images during the RFA procedure.

TACE alone

On-demand TACE.

Group Type: ACTIVE_COMPARATOR

TACE

Intervention Type: PROCEDURE

A catheter (or a microcatheter for cases where small vessels and branches cannot be accessed with a standard angiographic catheter) will be advanced selectively or superselectively into the right or left hepatic artery or the feeding arteries directly supplying the tumor. Depending on tumor size, location, blood supply, and liver function, the interventional radiologist administers a cytotoxic agent and lipiodol emulsion (30 mg lobaplatin, 30 mg pirarubicin, and \< 15 mL lipiodol) through the catheter. Following drug infusion, embolization of the tumor vessels will be routinely performed using gelatin sponge particles.

Interventions

TACE

A catheter (or a microcatheter for cases where small vessels and branches cannot be accessed with a standard angiographic catheter) will be advanced selectively or superselectively into the right or left hepatic artery or the feeding arteries directly supplying the tumor. Depending on tumor size, location, blood supply, and liver function, the interventional radiologist administers a cytotoxic agent and lipiodol emulsion (30 mg lobaplatin, 30 mg pirarubicin, and \< 15 mL lipiodol) through the catheter. Following drug infusion, embolization of the tumor vessels will be routinely performed using gelatin sponge particles.

Intervention Type: PROCEDURE

RFA

Commercial electrode systems are used and the ablation therapy is to be performed according to manufacturer's standard recommendations. All lesions are targeted with CT images during the RFA procedure.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Multiple HCC (2-3 lesions), largest lesion 3-7 cm in diameter, or multiple HCC (4-10 lesions), each ≤ 7 cm in diameter
• No vascular invasion or etrahepatic metastases
• Eastern Cooperative Oncology Group Performance Status 0
• Child-Pugh Stage A or B7
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to procedure:

I.Adequate hematologic function:

1. WBC ≥ 4.0 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)

2. Neutrophils ≥ 1.5 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)

3. Platelets ≥ 60 x 109/L (transfusion to achieve this level is not permitted)

4. Hemoglobin ≥ 100 g/L (may be transfused to meet this requirement)

II.Adequate hepatic function:

1. Serum Aspartate Aminotransferase (AST) ≤ 5×ULN

2. Serum Alanine Aminotransferase (ALT) ≤ 5×ULN

3. Serum total bilirubin ≤ 51.3 μmol/L

4. Serum albumin ≥ 2.8 g/dL

III.Adequate coagulation function:

a)prothrombin activity ≥ 40%

IV.Adequate renal function:

a)Serum creatinine < 110 μmol/L

Exclusion Criteria

• Previous local therapy completed less than 4 weeks prior to the dosing and, if present any related acute toxicity > grade 1
• Any contraindications for TACE/RFA procedure:

I.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 40%) II.Renal failure / insufficiency requiring hemodialysis or peritoneal dialysis. III.Known severe atheromatosis IV.Known uncontrolled blood hypertension (> 160/100 mmHg) V.Patients with known active bleeding (e.g. from GI ulcers, esophageal varices) within 2 months prior to baseline/screening visit or with history or evidence of inherited bleeding diathesis or coagulopathy VI.Clinically significant third space fluid accumulation (i.e., ascites requiring tapping despite use of diuretic or pleural effusion that either required tapping or is associated with shortness of breath)

• Evidence of hepatic discompensation (i.e., refractory ascites, esophageal or gastric variceal bleeding, or hepatic encephalophathy)
• Patients with any other malignancies within the last 3 years before study start
• History of HCC tumor rupture
• Clinically significant (CTC grade 3 or 4) venous or arterial thrombotic disease within past 6 months
• History of abdominal fistula, GI perforation, or intra-abdominal abscess within past 6 months prior to study treatment
• Pregnant women or lactating women
• Be allergic to pirarubicin, lobaplatin and iodized oil

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ming Zhao

OTHER

Sponsor Role: lead

Responsible Party

Ming Zhao

Sun Yat-sen University

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ming Zhao, doctor

Role: PRINCIPAL_INVESTIGATOR

Principal Investigator, Clinical Professor

Locations

Minimally Invasive Interventional Division, Medical Imaging Center, Sun Yat-sen University Cancer Center,

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

2014-FXY-089

Identifier Type: -

Identifier Source: org_study_id