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

NCT02435953 | Completed Phase 3 DMC

• 1 other identifier: 2014-FXY-089
• Study Type: interventional
• Target: 241
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (PFS-R)

  From the date of randomization to the date of occurrence of radiologic disease progression as determined according to the RECIST v1.1, or death (by any cause), whichever occurs first, assessed up to 10 years.

Secondary Outcomes (6)

• Overall survival (OS)

  From the date of randomization to the date of death (due to any cause), assessed up to 10 years.

• Progression-free survival (PFS) according to HCC modified RECIST (PFS-m)

  From the date of randomization to the date of occurrence of radiologic disease progression as determined according to the HCC modified RECIST, or death (by any cause), whichever occurs first, assessed up to 10 years.

• unAblation-TACEable or unTACEable progression-free survival (uAT-PFS)

  From the date of randomization to the date of the following untreatable progression or death by any cause, assessed up to 10 years.

• Objective response rate (ORR) according to mRECIST (ORR-m)

  From date of randomization until the date of study completion, an average of 8 months.

• Disease control rate (DCR) according to mRECIST (DCR-m)

  From date of randomization until the date of study completion, an average of 8 months.

Other Outcomes (3)

• Time to advanced-stage (TTAS)

  From randomization to disease progression to Barcelona Clinic Liver Cancer stage C (BCLC-C), assessed up to 10 years.

• Time to extrahepatic spread (TTEHS)

  From randomization to occurrence of extrahepatic metastasis, assessed up to 10 years.

• Time to macrovascular invasion (TTMVI)

  From randomization to occurrence of macrovascular invasion, assessed up to 10 years.

Study Arms (2)

TACE-RFA

EXPERIMENTAL

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

Procedure: TACE; Procedure: RFA

TACE alone

ACTIVE COMPARATOR

On-demand TACE.

Procedure: TACE

Interventions

TACE 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.

TACE alone; TACE-RFA

RFA 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-RFA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• WBC ≥ 4.0 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
• Neutrophils ≥ 1.5 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
• Platelets ≥ 60 x 109/L (transfusion to achieve this level is not permitted)
• Hemoglobin ≥ 100 g/L (may be transfused to meet this requirement)
• II.Adequate hepatic function:
• Serum Aspartate Aminotransferase (AST) ≤ 5×ULN
• Serum Alanine Aminotransferase (ALT) ≤ 5×ULN
• Serum total bilirubin ≤ 51.3 μmol/L
• Serum albumin ≥ 2.8 g/dL

You may not qualify if:

• 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

Sponsors & Collaborators

• Ming Zhao: lead

Study Sites (1)

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

Guangzhou, Guangdong, 500060, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Ming Zhao, doctor

  Principal Investigator, Clinical Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sun Yat-sen University

Study Record Dates

• First Submitted: May 3, 2015
• First Posted: May 6, 2015
• Study Start: May 1, 2015
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

CN (1)