Hepatectomy Versus Chemoembolization for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

Hepatic Resection Versus Transarterial Chemoembolization as the Initial Treatment for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

The purpose of this study is to compare the survival outcomes between hepatic resection and transarterial lipiodol chemoembolization (TACE) used as the initial treatment in patients with Resectable Hepatocellular Carcinoma Beyond Milan Criteria.

Study Overview

• Status: Unknown
• Conditions: Resectable Hepatocellular Carcinoma Beyond Milan Criteria
• Intervention / Treatment: Procedure: Immediate Resection; Procedure: Chemoembolization and Response-Dependent Resection

Detailed Description

For patients with large/multiple, and resectable hepatocellular carcinomas (HCCs) without macrovascular invasion or extrahepatic spread, the choice of treatment remains largely controversial. For these patients, transarterial lipiodol chemoembolization (TACE) is recommended as a palliative therapy.

On the other hand, many authors still believe that hepatic resection is the only potential curative treatment in these patients because it is still feasible to remove all macroscopic tumors safely at surgery. With advances in surgical techniques, more large/multiple HCCs are now resectable, and long-term results have been reported that ranged from 30% to 58% at 5 years; even patients with large bilobar multiple HCC could reach a survival rate of more than 20% at 5 years after hepatic resection.

Until now, there have been only a few studies that compared the outcomes of hepatic resection and TACE in the treatment of multiple HCCs, and these have reported controversial results. Some studies showed that hepatic resection had survival benefi t over TACE, but other studies showed the opposite result ( 11-15 ). Therefore, the investigators performed this prospective study in consecutive patients with large/multiple, and resectable HCCs to compare the outcomes in patients who underwent hepatic resection or TACE as the initial treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 436
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ming Shi, MD; Phone Number: 86-2087343154; Email: shiming@mail.sysu.edu.cn
• Study Contact Backup: Name: Rong Ping Guo, MD; Phone Number: 86-2087342266; Email: guorongp@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University
      • Contact: Ming Shi, MD; Phone Number: 86-2087343115; Email: shiming@mail.sysu.edu.cn

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:

• A diagnosis of HCC based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL).
• The patient has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation.
• The tumor beyound milan criteria.
• The tumor was evaluated to be resectable by a same group of surgeon.
• Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria
• No serious concurrent medical illness
• Not pregnant or breast-feeding patients
• Cirrhotic status of Child-Pugh class A only

• The following laboratory parameters:

  • Platelet count ≥ 80,000/µL
  • Hemoglobin ≥ 8.5 g/dL
  • Total bilirubin ≤ 1.5 mg/dL Serum albumin ≥ 35 g/L
  • ASL and AST ≤ 5 x upper limit of normal
  • Serum creatinine ≤ 1.5 x upper limit of normal
  • INR ≤ 1.5 or PT/APTT within normal limits
  • Absolute neutrophil count (ANC) >1,500/mm3
• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Tumor vascular invasion or distant metastases
• Significant renal impairment (creatinine clearance < 30 mL/minute) or patients on dialysis
• On anticoagulation or suffering from a known bleeding disorder
• Unstable coronary artery disease or recent MI
• Known history of HIV
• History of organ allograft
• Known or suspected allergy to the investigational agents or any agent given in association with this trial.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
• Serious non-healing wound, ulcer, or bone fracture
• Known central nervous system tumors including metastatic brain disease
• severe Arterioportal Shunts or Arteriavein Shunts

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate Resection; patients received immediate surgical hepatic resection	Procedure: Immediate Resection; patients received immediate surgical resection.
Experimental: Chemoembolization and Response-Dependent Resection; patients underwent transarterial chemoembolization (TACE) as initial treatments, and only patients who showed good response were subjected to surgical resection.	Procedure: Chemoembolization and Response-Dependent Resection; patients underwent transarterial chemoembolization (TACE) as initial treatments, and only patients who showed good response were subjected to surgical resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival time	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease free survival		5 years
Number of Adverse Events	All severe adverse events for the entire course of treatment, including treatment for primary tumor and recurrent tumor.	30 days

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Third Affiliated Hospital, Sun Yat-Sen University; First People's Hospital of Chenzhou; Kaiping Central Hospital; Dongguan Shi People's Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): August 2, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Milan Criteria
• 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: HCC_S012