Liver Resection Versus Transarterial Chemoembolization for the Treatment of Intermediate-stage Hepatocellular Carcinoma

NCT ID: NCT02755311

Last Updated: 2016-04-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 198 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2016-06-30

Brief Summary

The role of transarterial chemoembolization (TACE) as the standard therapy for intermediate-stage hepatocellular carcinoma (HCC) is being challenged by increasing studies which showed that liver resection (LR) is a safe and feasible procedure with better survival outcomes than TACE does.

In light of this, the investigators have constructed a Markov model to simulate comparing LR and TACE in the treatment of intermediate-stage HCC. The results suggested that LR may provide survival benefit over TACE for the treatment of intermediate-stage HCC in cirrhotic patients. However, validating the simulated result by a study with higher quality (e.g. prospective clinical trial) would be of great value in providing a more convincing finding. Therefore, based on the established Markov model, the investigators aimed to prospectively compare the treatment efficacy and safety of LR with TACE for consecutive patients with intermediate-stage HCC.

Detailed Description

Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide and the third most frequent cause of death of cancer. However, the management strategies for intermediate-stage HCC remain controversial without global consensus. On one hand, Barcelona Clinic Liver Cancer (BCLC) staging system recommends liver resection (LR) for very early and early-stage HCC, and transarterial chemoembolization (TACE) for intermediate-stage HCC. On the other hand, observational studies in both Eastern and Western countries have emerged to suggest that LR was safe and achieved better survival than TACE for patients with intermediate-stage HCC, but only very few studies have been conducted to directly compare LR with TACE for these patients.

In light of this, the investigators have conducted a multistate Markov model simulating a randomized clinical trial comparing LR with TACE over a follow-up period of 15 years. The results suggested that LR may provide survival benefit over TACE for the treatment of intermediate-stage HCC in cirrhotic patients. However, validating the simulated result by a study with higher quality (e.g. prospective clinical trial) would be of great value in providing a more convincing finding.Therefore, based on the established Markov model,the investigators aimed to prospectively compare the treatment efficacy and safety of LR with TACE for consecutive patients with intermediate-stage HCC.

Conditions

Hepatocellular Carcinoma

Study Design

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

Study Groups

liver resection

Resection was carried out under general anesthesia using a right subcostal incision with a midline extension. Intra-operative ultrasonography was performed routinely to evaluate the tumor burden, liver remnant and the possibility of a negative resection margin. The investigators performed anatomical resection aiming at a resection margin of at least 1 cm. Pringle's maneuver was routinely used with a clamp and unclamp time of 10 minutes and 5 minutes, respectively. Hemostasis of the raw liver surface was done with suturing and application of fibrin glue.

Group Type: EXPERIMENTAL

liver resection

Intervention Type: PROCEDURE

Intraoperative ultrasound was routinely used during surgery. Anatomic resection was carried out in the form of segmentectomy or/and subsegmentectomy.In segmentectomy, the hepatic parenchyma was transacted at the intersegmental plane as described by Couinaud. If the hepatic parenchymal transaction plane needed to go beyond the intersegmental plane to achieve the desired extent of resection margin, the small portal branches supplying the liver parenchyma up to the intended transaction plane were punctured under US guidance and injected with methylthioninium chloride, and then liver subsegmentectomy was performed either alone or in combination with segmentectomy along the plane of demarcation as delineated by the injected methylthioninium chloride. Nonanatomic resection with a negative resection margin was performed when anatomical resection may cause inadequate liver remnant. Pringle's maneuver was used if necessary with a clamp/unclamp time of 10 min/5 min.

transarterial chemoembolization

A microcatheter was inserted into the feeding arteries as selectively as possible through the lobar, segmental, or subsegmental arteries, dependent on the tumor distribution and hepatic functional reserve. Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin. Subsequently, chemolipiodolization was performed mixed with 5 ml of lipiodol. According to the number and size of the lesions, and liver and kidney function of the patient, the chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team. If residual flow remained after infusion of these agents, additional lipiodol was injected. Embolization was performed with absorbable gelatin sponge particles 350-560 μm in diameter.

Group Type: ACTIVE_COMPARATOR

transarterial chemoembolization

Intervention Type: PROCEDURE

A microcatheter was inserted into the feeding arteries as selectively as possible through the lobar, segmental, or subsegmental arteries, dependent on the tumor distribution and hepatic functional reserve. Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin. Subsequently, chemolipiodolization was performed mixed with 5 ml of lipiodol. According to the number and size of the lesions, and liver and kidney function of the patient, the chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team. If residual flow remained after infusion of these agents, additional lipiodol was injected. Embolization was performed with absorbable gelatin sponge particles 350-560 μm in diameter.

carboplatin

Intervention Type: DRUG

Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin (Bristol-Myers Squibb, New York, NY).

lipiodol

Intervention Type: DRUG

Chemolipiodolization was performed mixed with 5 ml of lipiodol (Lipiodol Ultra-Fluide; André Guerbet Laboratories, Aulnay-sous-Bois, France).

epirubicin , pirarubicin , hydroxycamptothecin and fluorouracil

Intervention Type: DRUG

The chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team.

absorbable gelatin sponge particles

Intervention Type: OTHER

Embolization was performed with absorbable gelatin sponge particles (Gelfoam; Hangzhou Bi-Trumed Biotech Co., Ltd., Hangzhou, Zhejiang, China) 350-560 μm in diameter.

Interventions

liver resection

Intraoperative ultrasound was routinely used during surgery. Anatomic resection was carried out in the form of segmentectomy or/and subsegmentectomy.In segmentectomy, the hepatic parenchyma was transacted at the intersegmental plane as described by Couinaud. If the hepatic parenchymal transaction plane needed to go beyond the intersegmental plane to achieve the desired extent of resection margin, the small portal branches supplying the liver parenchyma up to the intended transaction plane were punctured under US guidance and injected with methylthioninium chloride, and then liver subsegmentectomy was performed either alone or in combination with segmentectomy along the plane of demarcation as delineated by the injected methylthioninium chloride. Nonanatomic resection with a negative resection margin was performed when anatomical resection may cause inadequate liver remnant. Pringle's maneuver was used if necessary with a clamp/unclamp time of 10 min/5 min.

Intervention Type: PROCEDURE

transarterial chemoembolization

A microcatheter was inserted into the feeding arteries as selectively as possible through the lobar, segmental, or subsegmental arteries, dependent on the tumor distribution and hepatic functional reserve. Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin. Subsequently, chemolipiodolization was performed mixed with 5 ml of lipiodol. According to the number and size of the lesions, and liver and kidney function of the patient, the chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team. If residual flow remained after infusion of these agents, additional lipiodol was injected. Embolization was performed with absorbable gelatin sponge particles 350-560 μm in diameter.

Intervention Type: PROCEDURE

carboplatin

Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin (Bristol-Myers Squibb, New York, NY).

Intervention Type: DRUG

lipiodol

Chemolipiodolization was performed mixed with 5 ml of lipiodol (Lipiodol Ultra-Fluide; André Guerbet Laboratories, Aulnay-sous-Bois, France).

Intervention Type: DRUG

epirubicin , pirarubicin , hydroxycamptothecin and fluorouracil

The chemotherapeutic agents, including epirubicin (50-100 mg), pirarubicin (30-50 mg), hydroxycamptothecin (10-30 mg) and fluorouracil (500-1000 mg), were determined by the multidisciplinary team.

Intervention Type: DRUG

absorbable gelatin sponge particles

Embolization was performed with absorbable gelatin sponge particles (Gelfoam; Hangzhou Bi-Trumed Biotech Co., Ltd., Hangzhou, Zhejiang, China) 350-560 μm in diameter.

Intervention Type: OTHER

Other Intervention Names

Hepatectomy; chemoembolization through artery; TACE; a drug derived from cisplatin; epirubicin，pirarubicin，hydroxycamptothecin or fluorouracil

Eligibility Criteria

Inclusion Criteria

• age between 18 and 75 years
• 2 to 3 lesions with at least one >3 cm in diameter; or more than 3 lesions of any diameter
• Child-Pugh A/B liver function
• no previous treatment
• an Eastern Cooperative Oncology Group performance status of 0

Exclusion Criteria

• radiologic or pathological evidence of vascular invasion or extrahepatic metastases
• severe coagulopathy (prothrombin activity <40% or a platelet count of<40,000/mm3)
• evidence of hepatic decompensation including refractory ascites, esophageal or gastric variceal bleeding, or hepatic encephalopathy
• obstructive jaundice
• an American Society of Anesthesiologists score of 3 or more
• present or past history of any other concurrent malignancies
• complicated with other severe diseases such as chronic kidney disease, cardiovascular disease, auto-immunological disease, etc
• contraindications to carboplatin, epirubicin, mitomycin, or lipiodol

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

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Ming Kuang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Zhenwei Peng, MD

Role: primary

pengzhenwei2005@163.com

Other Identifiers

HCC 006

Identifier Type: -

Identifier Source: org_study_id