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

Hepatocellular Carcinoma Clinical Trial

Official title:

Liver Resection Versus Transarterial Chemoembolization for the Treatment of Intermediate-stage Hepatocellular Carcinoma: a Prospective Non-randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02755311
• Other study ID #: HCC 006
• Status: Recruiting
• Phase: Phase 3
• First received: April 3, 2016
• Last updated: April 27, 2016
• Start date: March 2014
• Est. completion date: June 2016

Study information

• Verified date: April 2016
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 198
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• 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.
• 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.

Drug:
• carboplatin
Hepatic artery infusion chemotherapy was performed using 300 mg carboplatin (Bristol-Myers Squibb, New York, NY).
• lipiodol
Chemolipiodolization was performed mixed with 5 ml of lipiodol (Lipiodol Ultra-Fluide; André Guerbet Laboratories, Aulnay-sous-Bois, France).
• 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.

Other:
• 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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	1-year overall survival	1 year	No
Secondary	Mortality	1-month mortality	1 month	No