Adjuvant TACE to Reduce the HCC Recurrence After Resection

The Clinical Randomized Trial of Adjuvant Transarterial Chemo Embolization (TACE) to Reduce the Recurrence in Hepatocellular Carcinoma (HCC) Patients at High Risk After Resection

Hepatocellular carcinoma (HCC) is the sixth most common malignancies worldwide and the second leading cause of cancer-related death. Surgical resection is still the main radical approach for HCC, but the recurrence rate after hepatectomy is very high, which hampers the further improvement of prognosis of HCC patients. The conventional risk factors of recurrence including: huge tumor, multiple lesions, vessels invasion and tumor rupture. Recently, the microvessels invasion (MVI) has been recognized a novel risk factor of recurrence after hepatectomy. The investigators' previous study showed that the recurrence rate is more than 50% for the patients with >5cm solitary tumor and MVI. The MVI was confirmed as the only independent risk factor for the overall and disease-free survival of HCC patients in multiple variables analysis. It is important to reduce the recurrence and prolong the survival of patients after hepatectomy with effective adjuvant therapy. TACE has been utilized as an adjuvant therapy after hepatectomy, but its significance is still unknown. Then, the investigators design the current prospective randomized clinical trial to evaluate the effect of adjuvant TACE to reduce the recurrence in HCC patients at high risk (>5cm solitary tumor and MVI) after resection, compared to vigilant follow-up.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Procedure: Adjuvant TACE; Procedure: Follow-up

Detailed Description

The patients with solitary tumor more than 5cm and microvessels invasion after radical hepatectomy were randomized to receive adjuvant TACE（1~2 cycles, 4~6 weeks) or follow-up. The main endpoint: overall survival (OS), disease-free survival(DFS), and safety were compared between this two groups.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18~75 years;
2. Eastern Cooperative Oncology Group performance status (ECOG PS) score <=2;
3. Histologically confirmed hepatocellular carcinoma with microvessels invasion;
4. No previous treatment for HCC;
5. More than 5 cm solitary tumor before surgery confirmed by more than 2 radiological examinations;
6. R0 resection achieved;
7. No recurrence evidence in radiological follow-up 3~7 weeks after surgery;
8. Adequate hematologic parameters and liver and kidney functions: (1) Neutrophils Absolute >=1.5*10^9/L; (2) Hemoglobin >=90g/L; (3) Platelet count >=75*10^9/L; (4) Serum albumin >=35g/L; (5) Serum total bilirubin <=1.5* upper limit of normal (ULN); (6) Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) <2.5*ULN; (7) Serum creatinine <=1.5*ULN; (8) International normalized ratio (INR) <=1.5;
9. Give signed informed consent before enrollment.

Exclusion Criteria:

1. Function impairment of vital organs (heart, lung, kidney, etc), serious infection or >grade 2 adverse events (Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0);
2. Histologically confirmed of positive resection margin (R1 resection);
3. Previous or current malignant tumor beyond HCC;
4. Allergy to any agent of the TACE regimen;
5. History of organ transplantation;
6. Previously receiving other treatments for HCC;
7. Pregnant or breastfeeding women, and women of childbearing potential without adequate contraception;
8. Neurological or mental abnormalities that may affect cognitive assessment and inform consent;
9. Concomitant anti-tumor therapy or participating in other interventional clinical trials;
10. Other psychological, family or social reason, which would affect compliance with the study protocol.

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
Experimental: Adjuvant TACE; Adjuvant TACE were performed 4-6 weeks after surgery	Procedure: Adjuvant TACE; 1~2 cycles TACE were performed as adjuvant therapy after radical hepatectomy
Other: Follow-up; Routine follow-up were performed instead of adjuvant TACE	Procedure: Follow-up; Patients received just follow-up to monitor the recurrence of HCC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The overall survival is defined as the percentage of patients who are alive at 5 years after their enrollments of this study.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	The disease-free survival is defined as the percentage of patients who are alive at 5 years without any signs or symptoms of HCC after their enrollments of this study.	5 years
Safety: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Rong-Ping Guo, M.D., Sun Yat-sen University

Publications and helpful links

General Publications

• Zhong C, Guo RP, Li JQ, Shi M, Wei W, Chen MS, Zhang YQ. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol. 2009 Oct;135(10):1437-45. doi: 10.1007/s00432-009-0588-2. Epub 2009 May 1.
• Li JQ, Zhang YQ, Zhang WZ. [Evaluation of chemoembolization as an adjuvant therapy for primary liver carcinoma after surgical resection]. Zhonghua Zhong Liu Za Zhi. 1994 Sep;16(5):387-9. Chinese.
• Li JQ, Zhang YQ, Zhang WZ, Yuan YF, Li GH. Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy. J Cancer Res Clin Oncol. 1995;121(6):364-6. doi: 10.1007/BF01225689.
• Peng B, Liang L, He Q, Zhou F, Luo S. Surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus. Hepatogastroenterology. 2006 May-Jun;53(69):415-9.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 23, 2016
• First Submitted That Met QC Criteria: June 1, 2016
• First Posted (Estimate): June 2, 2016

Study Record Updates

• Last Update Posted (Estimate): June 20, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Carcinoma,Hepatocellular; Hepatocellular; Chemoembolization; Adjuvant therapy; Microvessels invasion
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence
• Other Study ID Numbers: SYSUCC-HCC-ADTACE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No