Optimal Treatment on Hepatocellular Carcinoma (HCC) With Cirrhotic Portal Hypertension

A Randomized Control Clinical Trial Between Precise Hepatectomy and Combined Interventional Treatment on Hepatocellular Carcinoma (HCC) With Cirrhotic Portal Hypertension

There is no consensus about the optimal treatment of hepatocellular carcinoma (HCC) with cirrhotic portal hypertension, While this group of patients are classified as hepatectomy contraindication according to guidelines from National Comprehensive Cancer Network (NCCN) and American Association for the Study of Liver Diseases (AASLD). With improvement of surgical technique, preoperative evaluation, and perioperative management,especially the Precise Hepatectomy Technique, more and more studies confirmed the safety of surgical intervention to hepatocellular carcinoma (HCC) patients with cirrhotic portal hypertension.However, most of the previous studies were either retrospective or with small samples.

The investigators project is a prospective randomized controlled trial, planning to compare the safety, efficacy and quality of life between precise hepatectomy and combined interventional treatment on hepatocellular carcinoma (HCC) with cirrhotic portal hypertension, to make a further understanding of optimal strategy.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma(HCC); Cirrhotic Portal Hypertension
• Intervention / Treatment: Procedure: Precise hepatectomy; Other: Combined intervention (chemoembolization/ablation)

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

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 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of hepatocellular carcinoma patients, in accordance with HCC Professional Committee of the Chinese Anti-Cancer Association 2001 "Clinical Diagnosis of Primary Liver Cancer and Staging Criteria"
• solitary tumor ≤5cm, or three or fewer lesions none ≤3cm，As Milan criteria
• History of hepatitis B or HBsAg positive
• Cirrhosis and portal hypertension
• No treatment on liver cancer before
• KPS score ≥ 70
• The age of 18 to 65 years
• Child-Pugh A or B (Class B, scoring no more than 7 points)

• Baseline laboratory test comply with the following criteria:

  • White blood cell ≥ 1.0×109/L
  • Platelet ≥ 25×109/L
  • Hemoglobin ≥ 80g/L
  • Serum ALT,AST ≤ 3×upper limit of normal (ULN)
  • Serum creatinine ≤ 1.5 × ULN
  • INR<1.5, or prothrombin time <ULN +4 sec
  • Albumin ≥30g/L
  • Total bilirubin ≤34mmol/L
• Informed consent with signature and time
• Good patient compliance

• The surgical group patients received radical hepatectomy. Radical surgery is defined as: complete resection of visible tumor, R0 resection margins, and also including:

  • The number of tumors is less than 3
  • No tumor thrombus found in major branch of the portal veins, hepatics, inferior vena cava or bile duct
  • No hepatic hilar lymph node metastasis
  • No extrahepatic metastasis

Exclusion Criteria:

• extrahepatic metastasis; With metastasis in major branch of portal vein, hepatic vein
• History of hepatitis C or HCV-Ab positive
• Pugh Child-Pugh C, or with massive ascites or had a history of hepatic encephalopathy, or Upper digestive tract bleeding
• Poor physical condition or cachexia
• During the past 12 months just before the study, there had been any of the following: myocardial infarction, severe/unstable angina, coronary artery bypass graft surgery, congestive heart failure, cerebrovascular accident (including transient ischemic attack), pulmonary embolism; arrhythmia according to the NCI-CTCAE ≥ grade 2, QTc interval extension (male> 450 ms, female> 470 ms);
• Renal insufficiency, need peritoneal dialysis or hemodialysis
• Serious dysfunction of other organs
• History of second primary malignant tumors
• Known or new evidence of brain or leptomeningeal disease
• Hemophilia or bleeding tendency, and are taking therapeutic doses of coumarin derivative anticoagulant therapy drugs
• Pregnant or lactation, all female patients with childbearing potential must have a pregnancy test (serum or urine) within 7 days after enrollment,and the result is negative
• History of organ transplantation
• Known HIV infection
• With any other serious acute and chronic physical or mental disease or abnormal laboratory tests, which are likely to increase risks or interfere with the interpretation of the results, or researchers believe that patients are not suitable for enrollment

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: surgery; Precise hepatectomy	Procedure: Precise hepatectomy; Precise hepatectomy
Active Comparator: combined intervention; transcatheter hepatic arterial chemoembolization and/or ablation	Other: Combined intervention (chemoembolization/ablation); transcatheter hepatic arterial chemoembolization and/or ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is based on death from any cause, not just the condition being treated, thus it picks up death from side effects of the treatment, and effects on survival after relapse	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment complication	defined as complications within the 90 days after treatment	90 days
Time to progress(TTP)	TTP: The Hazard Ratio will be analyzed respectively with 95% confidence interval. Meanwhile, Kaplan-Meier estimation and survival curves will be performed.	3 years
Disease control rate(DCR)	Disease control rate: Calculate the disease control rate of the two treatment groups (disease control rate) and its 95% confidence interval, and make a descriptive analysis.	3 years
Quality of life(Qol)	Quality of life: Follow the QOL-LC V2.0	5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): December 30, 2018
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 16, 2012
• First Posted (Estimate): July 17, 2012

Study Record Updates

• Last Update Posted (Actual): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: safety; hepatocellular carcinoma; portal hypertension; cirrhotic; precise hepatectomy; combined interventional treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Hypertension; Carcinoma; Carcinoma, Hepatocellular; Hypertension, Portal
• Other Study ID Numbers: 20125010Y