Therapeutic Effect of Ethanol-gelfoam Mixture for the Treatment of Arterioportal Shunts (APS) in Patients With HCC

Study Overview
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Brief Summary
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Transcatheter arterial chemoembolization (TACE) is a key palliative treatment for patients with inoperable hepatocellular carcinoma (HCC). Arterioportal shunts (APS) can aggravate portal hypertension and the shunts let lipiodol flow to normal liver tissue and result in poor Lipiodol deposition in the tumor, causing liver ischemia. Occlusion of APS is a vital and initial step for the following embolization of tumor. Ethanol-gelfoam mixture(EGM) and gelfoam only both can occlude APS in patients with hepatocellular carcinoma (HCC). The aim of this study was to evaluate the efficacy and safety of EGM in treatment of APS in the procedure of TACE, and to analyze the prognostic factors for survival in this kind of patients.

Official Title
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A Randomized Controlled Trial of Ethanol-gelfoam Mixture(EGM) Versus Gelfoam for the Treatment of Arterioportal Shunts (APS) in Patients With Hepatocellular Carcinoma (HCC) Treated With Transarterial Chemoembolization (TACE)

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Procedure: TACE
* Drug: EGM
* Drug: PVA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 Child-Pugh A or B cirrhosis ECOG performance status Grade 2 or below No serious concurrent medical illness No prior treatment (including surgery) for HCC Histologically or cytologically proven HCC (an alphafetoprotein level > 500 ug/ml in the presence of radiological findings suggestive of HCC in a patient with chronic HBV or HCV infection can be considered eligible at investigator's discretion) Unresectable and locally advanced disease without extra-hepatic disease Massive expansive or nodular tumor morphology with measurable lesion on CT Size of largest tumor <= 15cm in largest dimension Number of main tumor <= 5, excluding associated small satellite lesions Arterioportal shunts (APS) is found in the angiography of HCC blood supply Exclusion Criteria: History of prior malignancy except skin cancer History of significant concurrent medical illness such as ischemic heart disease or heart failure History of acute tumor rupture Serum creatinine level > 180 umol/L Presence of biliary obstruction not amenable to percutaneous drainage Child-Pugh C cirrhosis History of hepatic encephalopathy, or Intractable ascites not controllable by medical therapy, or History of variceal bleeding within last 3 months, or Serum total bilirubin level > 50 umol/L, or Serum albumin level < 28g/L, or INR > 1.3 Presence of extrahepatic metastasis Predominantly infiltrative lesion Diffuse tumor morphology with extensive lesions involving both lobes. Hepatic artery thrombosis, or Partial or complete thrombosis of the main portal vein, or Tumor invasion of portal branch of contralateral lobe, or Hepatic vein tumor thrombus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TACE+EGM<br>Occlude APS with EGM and perform TACE sequentially | Procedure: TACE<br>* Transarterial chemoembolisation (TACE)<br>Drug: EGM<br>* Occlude arterioportal shunts(APS) with ethanol/gelfoam mixture(EGM)<br>|
| Active Comparator: TACE+PVA<br>Occlude APS with PVA and perform TACE sequentially | Procedure: TACE<br>* Transarterial chemoembolisation (TACE)<br>Drug: PVA<br>* Occlude arterioportal shunts(APS) with PVA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | Defined as time (in days) from time of TACE non-eligibility to death due to any cause, and will be evaluated every 8 weeks in the protocol treatment, and every one year in the follow-up period, respectively. Patients lost to follow-up or alive at the end of the study will be censored at the last date known to be alive. | 3 years | 
| APS improvement | Changes of Arterioportal Shunts Treated with PVA or EGM | 2 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time To Progression | Time from randomization to radiological progression. Definition of progression is based on the mRECIST criteria. Deaths during follow-up without evidence of radiological progression are censored. | every 8 weeks, upto 3 years from date of randomization | 
| progression free survival | Time from randomization to either radiological progression or death. Patients alive and free of progression at the end of follow-up are censored. | every 8 weeks, upto 3 years from date of randomization | 
| Response Rate | Definition of response is based on the mRECIST criteria. | every 8 weeks, upto 3 years from date of randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Arterioportal shunts, Transarterial Chemoembolization, Ethanol, Gelfoam, Polyvinyl Alcohol Foam Embolization Particles (PVA)