The Efficacy and Safety of Retreatment With TAI for Patients Who Showed TACE-resistant: a Randomized Controlled Trial

Study Overview
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Brief Summary
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Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, any treatment guidelines do not specify the criteria for repeating TACE. The study,conducted in Europe ，recently published in the journal of Hepatology shows the ART score of >=2.5 prior the second TACE identifies patients with a dismal prognosis who may not profit from further TACE sessions. However,in clinical practice，we also found some patients who showed TACE-resistant at the beginning of treatment may access to get objective response of retreatment with transcatheter arterial infusion (TAI). So the investigators conduct this prospective,randomized controlled study to find out whether the patient who showed TACE-resistant can obtain survival benefit from retreatment with TAI.

Detailed Description
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Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology.This suggests that not all patients with intermediate-stage HCC will derive similar benefit from transcatheter arterial infusion (TAI), and that some patients may benefit from other treatment options. Repetition of TACE is based on evidence suggesting that one cycle of TACE may not be sufficient for effective treatment of intermediate-stage HCC and repeating TACE prolongs survival. However, intermediate-stage HCC patients often have unsatisfactory clinical outcomes with repeated TACE and there is not sufficiently addressed by existing guidelines include the criteria for repeating TACE and recommendations about the number of TACE cycles to be repeated before switching to another or no treatment.The study,recently published in the journal of Hepatology shows the ART score of >=2.5 prior the second TACE identifies patients with a dismal prognosis who may not profit from further TACE sessions.In clinical practice，however, we also found some patients who showed TACE-resistant at the beginning of treatment may access to get objective response of retreatment with TAI. So we conduct this prospective,randomized controlled study to find out whether the patient who showed TACE-resistant can obtain survival benefit from retreatment with TAI.

Official Title
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The Efficacy and Safety of Retreatment With Transcatheter Arterial Infusion (TAI) for Patients Who Showed TACE-resistant: a Randomized Controlled Trial

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: TAI of FOLFOX
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients， > 18 years and <=70 years old diagnosed with HCC according to the European Association for the Study of the Liver (EASL) diagnostic criteria The patient has received 2 session of TACE TACE failure/refractoriness by Liver Cancer Study Group of Japan (LCSGJ) criteria Cirrhotic status of Child-Pugh class A The following laboratory parameters: Platelet count ≥ 60,000/µL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 1.5 mg/dL Serum albumin ≥ 35 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 Ability to understand the protocol and to agree to and sign a written informed consent document Exclusion Criteria: Patients with complete response (CR) after the first TACE did not receive a further TACE session Eastern Cooperative Oncology Group (ECOG) >1 Known history of HIV History of organ allograft Known or suspected allergy to the investigational agents or any agent given in association with this trial. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Serious non-healing wound, ulcer, or bone fracture Evidence of bleeding diathesis. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug Severe Arterioportal Shunts or Arteriavein Shunts Known metastatic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: TAI of FOLFOX<br>Retreatment With Transcatheter arterial infusion of oxaliplatin , fluorouracil, and leucovorin | Procedure: TAI of FOLFOX<br>* Retreatment with TAI: administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries<br>* Other names: Transcatheter arterial infusion of oxaliplatin , fluorouracil, and leucovorin;|
| Active Comparator: Sorafenib<br>treatment with sorafenib | Drug: Sorafenib<br>* Accept sorafenib.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | All severe adverse events for the entire course of treatment | 30 days | 
| overall survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, TACE, TACE failure, TACE refractoriness, TAI, Sorafenib