Neoadjuvant HAIC for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of resection plus neoadjuvant hepatic arterial infusion chemotherapy (HAIC) compared with resection alone in patients with resectable hepatocellular carcinoma beyond Milan criteria.

Detailed Description
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Resection is the long-term therapeutic option for resectable hepatocellular carcinoma (HCC) patients. While a number of studies demonstrate poor effect and high relapse rate of resection for patients with resectable hepatocellular carcinoma beyond Milan criteria. Our previous prospective study also revealed that neoadjuvant transarterial chemoembolization (TACE) seems to confer a survival benefit for resectable HCC. Recently, the results of our previous prospective study suggested that, compared with TACE, hepatic arterial infusion chemotherapy (HAIC) may improve the survivals for HCC with large HCC.Thus, the investigators carried out this prospective randomized control to demonstrate the superiority of resection plus neoadjuvant HAIC over resection alone.

Official Title
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The Efficacy and Safety of Resection Plus Neoadjuvant Hepatic Arterial Infusion Chemotherapy Compared With Resection Alone in Patients With Resectable Hepatocellular Carcinoma Beyond Milan Criteria

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: FOLFOX
* Procedure: Hepatic resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL; Tumor burden beyond Milan criteria Diagnosed as resectable with consensus by the panel of liver surgery experts; No past history of resection, radiofrequency ablation, TACE, TAI, chemotherapy or molecule-targeted treatment; No Cirrhosis or cirrhotic status of Child-Pugh class A only; Meet the following laboratory parameters:(a) Platelet count ≥ 75,000/μL; (b)Hemoglobin ≥ 8.5 g/dL;(c) Total bilirubin ≤ 30mmol/L;(d) Serum albumin ≥ 32 g/L;(e) ASL and AST ≤ 6 x upper limit of normal;(f) Serum creatinine ≤ 1.5 x upper limit of normal;(g) INR > 2.3 or PT/APTT within normal limits; (h) 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 clinically significant gastrointestinal bleeding within 30 days prior to study entry. Known of serious heart disease which can nor endure the treatment such as cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy 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. Evidence of bleeding diathesis. Any other hemorrhage/bleeding event > CTCAE Grade 3 Serious non-healing wound, ulcer, or bone fracture Known central nervous system tumors including metastatic brain disease Poor compliance that can not comply with the course of treatment and follow up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Resection plus HAIC with FOLFOX<br>Patients receive 4 times of neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX and hepatic resection | Drug: FOLFOX<br>* Hepatic intra-arterial infusion via the tumor feeding arteries of Oxaliplatin , fluorouracil, and leucovorin<br>* Other names: Hepatic Arterial Infusion Chemotherapy of FOLFOX;Procedure: Hepatic resection<br>* R0 resection<br>|
| Active Comparator: Resection<br>Patients receive hepatic resection without neoadjuvant hepatic arterial infusion chemotherapy | Procedure: Hepatic resection<br>* R0 resection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time to death | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Time to recurrence or death | 60 months | 
| Adverse Events | Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.0 | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant hepatic arterial infusion chemotherapy, BCLC A/B, FOLFOX, Resection