HAIC of FOLFOX vs. HAIC of OXA for Advanced HCC

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 hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin compared with HAIC of oxaliplatin alone in patients with hepatocellular carcinoma (HCC) with major portal venous tumor thrombus (PVTT).

Detailed Description
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Sorafenib is the most widely used palliative treatment for hepatocellular carcinoma (HCC) patients with portal venous tumor thrombus (PVTT). Our previous prospective study revealed that sorafenib combined with hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin confer a survival benefit to HCC with major PVTT. However, HAIC of fluorouracil is not such for advanced HCC. Whether HAIC of oxaliplatin is as effective as HAIC of oxaliplatin plus fluorouracil/leucovorin is controversial. Thus, the investigators carried out this prospective randomized control study to find out it.

Official Title
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Sorafenib Plus Hepatic Artery Infusion Chemotherapy of Oxaliplatin, Fluorouracil/Leucovorin Versus Sorafenib Plus Hepatic Artery Infusion Chemotherapy of Oxaliplatin for Hepatocellular Carcinoma With Major Portal Vein Tumor Thrombosis

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Sorafenib
* Drug: HAIC of FOLFOX
* Drug: HAIC of OXA


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) Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria. diagnosed with major or main portal vein invasion (Vp3 or Vp4) KPS≥70； with no previous treatment No Cirrhosis or cirrhotic status of Child-Pugh class A only Not amendable to surgical resection ,local ablative therapy and any other cured treatment. The following laboratory parameters: Platelet count ≥ 75,000/µL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 30 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: 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. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Evidence of bleeding diathesis. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug Serious non-healing wound, ulcer, or bone fracture Known central nervous system tumors including metastatic brain disease

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sorafenib plus HAIC of FOLFOX<br>Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin, Fluorouracil and Leucovorin | Drug: Sorafenib<br>* Oral Sorafenib, 400mg, Bid<br>Drug: HAIC of FOLFOX<br>* administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries<br>* Other names: Oxaliplatin , fluorouracil, and leucovorin;|
| Experimental: Sorafenbi plus HAIC of OXA<br>Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin | Drug: Sorafenib<br>* Oral Sorafenib, 400mg, Bid<br>Drug: HAIC of OXA<br>* administration of Oxaliplatin via the tumor feeding arteries<br>* Other names: Oxaliplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress free survival | Progress free survival | 10 months | 
| Adverse Events | Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.0 | 30 days | 
| Number of of Patients developed Adverse Events | Number of of patients who developed adverse event. Postoperative adverse events were graded based on CTCAE v4.0 | 30 days | 
| Tumor response | overall response | 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Hepatic arterial infusion chemotherapy, Sorafenib, Oxaliplatin plus Fluorouracil/Leucovorin, Oxaliplatin