Phase II Study of HAIC Using Cisplatin,Leucovorin and 5-Fluorouracil

Study Overview
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Brief Summary
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The purpose of this phase II study is to determine the recommended dose, as well as the safety and efficacy of the combination of oxaliplatin, leucovorin and 5-Fu introduced by hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC).

Detailed Description
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The results of our preliminary pilot study suggested that the combination of oxaliplatin, leucovorin and 5-Fu introduced by hepatic arterial infusion chemotherapy (HAIC) may improve the survivals for advanced stage HCC. Thus, the investigators carried out this prospective randomized control study to determine the recommended dose as well as the safety and efficacy.

Official Title
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Phase II Study of Hepatic Arterial Infusion Chemotherapy Using Oxaliplatin,Leucovorin and 5-Fluorouracil

Conditions
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HepatoCellular Carcinoma

Intervention / Treatment
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* Drug: 5-Fu, oxaliplatin , leucovorin
* Drug: 5-Fu, oxaliplatin , leucovorin
* Drug: 5-Fu, oxaliplatin , leucovorin


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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Full Dosage<br>Full Dosage Chemotherapy regimen administered by HAI | Drug: 5-Fu, oxaliplatin , leucovorin<br>* Drug: 5-Fu, oxaliplatin and regular dose of leucovorin Regimen: (1) 5-Fu: 2800 mg/m2 (2) oxaliplatin: 135 mg/m2 (3) leucovorin: 400mg/m2<br>* Other names: Full dose Folfox;|
| Experimental: Low Dosage of 5-Fu<br>Low Dose of 5-Fu Chemotherapy regimen administered by HAI | Drug: 5-Fu, oxaliplatin , leucovorin<br>* Drug: 5-Fu, oxaliplatin and regular dosage of leucovorin Regimen: (1) 5-Fu: 1400 mg/m2 (2) oxaliplatin: 135 mg/m2 (3) leucovorin: 400mg/m2<br>* Other names: Low dose 5-Fu Folfox;|
| Experimental: Low Dosage of oxaliplatin<br>Low Dose of oxaliplatin Chemotherapy regimen administered by HAI | Drug: 5-Fu, oxaliplatin , leucovorin<br>* Drug: 5-Fu, oxaliplatin and regular dosage of leucovorin Regimen: (1) 5-Fu: 2800 mg/m2 (2) oxaliplatin: 85 mg/m2 (3) leucovorin: 400mg/m2<br>* Other names: Low dose oxaliplatin Folfox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | Tumor response evaluated by postoperative CT/MRI scan according to RECIST criteria. | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03 | 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 v4.03 | 30 days | 

 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, optimal dose