HAIC of Oxaliplatin, and 2400 mg/m² 5-fu vs HAIC of Oxaliplatin, and 1200 mg/m² 5-fu for Unresectable HCC: a Randomised Phase 3 Non-inferiority Trial

Study Overview
=================
Brief Summary
-----------------
Hepatic artery infusion of oxaliplatin, leucovorin and 2400 mg/m² fluorouracil is effective in hepatocellular carcinoma. However, SILIUS study showed that sorafenib plus hepatic artery infusion of cisplatin and fluorouracil did not significantly improve overall survival compared with sorafenib alone. Whether fluorouracil is effevtive is known.

Official Title
-----------------
Hepatic Artery Infusion of Oxaliplatin, Leucovorin, and 2400 mg/m² Fluorouracil Versus Hepatic Artery Infusion of Oxaliplatin, Leucovorin, and 1200 mg/m² Fluorouracil for Unresectable Hepatocellular Carcinoma: a Randomised Phase 3 Non-inferiority Trial

Conditions
-----------------
HepatoCellular Carcinoma

Intervention / Treatment
-----------------
* Drug: 2400 mg/m² 5-fu
* Drug: 1200 mg/m² 5-fu


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age range from 18-75 years; KPS≥70; 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; Diagnosed as unresectable with consensus by the panel of liver surgery experts; No past history of TACE, HAIC, 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 within 4 weeks of first dose of study drug

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5-fu 2400<br> | Drug: 2400 mg/m² 5-fu<br>* Hepatic arterial infusion of oxaliplatin,leucovorin and 2400 mg/m² 5-FU<br>|
| Experimental: 5-fu 1200<br> | Drug: 1200 mg/m² 5-fu<br>* Hepatic arterial infusion of oxaliplatin,leucovorin and 1200 mg/m² 5-FU<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | 24 months | 
| objective response rate |  | 6 months | 
| disease control rate |  | 6 months | 
| Adverse Events |  | 30 Days after HAIC | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatic arterial infusion chemotherapy, 2400 mg/m² 5-fu, 1200 mg/m² 5-fu