Sorafenib or Lenvatinib Plus HAIC of 130 mg/m² Oxaliplatin, and 5-fu vs Sorafenib or Lenvatinib Plus HAIC of 85mg/m² Oxaliplatin, and 5-fu for Unresectable Advanced HCC: a Randomised Phase 3 Trial

Study Overview
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Brief Summary
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A randomized trial showed that sorafenib plus hepatic artery infusion of 85mg/m² oxaliplatin, leucovorin and fluorouracil is more effective than sorafenib in advanced hepatocellular carcinoma. However, a retrospective study showed that hepatic artery infusion of 130 mg/m² oxaliplatin, leucovorin and fluorouracil is more effective than sorafenib in advanced hepatocellular carcinoma. It is unknown which oxaliplatin dose is better.

Official Title
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Sorafenib or Lenvatinib Plus Hepatic Artery Infusion of 130 mg/m² Oxaliplatin, Leucovorin, and Fluorouracil Versus Sorafenib or Lenvatinib Plus Hepatic Artery Infusion of 85 mg/m² Oxaliplatin, Leucovorin, and 1200 mg/m² Fluorouracil for Unresectable Advanced Hepatocellular Carcinoma: a Randomised Phase 3 Trial

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: HAIC of 130 mg/m² Oxaliplatin, and 5-fu
* Drug: HAIC of 85 mg/m² Oxaliplatin, and 5-fu
* Drug: TKI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; With vascular invasion or extrahepatic metastasis 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
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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 |
| --- | --- |
| Experimental: OXA 130<br>Patients received sorafenib or lenvatinib Plus HAIC of 130 mg/m² oxaliplatin, and 2400 mg/m² 5-fu | Drug: HAIC of 130 mg/m² Oxaliplatin, and 5-fu<br>* Hepatic arterial infusion of 130 mg/m² oxaliplatin,leucovorin and 2400 mg/m² 5-FU<br>Drug: TKI<br>* sorafenib 400mg bid or lenvatinib 12 mg/day (for bodyweight ≥60 kg) or 8 mg/day (for bodyweight <60 kg)<br>|
| Active Comparator: OXA 85<br>Patients received sorafenib or lenvatinib Plus HAIC of 85 mg/m² oxaliplatin, and 2400 mg/m² 5-fu | Drug: HAIC of 85 mg/m² Oxaliplatin, and 5-fu<br>* Hepatic arterial infusion of 85 mg/m² oxaliplatin,leucovorin and 2400 mg/m² 5-FU<br>Drug: TKI<br>* sorafenib 400mg bid or lenvatinib 12 mg/day (for bodyweight ≥60 kg) or 8 mg/day (for bodyweight <60 kg)<br>|

What is the study measuring?
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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 | 
| time to response | time to the date that patients achieved objective response | 12 months | 
| Adverse Events |  | 30 Days after HAIC |