HAIC With One-day FOLFOX vs. HAIC With Two-day FOLFOX for Unresectable HCC: a Non-inferiority Study

Study Overview
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Brief Summary
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Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin&5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens, and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil. Patients with HCC staged BCLC A-B receive HAIC only, and patients with HCC staged BCLC C receive HAIC plus systemic treatment, such as sorafenib, A+T, lenvatinib.

Official Title
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Hepatic Arterial Infusion With Oxaliplatin & 23h Fluorouracil Versus Hepatic Arterial Infusion With Oxaliplatin & 46h Fluorouracil for Unresectable Hepatocellular Carcinoma：a Non-inferiority Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: HAIC
* Drug: FOLFOX 2d
* Drug: FOLFOX 1d


Participation Criteria
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Eligibility Criteria
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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), simultaneously staged as BCLC A, BCLC B or BCLC C based on Barcelona Clinic Liver Cancer staging system. 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 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 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: HAIC 1d<br>Oxaliplatin, leucovorin, and bolus fluorouracil were conducted equally in the both groups, while infusional fluorouracil 2400 mg/m² was given over 23 hours in the HAIC 1d group | Procedure: HAIC<br>* The microcatheter was advanced into the hepatic artery, and patients were transferred to the inpatient ward for drug infusion via the hepatic artery<br>Drug: FOLFOX 1d<br>* Oxaliplatin, leucovorin, bolus fluorouracil, and infusional fluorouracil 2400 mg/m² over 23 hours<br>|
| Active Comparator: HAIC 2d<br>Oxaliplatin, leucovorin, and bolus fluorouracil were conducted equally in the both groups, while infusional fluorouracil 2400 mg/m² was given over 46 hours in the HAIC 2d group | Procedure: HAIC<br>* The microcatheter was advanced into the hepatic artery, and patients were transferred to the inpatient ward for drug infusion via the hepatic artery<br>Drug: FOLFOX 2d<br>* Oxaliplatin, leucovorin, bolus fluorouracil, and infusional fluorouracil 2400 mg/m² over 46 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | time from randomzation to death | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | time from randomzation to progression or death, which occur firstly. | 12 months | 
| objective response rate per RECIST 1.1 | CR plus PR per RECIST 1.1 | 12 months | 
| Adverse Events | Adverse Events according to CTCAE 4.0 | 30 days | 
| the predictive power of thymidylate synthase (TYMS) | the correlation between thymidylate synthase (TYMS) and survival. Whether the survival of patients with low TYMS is better than those with high TYMS | 12 months |