Phase Ⅱ Study of HAIC of FOLFOX vs. Sorafenib in HCC Refractory to TACE

Study Overview
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Brief Summary
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To evaluate safety and efficacy of combined hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin and sorafenib in hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization(TACE)

Detailed Description
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In most current guidelines, sorafenib is considered as the second-line treatment for patients with transarterial chemoembolization(TACE) failure or refractoriness.However,the median overall survival of those treated with sorafenib monotherapy was 16.4 to 24.7 months. Whether combining sorafenib with hepatic arterial infusion chemotherapy(HAIC) of oxaliplatin,5-fluorouracil and leucovorin is safe, well tolerated, and efficacious remains unknown, with no prospective clinical data currently available.The investigators therefore conducted a prospective and randomized phase II trial to compare the safety and efficacy of HAIC with sorafenib in patients refractory to TACE

Official Title
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Randomized Phase Ⅱ Study of Second-line Treatment Comparing Hepatic Arterial Infusion Chemotherapy of Oxaliplatin, 5-fluorouracil and Leucovorin With Sorafenib in Hepatocellular Carcinoma Refractory to Transarterial Chemoembolization

Conditions
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Hepatocellular Carcinoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: TACE failure or refractoriness based on the Liver Cancer Study Group of Japan (LCSGJ) criteria, including appearance of vascular invasion or two or more consecutive insufficient responses of the intrahepatic lesion; Except for TACE, patients have received no previous anti-tumor treatment; The diagnosis of HCC was based on histological results; Patients must have at least one tumor lesion that can be accurately measured; Not amendable to surgical resection ,local ablative therapy and any other cured treatment; No Cirrhosis or cirrhotic status of Child-Pugh class A only; No liver protection therapy in 2 weeks before enrolled, and 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 ≤ 5 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: 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; 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAIC of FOLFOX<br>Hepatic arterial infusion chemotherapy with oxaliplatin, leucovorin, and 5-fluorouracil | Drug: HAIC of FOLFOX<br>* administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries<br>* Other names: Oxaliplatin , fluorouracil, and leucovorin;|
| Active Comparator: Sorafenib<br>Sorafenib 400 mg orally twice a day | Drug: Sorafenib<br>* administration of Sorafenib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The period from the date of the start of HAIC or sorafenib until the date of the confirmation of tumor progression or death | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The period from the date of the start of HAIC or sorafenib until the date of the confirmation of tumor progression or death | 12 months | 
| Adverse Events | Postoperative adverse events were graded based on CTCAE v4.03 | 30 Days after HAIC and TACE | 
| Objective response rate | Best response based on mRECIST | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic arterial infusion chemotherapy, Sorafenib