HAIC Plus PD-1 Antibody vs HAIC Plus Sorafenib for Advanced HCC

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with Programmed Cell Death Protein-1 (PD-1) antibody compared with HAIC plus sorafenib in patients with advanced hepatocellular carcinoma (HCC)

Detailed Description
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The results of our preliminary pilot study suggested that sorafenib combined with hepatic arterial infusion chemotherapy (HAIC) may improve the survivals for advanced hepatocellular (HCC). Programmed Cell Death Protein-1 (PD-1) antibody has been proved effective and safety for advanced HCC. There is no study about HAIC plus PD-1 antibody. Thus, the investigators carried out this prospective randomized control study to compare HAIC plus sorafenib and HAIC plus PD-1 antibody.

Official Title
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Hepatic Artery Infusion Chemotherapy Plus Programmed Cell Death Protein-1 (PD-1) Antibody vs Hepatic Artery Infusion Chemotherapy Plus Sorafenib for Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: HAIC
* Drug: PD-1 antibody
* Drug: Sorafenib


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. Barcelona clinic liver cancer-stage C Major portal vein tumor thrombus (Vp3,Vp4) Eastern Cooperative Oncology Group performance status of 0 to 1 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. 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: HAIC plus PD-1 antibody<br>Participants received PD-1 antibody intravenously and hepatic artery infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. | Procedure: HAIC<br>* administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks<br>Drug: PD-1 antibody<br>* 200mg intravenously every 3 weeks<br>* Other names: Programmed cell death 1 antibody;|
| Active Comparator: HAIC plus sorafenib<br>Participants received sorafenib capsules 400mg bid in continuous 21-day treatment cycles, and received hepatic artery infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. | Procedure: HAIC<br>* administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks<br>Drug: Sorafenib<br>* 400 mg Bid Po<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), or date of death, whichever occurred first. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff. | 12 months | 
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on RECIST. | 12 months | 
| Adverse Events | Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03 | 12 months | 

 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, Programmed cell death protein-1 antibody, Oxaliplatin, 5-Fluorouracil and Leucovorin