Evaluation of Hepatic Arterial Infusion of Cisplatin and 5-FU in Biomarker Stratified HCC

Study Overview
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Brief Summary
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This study is to assess the efficacy and the safety of hepatic arterial infusion of cisplatin and 5-fluorouracil (HAIC) in advanced HCC patients stratified by biomarker expression predicting therapeutic response.

Detailed Description
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Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and 5-fluorouracil has been used in advanced HCC. However, cisplatin or 5-fluorouracil acts on cells without tumor selectivity. Therefore, to improve the tumor selectivity and effectiveness of HAIC, molecular subtyping-based stratification strategies should be considered. In this study, patients who have progressed or intolerance to sorafenib with non-metastatic HCC in TNM stage III-IVA and ECOG PS 0 or 1, Child-Pugh class A will be enrolled. 96 patients with pre-treatment tumor biopsy will receive Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h on days 1-3) through implanted port system. This treatment will be repeated every 4 weeks, up to 6 times. The primary objective is to determine overall response rate, where benefit is defined as complete or partial response according to mRECIST V1.1. Secondary endpoints include time to progression, progression free survival. The biopsy tissue will be subjected to real time reverse transcriptase polymerase chain reaction for quantification of gene expression levels. Patients will be categorized into two groups according to gene expression results, and then AUC value of ROC curve analysis will be evaluated as an exploratory endpoint to assess predictive performance of biomarker for therapeutic response of HAIC.

Official Title
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Single-arm, Prospective, Multicenter Clinical Trial to Assess the Efficacy and the Safety of Combination Therapy of Hepatic Arterial Infusion of Cisplatin and 5-FU in Advanced Hepatocellular Carcinoma With Low Expression of HMGB2 Biomarker

Conditions
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Hepatocellular Carcinoma Non-Resectable

Intervention / Treatment
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* Drug: cisplatin and 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: over 20 years old Patients with advanced hepatocellular carcinoma who have progressed or intolerance to Sorafenib Patients with advanced hepatocellular carcinoma who cannot be treated with surgery, transplantation, RFA, or TACE. TNM stage III/IV (including intrahepatic single or multiple tumors without extrahepatic metastasis regardless of lymph node metastasis) ECOG performance status of 0 or 1 Liver function status of Child-Pugh Class A or B more than 3 months of life expectancy serum creatinine <1.5 mg/dL aminotransferase <5 times the upper limit of normal absolute neutrophil count >1,500 cells/lL platelet count >75,000/lL hemoglobin >10 g/dL Exclusion Criteria: patients with extrahepatic tumors Patients requiring combined treatment with chemotherapy, radiotherapy, TACE, RFA, or others Patients in any severe and/or uncontrolled medical conditions patients with history of allergic response to CT contrast media patients who participated as subjects in other interventional clinical studies (as of the date of visit) within 60 days before drug administration Any person deemed inappropriate by reason of the investigator for other reasons

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cisplatin and 5-fluorouracil<br>Enrolled patients with pre-treatment tumor biopsy will receive Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h on days 1-3) through implanted port system. This treatment will be repeated every 4 weeks, up to 6 times. | Drug: cisplatin and 5-fluorouracil<br>* Hepatic arterial infusion of Cisplatin (60mg/m2 for 2h on day 2) and 5-fluorouracil (500mg/m2 for 5h on days 1-3) through implanted port system (chemoport)<br>* Other names: CBD-01 and CBD-02;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response | Objective tumor response according to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) assessed by radiological review | Approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-Progression |  | Approximately 24 months | 
| Progression-free-survival |  | Approximately 24 months |