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

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma Non-Resectable
• Intervention / Treatment: Drug: cisplatin and 5-fluorouracil

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of
    • Not yet recruiting
    • Korea University Ansan Hospital
    • Contact: Yim, MD., PhD.
  • Bucheon, Korea, Republic of
    • Not yet recruiting
    • Sooncheonhyang University Hospital Bucheon
    • Contact: Kim, MD., PhD.
  • Bucheon, Korea, Republic of
    • Not yet recruiting
    • The Catholic University Of Korea Bucheon St. Mary's Hospital
    • Contact: Lee, MD., PhD.
  • Daegu, Korea, Republic of
    • Not yet recruiting
    • Keimyung University Dongsan Medical Center
    • Contact: Chung, MD., PhD.
  • Daejeon, Korea, Republic of
    • Not yet recruiting
    • The Catholic University of Korea Daejeon ST. Mary's hospital
    • Contact: Song, MD., PhD.
  • Hwasun, Korea, Republic of
    • Not yet recruiting
    • Chonnam National University Hwasun Hospital
    • Contact: Cho, MD., PhD.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Seoul National University Hospital
    • Contact: Yoon, MD., PhD.
  • Seoul, Korea, Republic of
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
    • Contact: Si Hyun Bae, MD., PhD.
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Korea University Anam Hospital
    • Contact: Seo, MD., PhD.
  • Seoul, Korea, Republic of
    • Recruiting
    • Sooncheonhyang University Hospital Seoul
    • Contact: Jang, MD., PhD.
  • Suwon, Korea, Republic of
    • Recruiting
    • Ajou University Hospital
    • Contact: Wang, MD., PhD.
    • Contact: Cheong, MD., PhD.
  • Suwon, Korea, Republic of
    • Not yet recruiting
    • The Catholic University Of Korea St. Vincent's Hospital
    • Contact: Song, MD., PhD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cisplatin and 5-fluorouracil; 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; 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); Other Names: CBD-01 and CBD-02

What is the study measuring?

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	Time Frame
Time-to-Progression	Approximately 24 months
Progression-free-survival	Approximately 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory endpoint: Diagnostic performance of biomarkers	Patients will be categorized according to the result of biomarker expression and then AUC value of ROC curve analysis will be evaluated as an exploratory endpoint to assess predictive performance of biomarkers for therapeutic response of drugs.	Through study completion, an average of 3 months

Collaborators and Investigators

• Sponsor: CbsBioscience
• Investigators: Principal Investigator: Si Hyun Bae, MD., PhD., The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: November 10, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 13, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cisplatin; Fluorouracil
• Other Study ID Numbers: CBS-PCT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED