HAIC of Oxaliplatin, and 2400 mg/m² 5-fu vs HAIC of Oxaliplatin, and 1200 mg/m² 5-fu for Unresectable HCC: a Randomised Phase 3 Non-inferiority Trial

Hepatic Artery Infusion of Oxaliplatin, Leucovorin, and 2400 mg/m² Fluorouracil Versus Hepatic Artery Infusion of Oxaliplatin, Leucovorin, and 1200 mg/m² Fluorouracil for Unresectable Hepatocellular Carcinoma: a Randomised Phase 3 Non-inferiority Trial

Hepatic artery infusion of oxaliplatin, leucovorin and 2400 mg/m² fluorouracil is effective in hepatocellular carcinoma. However, SILIUS study showed that sorafenib plus hepatic artery infusion of cisplatin and fluorouracil did not significantly improve overall survival compared with sorafenib alone. Whether fluorouracil is effevtive is known.

Study Overview

• Status: Unknown
• Conditions: HepatoCellular Carcinoma
• Intervention / Treatment: Drug: 2400 mg/m² 5-fu; Drug: 1200 mg/m² 5-fu

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510620
      • Recruiting
      • Guangzhou Twelfth People 's Hospita
      • Principal Investigator: YuanMin Zhou, MD
    • Kaiping, Guangdong, China, 529300
      • Recruiting
      • Kaiping Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).
• 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 past history of TACE, HAIC, chemotherapy or molecule-targeted treatment;
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5-fu 2400	Drug: 2400 mg/m² 5-fu; Hepatic arterial infusion of oxaliplatin,leucovorin and 2400 mg/m² 5-FU
Experimental: 5-fu 1200	Drug: 1200 mg/m² 5-fu; Hepatic arterial infusion of oxaliplatin,leucovorin and 1200 mg/m² 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
progression-free survival	24 months
objective response rate	6 months
Adverse Events	30 Days after HAIC
disease control rate	6 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Guangzhou No.12 People's Hospital; Kaiping Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): December 14, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Hepatic arterial infusion chemotherapy; 2400 mg/m² 5-fu; 1200 mg/m² 5-fu
• 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; Fluorouracil
• Other Study ID Numbers: SH-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No