HAIC With One-day FOLFOX vs. HAIC With Two-day FOLFOX for Unresectable HCC: a Non-inferiority Study

Hepatic Arterial Infusion With Oxaliplatin & 23h Fluorouracil Versus Hepatic Arterial Infusion With Oxaliplatin & 46h Fluorouracil for Unresectable Hepatocellular Carcinoma：a Non-inferiority Study

Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin&5-fluorouracil was effective in unresectable hepatocellular carcinoma (HCC). The program of FOLFOX-HAIC in HCC was performed for 1 day (HAIC 1d) or 2 days (HAIC 2d). We hereby retrospectively compared the efficacy and safety between these two treatment regimens, and explored the predictive power of thymidylate synthase (TYMS), an enzyme involved in the DNA synthesis process and metabolism of fluorouracil. Patients with HCC staged BCLC A-B receive HAIC only, and patients with HCC staged BCLC C receive HAIC plus systemic treatment, such as sorafenib, A+T, lenvatinib.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: HAIC; Drug: FOLFOX 1d; Drug: FOLFOX 2d

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China, 510060
      • Recruiting
      • The First People's Hospital of Foshan
      • Contact: HuanWei Chen; Phone Number: 15626470388; Email: 1547463629@qq.com
    • 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

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), simultaneously staged as BCLC A, BCLC B or BCLC C based on Barcelona Clinic Liver Cancer staging system.
• 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 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
• Serious non-healing wound, ulcer, or bone fracture
• Known central nervous system tumors including metastatic brain disease
• Poor compliance that can not comply with the course of treatment and follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAIC 1d; Oxaliplatin, leucovorin, and bolus fluorouracil were conducted equally in the both groups, while infusional fluorouracil 2400 mg/m² was given over 23 hours in the HAIC 1d group	Procedure: HAIC; The microcatheter was advanced into the hepatic artery, and patients were transferred to the inpatient ward for drug infusion via the hepatic artery; Drug: FOLFOX 1d; Oxaliplatin, leucovorin, bolus fluorouracil, and infusional fluorouracil 2400 mg/m² over 23 hours
Active Comparator: HAIC 2d; Oxaliplatin, leucovorin, and bolus fluorouracil were conducted equally in the both groups, while infusional fluorouracil 2400 mg/m² was given over 46 hours in the HAIC 2d group	Procedure: HAIC; The microcatheter was advanced into the hepatic artery, and patients were transferred to the inpatient ward for drug infusion via the hepatic artery; Drug: FOLFOX 2d; Oxaliplatin, leucovorin, bolus fluorouracil, and infusional fluorouracil 2400 mg/m² over 46 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	time from randomzation to death	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	time from randomzation to progression or death, which occur firstly.	12 months
objective response rate per RECIST 1.1	CR plus PR per RECIST 1.1	12 months
Adverse Events	Adverse Events according to CTCAE 4.0	30 days
the predictive power of thymidylate synthase (TYMS)	the correlation between thymidylate synthase (TYMS) and survival. Whether the survival of patients with low TYMS is better than those with high TYMS	12 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First People's Hospital of Foshan; Guangzhou No.12 People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2022
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 27, 2022

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

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; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin
• Other Study ID Numbers: SH-5

Drug and device information, study documents

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