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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05476432
• Other study ID #: SH-5
• Status: Recruiting
• Phase: Phase 3
• Start date: July 26, 2022
• Est. completion date: October 1, 2026

Study information

• Verified date: December 2022
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: October 1, 2026
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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
• FOLFOX 1d
Oxaliplatin, leucovorin, bolus fluorouracil, and infusional fluorouracil 2400 mg/m² over 23 hours

Locations

Country	Name	City	State
China	The First People's Hospital of Foshan	Foshan	Guangdong
China	Cancer Center Sun Yat-sen University	Guangzhou	Guangdong
China	Guangzhou Twelfth People 's Hospita	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Sun Yat-sen University	First People's Hospital of Foshan, Guangzhou No.12 People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	time from randomzation to death	24 months
Secondary	Progression-free survival	time from randomzation to progression or death, which occur firstly.	12 months
Secondary	objective response rate per RECIST 1.1	CR plus PR per RECIST 1.1	12 months
Secondary	Adverse Events	Adverse Events according to CTCAE 4.0	30 days
Secondary	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