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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05476432

Collaborator

Guangzhou No.12 People's Hospital (Other), First People's Hospital of Foshan (Other)

300

Enrollment

Locations

Arms

50.2

Anticipated Duration (Months)

100

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Procedure: HAIC Drug: FOLFOX 2d Drug: FOLFOX 1d	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 26, 2022

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Oct 1, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall survival [24 months]

Secondary Outcome Measures

Progression-free survival [12 months]
objective response rate per RECIST 1.1 [12 months]
Adverse Events [30 days]
the predictive power of thymidylate synthase (TYMS) [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First People's Hospital of Foshan	Foshan	Guangdong	China	510060
2	Cancer Center Sun Yat-sen University	Guangzhou	Guangdong	China	510060
3	Guangzhou Twelfth People 's Hospita	Guangzhou	Guangdong	China	510620