Neoadjuvant HAIC for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

Phase 3

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: FOLFOX; Procedure: Hepatic resection

• Registration Number: NCT03469479
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of resection plus neoadjuvant hepatic arterial infusion chemotherapy (HAIC) compared with resection alone in patients with resectable hepatocellular carcinoma beyond Milan criteria.

Detailed Description

Resection is the long-term therapeutic option for resectable hepatocellular carcinoma (HCC) patients. While a number of studies demonstrate poor effect and high relapse rate of resection for patients with resectable hepatocellular carcinoma beyond Milan criteria. Our previous prospective study also revealed that neoadjuvant transarterial chemoembolization (TACE) seems to confer a survival benefit for resectable HCC. Recently, the results of our previous prospective study suggested that, compared with TACE, hepatic arterial infusion chemotherapy (HAIC) may improve the survivals for HCC with large HCC.Thus, the investigators carried out this prospective randomized control to demonstrate the superiority of resection plus neoadjuvant HAIC over resection alone.

Study Timeline

• Study Start: 2018-03-02
• Study First Submitted: 2018-03-11
• Study First Submitted QC: 2018-03-15
• Study First Posted: 2018-03-19
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-31
• Last Update Posted: 2018-08-02
• Primary Completion: 2023-03-02
• Study Completion: 2023-03-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 252

Inclusion Criteria

• The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL;

• Tumor burden beyond Milan criteria

• Diagnosed as resectable with consensus by the panel of liver surgery experts;

• No past history of resection, radiofrequency ablation, TACE, TAI, 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

• 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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Resection plus HAIC with FOLFOX	Hepatic resection	Patients receive 4 times of neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX and hepatic resection
Resection plus HAIC with FOLFOX	FOLFOX	Patients receive 4 times of neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX and hepatic resection
Resection	Hepatic resection	Patients receive hepatic resection without neoadjuvant hepatic arterial infusion chemotherapy

Primary Outcome Measures

Name	Time	Method
Overall survival	60 months	Time to death

Secondary Outcome Measures

Name	Time	Method
Disease-free survival	60 months	Time to recurrence or death
Adverse Events	30 days	Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.0

Trial Locations

Locations (7)

Dongguan People's Hospital; 🇨🇳 Dongguan, Guangdong, China

Cancer Center Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Guangzhou Twelfth People's Hospital; 🇨🇳 Guangzhou, Guangdong, China

Kaiping Central Hospital; 🇨🇳 Kaiping, Guangdong, China

The First Affiliated Hospital of University Of South China; 🇨🇳 Hengyang, Hunan, China

First Affiliated Hospital Of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shanxi, China