Neoadjuvant HAIC for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03469479

Collaborator

(none)

252

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: FOLFOX Procedure: Hepatic resection	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

252 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Efficacy and Safety of Resection Plus Neoadjuvant Hepatic Arterial Infusion Chemotherapy Compared With Resection Alone in Patients With Resectable Hepatocellular Carcinoma Beyond Milan Criteria

Actual Study Start Date :

Mar 2, 2018

Anticipated Primary Completion Date :

Mar 2, 2023

Anticipated Study Completion Date :

Mar 2, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Resection plus HAIC with FOLFOX Patients receive 4 times of neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX and hepatic resection	Drug: FOLFOX Hepatic intra-arterial infusion via the tumor feeding arteries of Oxaliplatin , fluorouracil, and leucovorin Other Names: Hepatic Arterial Infusion Chemotherapy of FOLFOX Procedure: Hepatic resection R0 resection
Active Comparator: Resection Patients receive hepatic resection without neoadjuvant hepatic arterial infusion chemotherapy	Procedure: Hepatic resection R0 resection

Arm

Intervention/Treatment

Experimental: Resection plus HAIC with FOLFOX

Patients receive 4 times of neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX and hepatic resection

Drug: FOLFOX

Hepatic intra-arterial infusion via the tumor feeding arteries of Oxaliplatin , fluorouracil, and leucovorin

Other Names:

Hepatic Arterial Infusion Chemotherapy of FOLFOX

Procedure: Hepatic resection

R0 resection

Active Comparator: Resection

Patients receive hepatic resection without neoadjuvant hepatic arterial infusion chemotherapy

Procedure: Hepatic resection

R0 resection

Outcome Measures

Primary Outcome Measures

Overall survival [60 months]
Time to death

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dongguan People's Hospital	Dongguan	Guangdong	China	523059
2	Cancer Center Sun Yat-sen University	Guangzhou	Guangdong	China	510060
3	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510060
4	Guangzhou Twelfth People's Hospital	Guangzhou	Guangdong	China	510620
5	Kaiping Central Hospital	Kaiping	Guangdong	China	529300
6	The First Affiliated Hospital of University Of South China	Hengyang	Hunan	China	421001
7	First Affiliated Hospital Of Xi'an Jiaotong University	Xi'an	Shanxi	China	710061