Neoadjuvant HAIC for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: FOLFOX; Procedure: Hepatic resection

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 Type: Interventional
• Enrollment (Anticipated): 252
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: RongPing Guo, MD; Phone Number: (8620)-87342266; Email: guorp@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Dongguan, Guangdong, China, 523059
      • Recruiting
      • Dongguan People's Hospital
      • Contact: Wusheng Yu, MD; Phone Number: 13827285010; Email: yuwusheng1998@126.com
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: Guosheng Tan, MD; Phone Number: 13725254145; Email: tgs1976@163.com
    • Guangzhou, Guangdong, China, 510620
      • Recruiting
      • Guangzhou Twelfth People's Hospital
    • Kaiping, Guangdong, China, 529300
      • Recruiting
      • Kaiping Central Hospital
  • Hunan
    • Hengyang, Hunan, China, 421001
      • Recruiting
      • The First Affiliated Hospital of University of South China
      • Contact: Xiaoping Wu, MD; Phone Number: 13975486015; Email: wxp19730806@sina.com
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • Recruiting
      • First Affiliated Hospital of Xi'an JiaoTong University
      • Contact: Xin Zheng, MD; Phone Number: 13649265446; Email: 183421344@qq.com

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:

• 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.

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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time to death	60 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Ming Shi, MD, The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2018
• Primary Completion (Anticipated): March 2, 2023
• Study Completion (Anticipated): March 2, 2023

Study Registration Dates

• First Submitted: March 11, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 2, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: FOLFOX; Neoadjuvant hepatic arterial infusion chemotherapy; BCLC A/B; Resection
• 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
• Other Study ID Numbers: HCC-180302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No