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Neoadjuvant HAIC for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

Primary Purpose

Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
FOLFOX
Hepatic resection
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Neoadjuvant hepatic arterial infusion chemotherapy, BCLC A/B, FOLFOX, Resection

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Dongguan People's HospitalRecruiting
  • Cancer Center Sun Yat-sen UniversityRecruiting
  • The First Affiliated Hospital of Sun Yat-sen UniversityRecruiting
  • Guangzhou Twelfth People's HospitalRecruiting
  • Kaiping Central HospitalRecruiting
  • The First Affiliated Hospital of University Of South ChinaRecruiting
  • First Affiliated Hospital Of Xi'an Jiaotong UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Resection plus HAIC with FOLFOX

Resection

Arm Description

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

Patients receive hepatic resection without neoadjuvant hepatic arterial infusion chemotherapy

Outcomes

Primary Outcome Measures

Overall survival
Time to death

Secondary Outcome Measures

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

Full Information

First Posted
March 11, 2018
Last Updated
July 31, 2018
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT03469479
Brief Title
Neoadjuvant HAIC for Resectable Hepatocellular Carcinoma Beyond Milan Criteria
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Unknown status
Study Start Date
March 2, 2018 (Actual)
Primary Completion Date
March 2, 2023 (Anticipated)
Study Completion Date
March 2, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Neoadjuvant hepatic arterial infusion chemotherapy, BCLC A/B, FOLFOX, Resection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
252 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Resection plus HAIC with FOLFOX
Arm Type
Experimental
Arm Description
Patients receive 4 times of neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX and hepatic resection
Arm Title
Resection
Arm Type
Active Comparator
Arm Description
Patients receive hepatic resection without neoadjuvant hepatic arterial infusion chemotherapy
Intervention Type
Drug
Intervention Name(s)
FOLFOX
Other Intervention Name(s)
Hepatic Arterial Infusion Chemotherapy of FOLFOX
Intervention Description
Hepatic intra-arterial infusion via the tumor feeding arteries of Oxaliplatin , fluorouracil, and leucovorin
Intervention Type
Procedure
Intervention Name(s)
Hepatic resection
Intervention Description
R0 resection
Primary Outcome Measure Information:
Title
Overall survival
Description
Time to death
Time Frame
60 months
Secondary Outcome Measure Information:
Title
Disease-free survival
Description
Time to recurrence or death
Time Frame
60 months
Title
Adverse Events
Description
Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.0
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ming Shi, MD
Phone
(8620)-87343938
Email
shiming@sysu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
RongPing Guo, MD
Phone
(8620)-87342266
Email
guorp@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ming Shi, MD
Organizational Affiliation
The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dongguan People's Hospital
City
Dongguan
State/Province
Guangdong
ZIP/Postal Code
523059
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wusheng Yu, MD
Phone
13827285010
Email
yuwusheng1998@126.com
Facility Name
Cancer Center Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming Shi, MD
Phone
8620-87343115
Email
shiming@mail.sysu.edu.cn
Facility Name
The First Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guosheng Tan, MD
Phone
13725254145
Email
tgs1976@163.com
Facility Name
Guangzhou Twelfth People's Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510620
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuanmin Zhou, MD
Phone
15521278919
Email
13430288977@139.com
First Name & Middle Initial & Last Name & Degree
Jinghua Chen, MD
Facility Name
Kaiping Central Hospital
City
Kaiping
State/Province
Guangdong
ZIP/Postal Code
529300
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shijie Zhang, MD
Phone
13717287622
Email
Shijie_9262511@163.com
Facility Name
The First Affiliated Hospital of University Of South China
City
Hengyang
State/Province
Hunan
ZIP/Postal Code
421001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaoping Wu, MD
Phone
13975486015
Email
wxp19730806@sina.com
Facility Name
First Affiliated Hospital Of Xi'an Jiaotong University
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710061
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xin Zheng, MD
Phone
13649265446
Email
183421344@qq.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Neoadjuvant HAIC for Resectable Hepatocellular Carcinoma Beyond Milan Criteria

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