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TACE+RFA Versus Re-resection for Recurrent Small Hepatocellular Carcinoma (TACE-RFA)

Primary Purpose

Hepatocellular Carcinoma, Surgery, Ablation

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
TACE+RFA
re-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 hepatocellular carcinoma, repeat hepatectomy, radiofrequency ablation, transcatheter arterial chemoembolization

Eligibility Criteria

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

Inclusion Criteria:

  1. age 18 - 75 years;
  2. recurrence of HCC 12 months after initial hepatectomy;
  3. no other treatment received except for the initial hepatectomy;
  4. Single tumor≤5cm in diameter; or 2-3 lesions each ≤ 3.0 cm
  5. lesions visible on ultrasound and with an acceptable and safe path between the lesion and the skin as shown on ultrasound;
  6. no severe coagulation disorders (prothrombin activity < 40% or a platelet count of < 40,000 / mm3;
  7. Eastern Co-operative Oncology Group performance(ECOG) status 0 -1

Exclusion Criteria:

  1. the presence of vascular invasion or extrahepatic spread on imaging;
  2. a Child-Pugh class C liver cirrhosis or evidence of hepatic decompensation including ascites, severe coagulation disorders (prothrombin activity < 40% or a platelet count of < 40,000 / mm3), esophageal or gastric variceal bleeding or hepatic encephalopathy;
  3. an American Society of Anesthesiologists (ASA) score ≥ 3 -

Sites / Locations

  • Sun Yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TACE+RFA

re-resection

Arm Description

TACE was performed according to the following protocol: All patients underwent a distal super-selective catheterization of the hepatic arteries using a coaxial technique and micro-catheters (2.9 Fr, Terumo Corporation, Tokyo, Japan). Then, the same three chemotherapeutic agents at the same dosages were used throughout this study, regardless of tumor number and size. Hepatic artery infusion chemotherapy was performed using carboplatin 300 mg. After that, chemolipiodolization was performed using epirubicin 50 mg, and mitomycin C 8 mg mixed with 5 mL of lipiodol. If the territory of the chemolipiodolized artery did not show stagnant flow, pure lipiodol was then injected. RFA was performed after TACE in 2 months by using a commercially available system (RF 2000; Radio-Therapeutics Mountain View, CA), and a needle electrode with a 15 Ga insulated cannula with 10 hook-shaped expandable electrode tines with a diameter of 3.5 cm at expansion (LeVeen; RadioTherapeutics).

Re-resection was carried out under general anesthesia using a right subcostal incision with a midline extension. Intra-operative ultrasonography was performed routinely to evaluate the tumor burden, liver remnant and the possibility of a negative resection margin. We performed anatomical resection aiming at a resection margin of at least 1 cm. Pringle's maneuver was routinely used with a clamp and unclamp time of 10 minutes and 5 minutes, respectively. Hemostasis of the raw liver surface was done with suturing and application of fibrin glue.

Outcomes

Primary Outcome Measures

overall survival

Secondary Outcome Measures

disease-free survival

Full Information

First Posted
April 5, 2013
Last Updated
April 12, 2013
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT01833286
Brief Title
TACE+RFA Versus Re-resection for Recurrent Small Hepatocellular Carcinoma
Acronym
TACE-RFA
Official Title
Radiofrequency Ablation Combined With Transcatheter Arterial Chemoembolization Versus Re-resection for Recurrent Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Unknown status
Study Start Date
July 2013 (undefined)
Primary Completion Date
July 2017 (Anticipated)
Study Completion Date
July 2019 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Partial hepatectomy is still considered as the conventional therapy for HCC. Intrahepatic recurrence of HCC after partial hepatectomy is common and was reported to be more than 77% within 5 years after surgery. Repeat hepatectomy is an effective treatment for intrahepatic HCC recurrence, with a 5-year survival rate of 19.4-56%. This is comparable to the survival after initial hepatectomy for HCC. Unfortunately, repeat hepatectomy could be carried out only in a small proportion of patients with HCC recurrence (10.4-31%), either because of the poor functional liver reserve or because of widespread intrahepatic recurrence. In the past two decades, percutaneous radiofrequency ablation (PRFA) has emerged as a new treatment modality and has attracted great interest because of its effectiveness and safety for small HCC (≤ 5.0 cm). Studies using PRFA to treat recurrent HCC after partial hepatectomy reported a 3-year survival rate of 62-68%, which is comparable to those achieved by surgery. PRFA is particularly suitable to treat recurrent HCC after partial hepatectomy because these tumors are usually detected when they are small and PRFA causes the least deterioration of liver function in the patients. Our previous retrospective study demonstrated that RFA was comparable to re-resection for recurrent HCC, and our recent RCT showed that RFA combined with TACE is superior to RFA for HCC ≤7.0cm. So our hypothesis is that RFA combined with TACE is superior to re-resection for recurrent small HCC. The aim of this retrospective study is to compare the outcome of reresection with TACE+RFA for small recurrent HCC after partial hepatectomy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Surgery, Ablation
Keywords
hepatocellular carcinoma, repeat hepatectomy, radiofrequency ablation, transcatheter arterial chemoembolization

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
TACE+RFA
Arm Type
Experimental
Arm Description
TACE was performed according to the following protocol: All patients underwent a distal super-selective catheterization of the hepatic arteries using a coaxial technique and micro-catheters (2.9 Fr, Terumo Corporation, Tokyo, Japan). Then, the same three chemotherapeutic agents at the same dosages were used throughout this study, regardless of tumor number and size. Hepatic artery infusion chemotherapy was performed using carboplatin 300 mg. After that, chemolipiodolization was performed using epirubicin 50 mg, and mitomycin C 8 mg mixed with 5 mL of lipiodol. If the territory of the chemolipiodolized artery did not show stagnant flow, pure lipiodol was then injected. RFA was performed after TACE in 2 months by using a commercially available system (RF 2000; Radio-Therapeutics Mountain View, CA), and a needle electrode with a 15 Ga insulated cannula with 10 hook-shaped expandable electrode tines with a diameter of 3.5 cm at expansion (LeVeen; RadioTherapeutics).
Arm Title
re-resection
Arm Type
Active Comparator
Arm Description
Re-resection was carried out under general anesthesia using a right subcostal incision with a midline extension. Intra-operative ultrasonography was performed routinely to evaluate the tumor burden, liver remnant and the possibility of a negative resection margin. We performed anatomical resection aiming at a resection margin of at least 1 cm. Pringle's maneuver was routinely used with a clamp and unclamp time of 10 minutes and 5 minutes, respectively. Hemostasis of the raw liver surface was done with suturing and application of fibrin glue.
Intervention Type
Procedure
Intervention Name(s)
TACE+RFA
Intervention Description
TACE first, followed by RFA within 2 months
Intervention Type
Procedure
Intervention Name(s)
re-resection
Other Intervention Name(s)
repeat hepatectomy
Intervention Description
repeat hepatectomy for recurrent small HCC
Primary Outcome Measure Information:
Title
overall survival
Time Frame
5 year
Secondary Outcome Measure Information:
Title
disease-free survival
Time Frame
5 year
Other Pre-specified Outcome Measures:
Title
Mortality
Time Frame
30 days
Title
Morbidity
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: age 18 - 75 years; recurrence of HCC 12 months after initial hepatectomy; no other treatment received except for the initial hepatectomy; Single tumor≤5cm in diameter; or 2-3 lesions each ≤ 3.0 cm lesions visible on ultrasound and with an acceptable and safe path between the lesion and the skin as shown on ultrasound; no severe coagulation disorders (prothrombin activity < 40% or a platelet count of < 40,000 / mm3; Eastern Co-operative Oncology Group performance(ECOG) status 0 -1 Exclusion Criteria: the presence of vascular invasion or extrahepatic spread on imaging; a Child-Pugh class C liver cirrhosis or evidence of hepatic decompensation including ascites, severe coagulation disorders (prothrombin activity < 40% or a platelet count of < 40,000 / mm3), esophageal or gastric variceal bleeding or hepatic encephalopathy; an American Society of Anesthesiologists (ASA) score ≥ 3 -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
minshan chen, M.D.
Phone
8620-87343117
Ext
8620-87343117
Email
chminsh@mail.sysu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
yaojun zhang, M.D.
Phone
8620-87343121
Email
zhyaojun@mail.sysu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
minshan chen, M.D.
Organizational Affiliation
Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
minshan chen, M.D.
Phone
8620-87343117
Ext
8620-87343117
Email
chminsh@mail.sysu.edu.cn
First Name & Middle Initial & Last Name & Degree
yaojun zhang, M.D.
Phone
8620-87343121
Email
zhyaojun@mail.sysu.edu.cn
First Name & Middle Initial & Last Name & Degree
minshan chen, M.D.

12. IPD Sharing Statement

Citations:
PubMed Identifier
23269991
Citation
Peng ZW, Zhang YJ, Chen MS, Xu L, Liang HH, Lin XJ, Guo RP, Zhang YQ, Lau WY. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol. 2013 Feb 1;31(4):426-32. doi: 10.1200/JCO.2012.42.9936. Epub 2012 Dec 26.
Results Reference
background
PubMed Identifier
22157201
Citation
Peng ZW, Zhang YJ, Liang HH, Lin XJ, Guo RP, Chen MS. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. 2012 Feb;262(2):689-700. doi: 10.1148/radiol.11110637. Epub 2011 Dec 12.
Results Reference
background
PubMed Identifier
22359112
Citation
Peng ZW, Guo RP, Zhang YJ, Lin XJ, Chen MS, Lau WY. Hepatic resection versus transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus. Cancer. 2012 Oct 1;118(19):4725-36. doi: 10.1002/cncr.26561. Epub 2012 Feb 22.
Results Reference
background

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TACE+RFA Versus Re-resection for Recurrent Small Hepatocellular Carcinoma

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