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Adjuvant IFN-α for Patients Underwent Curative Surgery for HCC With a Low miR-26 Expression

Primary Purpose

Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
interferon-alpha (IFN-alpha)
Sponsored by
Fudan 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, interferon-alpha, miR-26

Eligibility Criteria

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

Perioperative Period Inclusion Criteria:

  1. Signed informed consent;
  2. Aged ≥ 18 years and ≤ 75 years old, male or female;
  3. Patients with a low miR-26 expression in tumor (confirmed by RT-PCR) underwent a curative resection of HCC;
  4. The tumor characteristics must meet the following:

    1. tumor diameter is between 3 to 8 centimeters,and the number of tumor is less than 3
    2. no thrombosis is detected in the main branches of the portal vein, hepatic vein and bile duct by preoperative imaging or by intra-operative findings
    3. no extrahepatic and lymph node metastasis

Perioperative Period Exclusion Criteria:

  1. Concomitant malignant primary tumor(s) in other systems is/are present;
  2. The subject receives any previous systemic anti-HCC therapy prior to the resection surgery, such as liver transplantation, intervention, ablation, radiotherapy, chemotherapy, molecular targeted therapy or other anti-HCC therapy;
  3. The subject takes other study/investigational drugs during this study;
  4. The subject has cerebrovascular accident, renal insufficiency, depression, hyperthyreosis, hypothyroidism or other severe uncontrolled diseases;
  5. The subject has a history of study drug or similar drug allergy.

Baseline (Post-Surgery 4 to 6 weeks) Inclusion Criteria:

  1. Baseline (post-resection) blood routine examination shows that the number of leukocyte>2.5*10^9/L and platelet count>40*10^9/L;
  2. Child-Pugh score of class A at baseline.

Baseline (Post-Surgery 4 to 6 weeks) Exclusion Criteria:

  1. Concomitant malignant primary tumor(s) in other systems is/are present;
  2. The subject takes other study/investigational drugs within 4 weeks prior to randomization;
  3. The baseline examination indicates that infection, bleeding, bile leakage, or other postoperative complications are present;
  4. The baseline examination suggests the presence of tumor metastasis;
  5. The subject has cerebrovascular accident, renal insufficiency, depression, hyperthyreosis, hypothyroidism or other severe uncontrolled diseases;
  6. The subject has a history of investigational drug or similar drug allergy;
  7. The subject is pregnant, lactating, or urine pregnancy test result is positive.

Sites / Locations

  • The Mengchao hepatobiliary hospital,Fujian Medical University,and Liver disease research center of Fujian provinceRecruiting
  • Zhongshan Hospital, Xiamen UniversityRecruiting
  • Liver Cancer Institute and Zhongshan Hospital, Fudan UniversityRecruiting
  • ShanghaiBio CoorperationRecruiting
  • Tumor Hospital, Tianjin Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

interferon-alpha (IFN-alpha)

control

Arm Description

interferon-alpha is intramuscularly or subcutaneously injected at 30 μg three times a week or 50 μg twice a week for 18 months

no anti-cancer interventions were assigned

Outcomes

Primary Outcome Measures

disease free survival
interval between the dates of surgery and tumor recurrence or patient death

Secondary Outcome Measures

overall survival
interval between the dates of surgery and patient death
time to recurrence
interval between the dates of surgery and tumor recurrence
Number of Participants with Adverse Events
Number of Participants with Adverse Events(hypohepatia,fever,leukopenia and thrombopenia)will be measured

Full Information

First Posted
August 23, 2012
Last Updated
May 30, 2018
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT01681446
Brief Title
Adjuvant IFN-α for Patients Underwent Curative Surgery for HCC With a Low miR-26 Expression
Official Title
The Effect of Postoperative Interferon-alpha Treatment in Patients Underwent Curative Surgery for Hepatocellular Carcinoma With a Low miR-26 Expression: a Multi-center Randomized Clinical Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2012 (undefined)
Primary Completion Date
August 2019 (Anticipated)
Study Completion Date
August 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to determine whether interferon-alpha is effective in prevention of tumor recurrence for the patients with a low miR-26 expression in tumor after curative resection of hepatocellular carcinoma.
Detailed Description
BACKGROUND: Postoperative interferon-alpha (IFN-alpha) therapy improved survival in patients with hepatocellular carcinoma (HCC). MiR-26 is a predictive marker for the effect of postoperative interferon-alpha treatment in patients with HCC. Our study is to identify the effect of postoperative IFN-alpha treatment in patients with a low miR-26 expression in tumor after resection of HCC. METHODS: A quantitative RT-PCR assays of miR-26 are performed on specimens which are collected from patients who underwent a curative resection of HCC. These patients with low miR-26 expression will return to the hospital 4 to 6 weeks after the resection following the baseline examination to rule out residual tumor. If all requirements are satisfied, these patients will be randomly assigned to the treatment group who received postoperative IFN-alpha therapy or the control group who will not receive any anti-cancer treatment. Disease-free survival, overall survival, time to recurrence and the side effects will be observed. Anticipated RESULTS: IFN-alpha treatment improved the disease-free survival in patients with a low miR-26 expression in tumor after curative resection of HCC, probably by inhibiting tumor recurrence.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
hepatocellular carcinoma, interferon-alpha, miR-26

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
interferon-alpha (IFN-alpha)
Arm Type
Active Comparator
Arm Description
interferon-alpha is intramuscularly or subcutaneously injected at 30 μg three times a week or 50 μg twice a week for 18 months
Arm Title
control
Arm Type
No Intervention
Arm Description
no anti-cancer interventions were assigned
Intervention Type
Drug
Intervention Name(s)
interferon-alpha (IFN-alpha)
Other Intervention Name(s)
Recombinant Human Interferon α1b for Injection, SINOGEN
Intervention Description
interferon-alpha is intramuscular injected 30 μg three times a week or 50 μg twice a week for 18 months
Primary Outcome Measure Information:
Title
disease free survival
Description
interval between the dates of surgery and tumor recurrence or patient death
Time Frame
5 years
Secondary Outcome Measure Information:
Title
overall survival
Description
interval between the dates of surgery and patient death
Time Frame
5 years
Title
time to recurrence
Description
interval between the dates of surgery and tumor recurrence
Time Frame
5 years
Title
Number of Participants with Adverse Events
Description
Number of Participants with Adverse Events(hypohepatia,fever,leukopenia and thrombopenia)will be measured
Time Frame
eighteen months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Perioperative Period Inclusion Criteria: Signed informed consent; Aged ≥ 18 years and ≤ 75 years old, male or female; Patients with a low miR-26 expression in tumor (confirmed by RT-PCR) underwent a curative resection of HCC; The tumor characteristics must meet the following: tumor diameter is between 3 to 8 centimeters,and the number of tumor is less than 3 no thrombosis is detected in the main branches of the portal vein, hepatic vein and bile duct by preoperative imaging or by intra-operative findings no extrahepatic and lymph node metastasis Perioperative Period Exclusion Criteria: Concomitant malignant primary tumor(s) in other systems is/are present; The subject receives any previous systemic anti-HCC therapy prior to the resection surgery, such as liver transplantation, intervention, ablation, radiotherapy, chemotherapy, molecular targeted therapy or other anti-HCC therapy; The subject takes other study/investigational drugs during this study; The subject has cerebrovascular accident, renal insufficiency, depression, hyperthyreosis, hypothyroidism or other severe uncontrolled diseases; The subject has a history of study drug or similar drug allergy. Baseline (Post-Surgery 4 to 6 weeks) Inclusion Criteria: Baseline (post-resection) blood routine examination shows that the number of leukocyte>2.5*10^9/L and platelet count>40*10^9/L; Child-Pugh score of class A at baseline. Baseline (Post-Surgery 4 to 6 weeks) Exclusion Criteria: Concomitant malignant primary tumor(s) in other systems is/are present; The subject takes other study/investigational drugs within 4 weeks prior to randomization; The baseline examination indicates that infection, bleeding, bile leakage, or other postoperative complications are present; The baseline examination suggests the presence of tumor metastasis; The subject has cerebrovascular accident, renal insufficiency, depression, hyperthyreosis, hypothyroidism or other severe uncontrolled diseases; The subject has a history of investigational drug or similar drug allergy; The subject is pregnant, lactating, or urine pregnancy test result is positive.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mei-ling Li
Phone
64041990
Ext
2936
Email
livercongress@zs-hospital.sh.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jia Fan, MD, PHD
Organizational Affiliation
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Xin Wei Wang, PhD
Organizational Affiliation
National Cancer Institute, NIH, US
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Mengchao hepatobiliary hospital,Fujian Medical University,and Liver disease research center of Fujian province
City
Fuzhou
State/Province
Fujian
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jingfeng Liu
Email
drjingfeng@yahoo.com.cn
First Name & Middle Initial & Last Name & Degree
Jingfeng Liu
Facility Name
Zhongshan Hospital, Xiamen University
City
Xiamen
State/Province
Fujian
ZIP/Postal Code
361004
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ping-Guo Liu, MD
First Name & Middle Initial & Last Name & Degree
Ping-Guo Liu, MD
Facility Name
Liver Cancer Institute and Zhongshan Hospital, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mei-ling Li
Phone
64041990
Ext
2936
Email
livercongress@zs-hospital.sh.cn
First Name & Middle Initial & Last Name & Degree
Jia Fan, MD
First Name & Middle Initial & Last Name & Degree
Hui-Chuan Sun, MD
Facility Name
ShanghaiBio Coorperation
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jason Gang Jin, PhD
Phone
13818588366
Email
jasongjin@gmail.com
First Name & Middle Initial & Last Name & Degree
Jason Gang Jin, MD, PhD
Facility Name
Tumor Hospital, Tianjin Medical University
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ti Zhang, MD
Email
zhangti2001@yahoo.com.cn
First Name & Middle Initial & Last Name & Degree
Qiang Li, MD
First Name & Middle Initial & Last Name & Degree
Ti Zhang, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
19812400
Citation
Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009 Oct 8;361(15):1437-47. doi: 10.1056/NEJMoa0901282.
Results Reference
background
PubMed Identifier
16557381
Citation
Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol. 2006 Jul;132(7):458-65. doi: 10.1007/s00432-006-0091-y. Epub 2006 Mar 24.
Results Reference
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PubMed Identifier
17522506
Citation
Lo CM, Liu CL, Chan SC, Lam CM, Poon RT, Ng IO, Fan ST, Wong J. A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann Surg. 2007 Jun;245(6):831-42. doi: 10.1097/01.sla.0000245829.00977.45.
Results Reference
background
PubMed Identifier
17522507
Citation
Clavien PA. Interferon: the magic bullet to prevent hepatocellular carcinoma recurrence after resection? Ann Surg. 2007 Jun;245(6):843-5. doi: 10.1097/SLA.0b013e31805d0788. No abstract available.
Results Reference
background
PubMed Identifier
16948122
Citation
Qian YB, Zhang JB, Wu WZ, Fang HB, Jia WD, Zhuang PY, Zhang BH, Pan Q, Xu Y, Wang L, Tang ZY, Sun HC. P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma. Cancer. 2006 Oct 1;107(7):1562-9. doi: 10.1002/cncr.22206.
Results Reference
background
PubMed Identifier
10869287
Citation
Wang L, Tang ZY, Qin LX, Wu XF, Sun HC, Xue Q, Ye SL. High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology. 2000 Jul;32(1):43-8. doi: 10.1053/jhep.2000.8525.
Results Reference
background
PubMed Identifier
12850669
Citation
Wang L, Wu WZ, Sun HC, Wu XF, Qin LX, Liu YK, Liu KD, Tang ZY. Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J Gastrointest Surg. 2003 Jul-Aug;7(5):587-94. doi: 10.1016/s1091-255x(03)00072-6.
Results Reference
background

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Adjuvant IFN-α for Patients Underwent Curative Surgery for HCC With a Low miR-26 Expression

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