Clinical trial NCT01681446: 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
interferon-alpha
miR-26
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2012-09-10
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: disease free survival
timeFrame: 5 years
Secondary outcomes:
measure: overall survival
timeFrame: 5 years
measure: time to recurrence
timeFrame: 5 years
measure: Number of Participants with Adverse Events
timeFrame: eighteen months
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: The Mengchao hepatobiliary hospital，Fujian Medical University，and Liver disease research center of Fujian province
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital, Xiamen University
state: Fujian
city: Shanghai
country: China
facility: Liver Cancer Institute and Zhongshan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: ShanghaiBio Coorperation
state: Shanghai
city: Tianjin
country: China
facility: Tumor Hospital, Tianjin Medical University
state: Tianjin
Study officials:
affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
name: Jia Fan, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, NIH, US
name: Xin Wei Wang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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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.
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.
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.
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.