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

• ClinicalTrials.gov Identifier: NCT01681446
• Recruitment Status: Unknown
• First Posted: September 10, 2012
• Last Update Posted: June 1, 2018
• Sponsor: Fudan University
• Information provided by (Responsible Party): Jia Fan, Fudan University

Tracking Information

• First Submitted Date: August 23, 2012
• First Posted Date: September 10, 2012
• Last Update Posted Date: June 1, 2018
• Study Start Date: August 2012
• Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2018)

disease free survival [ Time Frame: 5 years ]

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

• Original Primary Outcome Measures (submitted: September 5, 2012): disease free survival [ Time Frame: 5 years ]

Current Secondary Outcome Measures (submitted: May 30, 2018)

• overall survival [ Time Frame: 5 years ]
  interval between the dates of surgery and patient death
• time to recurrence [ Time Frame: 5 years ]
  interval between the dates of surgery and tumor recurrence
• Number of Participants with Adverse Events [ Time Frame: eighteen months ]
  Number of Participants with Adverse Events（hypohepatia,fever,leukopenia and thrombopenia）will be measured

Original Secondary Outcome Measures (submitted: September 5, 2012)

• overall survival [ Time Frame: 5 years ]
• time to recurrence [ Time Frame: 5 years ]
• Number of Participants with Adverse Events [ Time Frame: eighteen months ]
  Number of Participants with Adverse Events（hypohepatia,fever,leukopenia and thrombopenia）will be measured

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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.
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma

Intervention

Drug: interferon-alpha (IFN-alpha)

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

Other Names:

• Recombinant Human Interferon α1b for Injection
• SINOGEN

Study Arms

• Active Comparator: interferon-alpha (IFN-alpha)
  interferon-alpha is intramuscularly or subcutaneously injected at 30 μg three times a week or 50 μg twice a week for 18 months
  Intervention: Drug: interferon-alpha (IFN-alpha)
• No Intervention: control
  no anti-cancer interventions were assigned

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 30, 2018): 296
• Original Estimated Enrollment (submitted: September 5, 2012): 506
• Estimated Study Completion Date: August 2019
• Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT01681446
• Other Study ID Numbers: LCI IFNa miR-26
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jia Fan, Fudan University
• Original Responsible Party: Same as current
• Current Study Sponsor: Fudan University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jia Fan, MD, PHD; Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
• Principal Investigator: Xin Wei Wang, PhD; National Cancer Institute, NIH, US

• PRS Account: Fudan University
• Verification Date: May 2018