Sorafenib Treatment in Patients With Hepatocellular Carcinoma With Microvascular Invasion After Radical Resection

Study Overview
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Brief Summary
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This prospective multicenter non-randomized controlled study evaluates the efficacy and safety of treatment with Sorafenib (Nevaxar) in patients with hepatocellular carcinoma with microvascular invasion after radical resection compared to conventional therapies.

Detailed Description
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The study is a multicenter, non-randomized, open-label, blank controlled study which initiated by Investigators. The study population include patients without macroscopic vascular invasion and distant metastasis, undergoing R0 resection, postoperative pathology confirming hepatocellular carcinoma with microvascular invasion (MVI) (BCLC A or B stage; T2 or part T3aN0M0). The primary end point of this study is recurrence free survival（RFS）at the 2nd postoperative years, and the secondary end points include postoperative median time to recurrence (TTR), 1-year, 3-years, 5-years postoperative recurrence free survival (RFS), 3-years, 5-years postoperative overall survival, and safety and tolerance of sorafenib as an adjuvant therapy for HCC. Patients in the treatment group will start Sorafenib within 4 weeks after hepatectomy at doze of 400mg per day, and last continuously for 2 years, or until disease progression. Patients in the control group will take regular treatment with no use of Sorafenib. Both groups are forbid receiving postoperative anti-cancer therapy such as adjuvant radiotherapy, chemotherapy and TACE. Patients of both groups should receive antiviral therapy according to guidelines. Chinese traditional medicine and nutritional support can be used without limitation, and the information of concomitant drug need to be recorded for further analysis. Treatment for relieve drug related AEs can be used as needed. Patients of both groups will be treated with best clinical practice as routine after confirmed recurrence/metastasis, and the information of further treatment need to be recorded and follow-up till death.

Official Title
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A Prospective Multicenter Non-randomized Controlled Study of Sorafenib (Nexavar) Treatment in Patients With Hepatocellular Carcinoma With Microvascular Invasion After Radical Resection

Conditions
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Hepatocellular Carcinoma, Recurrence

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Hepatocellular carcinoma confirmed by pathology No macroscopic tumor thrombus vascular invasion and distant metastasis R0 resection（clean resection margin both macroscopically and microscopically） MVI confirmed by pathology ECOG 0-1 Child-Pugh stage A WBC > 3×10E9/L；HB > 90 G/L；PLT > 50×10E9/L ALT，AST not exceeding 5 times of the upper limit of normal value；CRE，TBIL not exceeding 1.5 times of the upper limit of normal value Exclusion Criteria: Tumor rupture or invading to adjacent organs Patients who underwent liver transplantation Past history of or simultaneously receiving other anti-cancer therapy (such as TACE, chemotherapy, radiotherapy and others）and immune cell infusion therapy Uncontrolled cardiovascular and cerebrovascular diseases History of gastrointestinal bleeding within 6 months Active infection other than HBV, HCV Postoperative complications, not suitable to take Sorafenib (such as long term use of drainage due to bile leakage, poor wound healing and others) Confirmed liver cancer recurrence or metastasis within 4 weeks after hepatectomy Poor compliance, cannot adhere to regular follow up Diagnosed with other original malignant tumors other than HCC

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib<br>Sorafenib (Nexavar) 200mg tablet, 2 tablets oral daily for 2 years, starting within 4weeks after hepatectomy. Regular treatment combined. | Drug: Sorafenib<br>* red round tablet<br>* Other names: Nexavar;|
| No Intervention: Control<br>No use of Sorafenib (Nexavar). Regular treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence free survival | To determine the recurrence free survival rate at 2 years after hepatectomy | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time To Recurrence | To determine the median postoperative time to recurrence | From date of liver resection until the date of first documented relapse, assessed up to 5 years | 
| Recurrence rate | To determine the recurrence rate within 2 years after hepatectomy | 2 years | 
| Recurrence free survival | To determine the recurrence free survival at postoperative 1-year, 3-year, and 5-year | 1year, 3years, 5 years | 
| Overall survival | To determine the overall survival at postoperative 3-year and 5-year | 3 years, 5 years | 
| Incidence of Treatment-related Adverse Events measures using CTCAE v4.0 | measures using CTCAE v4.0 | 2 years | 
| Incidence of dose modification of sorafenib due to adverse events. | The actual total dose of sorafenib for every patients will be collected as well. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sorafenib, Microvascular invasion, adjuvant therapy, hepatocellular carcinoma