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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Terminated

CT.gov ID

NCT02867280

Collaborator

(none)

154

Enrollment

Location

Arms

Actual Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Recurrence	Drug: Sorafenib	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

154 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2016

Actual Primary Completion Date :

Aug 31, 2019

Actual Study Completion Date :

Jan 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib Sorafenib (Nexavar) 200mg tablet, 2 tablets oral daily for 2 years, starting within 4weeks after hepatectomy. Regular treatment combined.	Drug: Sorafenib red round tablet Other Names: Nexavar
No Intervention: Control No use of Sorafenib (Nexavar). Regular treatment.

Arm

Intervention/Treatment

Experimental: Sorafenib

Sorafenib (Nexavar) 200mg tablet, 2 tablets oral daily for 2 years, starting within 4weeks after hepatectomy. Regular treatment combined.

Drug: Sorafenib

red round tablet

Other Names:

Nexavar

No Intervention: Control

No use of Sorafenib (Nexavar). Regular treatment.

Outcome Measures

Primary Outcome Measures

Recurrence free survival [2 years]
To determine the recurrence free survival rate at 2 years after hepatectomy

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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