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

Phase 3

Terminated

• Conditions: Hepatocellular Carcinoma; Recurrence
• Interventions: Drug: Sorafenib

• Registration Number: NCT02867280
• Lead Sponsor: Sun Yat-sen University

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.

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 Timeline

• Study Start: 2016-06-01
• Study First Submitted: 2016-07-10
• Study First Submitted QC: 2016-08-11
• Study First Posted: 2016-08-15
• Primary Completion: 2019-08-31
• Study Completion: 2020-01-31
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-09
• Last Update Posted: 2020-02-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 154

Inclusion Criteria

1. Age 18-75 years
2. Hepatocellular carcinoma confirmed by pathology
3. No macroscopic tumor thrombus vascular invasion and distant metastasis
4. R0 resection（clean resection margin both macroscopically and microscopically）
5. MVI confirmed by pathology
6. ECOG 0-1
7. Child-Pugh stage A
8. WBC > 3×10E9/L；HB > 90 G/L；PLT > 50×10E9/L
9. 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

1. Tumor rupture or invading to adjacent organs
2. Patients who underwent liver transplantation
3. Past history of or simultaneously receiving other anti-cancer therapy (such as TACE, chemotherapy, radiotherapy and others）and immune cell infusion therapy
4. Uncontrolled cardiovascular and cerebrovascular diseases
5. History of gastrointestinal bleeding within 6 months
6. Active infection other than HBV, HCV
7. Postoperative complications, not suitable to take Sorafenib (such as long term use of drainage due to bile leakage, poor wound healing and others)
8. Confirmed liver cancer recurrence or metastasis within 4 weeks after hepatectomy
9. Poor compliance, cannot adhere to regular follow up
10. Diagnosed with other original malignant tumors other than HCC

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Recurrence free survival	2 years	To determine the recurrence free survival rate at 2 years after hepatectomy

Secondary Outcome Measures

Name	Time	Method
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
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.
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

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China