Clinical trial NCT02867280: Sorafenib Treatment in Patients With Hepatocellular Carcinoma With Microvascular Invasion After Radical Resection
Official title: A Prospective Multicenter Non-randomized Controlled Study of Sorafenib (Nexavar) Treatment in Patients With Hepatocellular Carcinoma With Microvascular Invasion After Radical Resection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Recurrence
Keywords: Sorafenib
Microvascular invasion
adjuvant therapy
hepatocellular carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recurrence free survival
timeFrame: 2 years
Secondary outcomes:
measure: Time To Recurrence
timeFrame: From date of liver resection until the date of first documented relapse, assessed up to 5 years
measure: Recurrence rate
timeFrame: 2 years
measure: Recurrence free survival
timeFrame: 1year, 3years, 5 years
measure: Overall survival
timeFrame: 3 years, 5 years
measure: Incidence of Treatment-related Adverse Events measures using CTCAE v4.0
timeFrame: 2 years
measure: Incidence of dose modification of sorafenib due to adverse events.
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Minshan Chen, PHD
role: PRINCIPAL_INVESTIGATOR
References: