Ignite Creation Date:
2025-12-25 @ 12:10 AM
Ignite Modification Date:
2025-12-25 @ 10:10 PM
Study NCT ID:
NCT06972758
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-05-15
First Post:
2025-05-07
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Adjuvant Everolimus in High-Risk Hepatocellular Carcinoma After Curative Resection (SEVERANCE Trial)
Sponsor:
Yonsei University
Organization:
Study Overview
Official Title:
A Phase II Study of EVEerolimus as Adjuvant Therapy After Surgical Resection for Hepatocellular cArcinoma at High Risk of RecurreNCE [SEVERANCE Trial]
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
"Hepatic resection is the primary curative treatment for patients with a single, liver-confined hepatocellular carcinoma (HCC) without cirrhosis and is also considered in patients with cirrhosis if residual liver function is sufficient. Despite curative resection, HCC has a high recurrence rate, with 5-year recurrence reported in approximately 50-70% of patients. Notably, in cases with microvascular invasion, the 2-year recurrence rate reaches 55-75%. As early recurrence strongly impacts overall survival, there is a critical need for effective adjuvant therapies; however, no adjuvant treatment has yet been established or officially recommended.
Everolimus is an mTOR inhibitor that has both immunosuppressive and antitumor effects. Approximately half of HCC cases exhibit activation of the mTOR pathway. In liver transplant recipients, everolimus is used as an immunosuppressive agent and has been associated with reduced recurrence and improved survival, particularly in patients with elevated tumor markers prior to transplantation. Preclinical studies at our institution have shown that mTOR inhibitors may be more effective in preventing tumor development than in treating established tumors, suggesting a potential benefit for everolimus in an adjuvant setting.
To date, no clinical trials have assessed the efficacy of everolimus as adjuvant therapy after curative hepatic resection, especially in high-risk HCC characterized by microvascular invasion or satellite nodules. This study aims to evaluate the efficacy and safety of everolimus (Certirobell®) as adjuvant therapy in high-risk HCC patients following curative resection.
This is a single-center, single-arm Phase II trial conducted at Severance Hospital. A total of 60 patients with pathologically confirmed HCC who underwent R0 resection and exhibit high-risk features for recurrence will be enrolled. Everolimus will be administered orally, twice daily for 92 weeks, starting 4 to 6 weeks postoperatively. Initial dosing will be 1.0 mg twice daily, adjusted to 0.75 mg for patients with a Child-Pugh score of 6. Dosage adjustments will be made based on everolimus trough levels, targeting 3-8 ng/mL. Treatment will be discontinued upon confirmation of HCC recurrence.
The primary endpoint is 2-year recurrence-free survival (RFS). Secondary endpoints include 1-year RFS, 2-year recurrence rate, overall survival (OS), time to recurrence, and safety outcomes.
An interim analysis will be conducted after the first 30 patients have been enrolled and followed for 2 years. Based on the interim assessment of efficacy or futility, the study will either be terminated early or proceed with enrollment of an additional 30 patients.
Everolimus is an mTOR inhibitor that has both immunosuppressive and antitumor effects. Approximately half of HCC cases exhibit activation of the mTOR pathway. In liver transplant recipients, everolimus is used as an immunosuppressive agent and has been associated with reduced recurrence and improved survival, particularly in patients with elevated tumor markers prior to transplantation. Preclinical studies at our institution have shown that mTOR inhibitors may be more effective in preventing tumor development than in treating established tumors, suggesting a potential benefit for everolimus in an adjuvant setting.
To date, no clinical trials have assessed the efficacy of everolimus as adjuvant therapy after curative hepatic resection, especially in high-risk HCC characterized by microvascular invasion or satellite nodules. This study aims to evaluate the efficacy and safety of everolimus (Certirobell®) as adjuvant therapy in high-risk HCC patients following curative resection.
This is a single-center, single-arm Phase II trial conducted at Severance Hospital. A total of 60 patients with pathologically confirmed HCC who underwent R0 resection and exhibit high-risk features for recurrence will be enrolled. Everolimus will be administered orally, twice daily for 92 weeks, starting 4 to 6 weeks postoperatively. Initial dosing will be 1.0 mg twice daily, adjusted to 0.75 mg for patients with a Child-Pugh score of 6. Dosage adjustments will be made based on everolimus trough levels, targeting 3-8 ng/mL. Treatment will be discontinued upon confirmation of HCC recurrence.
The primary endpoint is 2-year recurrence-free survival (RFS). Secondary endpoints include 1-year RFS, 2-year recurrence rate, overall survival (OS), time to recurrence, and safety outcomes.
An interim analysis will be conducted after the first 30 patients have been enrolled and followed for 2 years. Based on the interim assessment of efficacy or futility, the study will either be terminated early or proceed with enrollment of an additional 30 patients.
Detailed Description:
None
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: