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Adjuvant Everolimus in High-Risk Hepatocellular Carcinoma After Curative Resection (SEVERANCE Trial)

NCT06972758 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 60

Last updated 2025-05-15

No results posted yet for this study

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.

Conditions

  • Carcinom
  • Hepatocellular

Interventions

DRUG

Certirobell®

Patients enrolled in the study will initiate oral administration of Certirobell® between 4 to 6 weeks after hepatic resection. The medication will be taken for a duration of 92 weeks, twice daily at approximately 12-hour intervals. The initial dosage is 1.0 mg per dose (twice daily). For patients with a Child-Pugh score of 6, the starting dose will be reduced to 0.75 mg per dose (twice daily). At each visit, the blood concentration of Certirovel will be measured, and the investigator will adjust the dosage as needed to maintain levels within the target range of 3-8 ng/mL. If HCC recurrence is confirmed during treatment, the administration of the drug will be discontinued.

Sponsors & Collaborators

  • Yonsei University

    lead OTHER

Study Design

Allocation
NA
Purpose
PREVENTION
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
20 Years
Max Age
75 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-07-01
Primary Completion
2030-07-01
Completion
2030-07-30

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06972758 on ClinicalTrials.gov