NCT06972758Not yet recruitingPhase 2
Adjuvant Everolimus in High-Risk Hepatocellular Carcinoma After Curative Resection (SEVERANCE Trial)
A Phase II Study of EVEerolimus as Adjuvant Therapy After Surgical Resection for Hepatocellular cArcinoma at High Risk of RecurreNCE [SEVERANCE Trial]
Source: ClinicalTrials.gov · Last updated 15 May 2025 · Not updated for over 12 months - ask the site whether it is still open
Brief summary (registry, in English)
"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.
- Status (registry)
- Not yet recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 60 (estimated)
- First submitted
- 7 May 2025
- Start date
- 1 Jul 2025
- Primary completion date
- 1 Jul 2030
- Lead sponsor
- Yonsei University
- Diseases
- Liver and biliary tract cancer
- NCT number
- NCT06972758
What you commit to
- Study type: Interventional · Phase 2
- Planned participants: 60
- From 1 Jul 2025 to the primary completion date, 1 Jul 2030
- No sites listed in no country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- History of variceal bleeding within 6 months prior to hepatic resection
- Patients currently taking medication for psychiatric disorders
- Patients who received systemic therapy prior to hepatic resection
- Prior treatment with anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapies
Other illness
- History of hepatic encephalopathy
- Autoimmune diseases or immunodeficiency disorders
- Serious cardiovascular diseases, including acute myocardial infarction, acute coronary syndrome, stroke, or heart failure of New York Heart Association (NYHA) Class II or higher
- History of malignancies other than HCC within the past 5 years
- History of severe acute (within the past 4 weeks) or chronic hypersensitivity reactions requiring treatment to everolimus or drugs with a similar chemical structure
- Any condition deemed by the investigator to render the patient unsuitable for participation in the clinical trial
- Highly effective contraception is defined as methods with a failure rate of less than 1% per year, including bilateral tubal occlusion, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Methods such as calendar-based methods, ovulation prediction, symptothermal methods, and post-ovulation methods are not considered adequate contraception.
Lab values
- Patients with hereditary metabolic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- Absolute neutrophil count (ANC) \< 1500/μL or platelet count \< 75,000/μL
- AST, ALT, or total bilirubin levels \> 3 times the upper limit of normal (ULN)
- Alkaline phosphatase level \> 2.5 times the ULN
- Proteinuria defined as a urine protein-to-creatinine ratio \> 1.0 g/gCr or ≥ 2+ on urine dipstick
- Renal impairment with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m² (based on MDRD formula)
- Total cholesterol \> 350 mg/dL or triglycerides \> 500 mg/dL
Other
- Patients diagnosed with combined hepatocellular-cholangiocarcinoma (HCC-CCC)
- Presence of clinically significant ascites
- Pregnant or breastfeeding women, women who are possibly pregnant, or women of childbearing potential who are unable to use highly effective contraception† during the study period and for 8 weeks after the last dose
Who the study is looking for
- Alkaline phosphatase level \> 2.5 times the ULN
- Proteinuria defined as a urine protein-to-creatinine ratio \> 1.0 g/gCr or ≥ 2+ on urine dipstick
- Patients who received systemic therapy prior to hepatic resection
- Prior treatment with anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapies
- Renal impairment with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m² (based on MDRD formula)
- Total cholesterol \> 350 mg/dL or triglycerides \> 500 mg/dL
- History of severe acute (within the past 4 weeks) or chronic hypersensitivity reactions requiring treatment to everolimus or drugs with a similar chemical structure
- Pregnant or breastfeeding women, women who are possibly pregnant, or women of childbearing potential who are unable to use highly effective contraception† during the study period and for 8 weeks after the last dose
- Any condition deemed by the investigator to render the patient unsuitable for participation in the clinical trial
- Highly effective contraception is defined as methods with a failure rate of less than 1% per year, including bilateral tubal occlusion, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Methods such as calendar-based methods, ovulation prediction, symptothermal methods, and post-ovulation methods are not considered adequate contraception.
Age in the registry: 20 years to 75 years · Sex: All · Does not accept healthy volunteers
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