CarcinomPhase 2NCT06972758
Adjuvant Everolimus in High-Risk Hepatocellular Carcinoma After Curative Resection (SEVERANCE Trial)
A Phase 2 study testing Certirobell® in people with Carcinom and Hepatocellular, run by Yonsei University.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Carcinom, Hepatocellular
- What is being tested?
- Certirobell®
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2025to 30 Jul 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- Patients diagnosed with combined hepatocellular-cholangiocarcinoma (HCC-CCC)
- Presence of clinically significant ascites
- History of hepatic encephalopathy
- History of variceal bleeding within 6 months prior to hepatic resection
- 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
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- History of malignancies other than HCC within the past 5 years
- Patients with hereditary metabolic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
- Patients currently taking medication for psychiatric disorders
- 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
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase II Study of EVEerolimus as Adjuvant Therapy After Surgical Resection for Hepatocellular cArcinoma at High Risk of RecurreNCE [SEVERANCE Trial]
"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.
Read more
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
- Being tested
- Certirobell®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Certirobell®Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treamtent group | Experimental | Patients recieving study drug Receives: Drug: Certirobell® |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year recurrence-free survival rate
The 2-year recurrence-free survival (RFS) is defined as the proportion of patients who remain alive without intrahepatic or extrahepatic recurrence at 2 years from the time of hepatic resection.
Measured: 2-year from hepatic resection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2025
- Study start1 Jul 2025 (estimated)
- Primary completion1 Jul 2030 (estimated)
- Study completion30 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CarcinomStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06972758
- Sponsor's protocol ID
- 4-2025-0275
- Status last verified
- May 2025
- First submitted
- 7 May 2025
- Last updated
- 15 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of EVEerolimus as Adjuvant Therapy After Surgical Resection for Hepatocellular cArcinoma at High Risk of RecurreNCE [SEVERANCE Trial]
- ClinicalTrials.gov ID
- NCT06972758
- Acronym / sponsor ID
- 4-2025-0275
- Conditions
- Carcinom, Hepatocellular
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 1 Jul 2025 (estimated)
- Primary completion
- 1 Jul 2030 (estimated)
- Study completion
- 30 Jul 2030 (estimated)
- First posted
- 15 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
"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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treamtent group | Experimental | Drug: Certirobell®Patients recieving study drug |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (21 listed)
- Patients diagnosed with combined hepatocellular-cholangiocarcinoma (HCC-CCC)
- Presence of clinically significant ascites
- History of hepatic encephalopathy
- History of variceal bleeding within 6 months prior to hepatic resection
- Autoimmune diseases or immunodeficiency disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Treamtent group |
Primary outcome
2-year recurrence-free survival rate
Time frame: 2-year from hepatic resection
The 2-year recurrence-free survival (RFS) is defined as the proportion of patients who remain alive without intrahepatic or extrahepatic recurrence at 2 years from the time of hepatic resection.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
- Individual participant dataSharing planned: No
Related trials for Carcinom
Not yet recruitingObservational study
Conversion Therapy Using TACE/HAIC With Anti-Angiogenic and Immunotherapy for Initially Unresectable Hepatocellular Carcinoma Achieving Complete Response or Resectability, Followed by Surgery or Continued Systemic Treatment: A Prospective Cohort Study
Unresectable Hepatocellular Carcinom
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Certirobell® in people with Carcinom and Hepatocellular, run by Yonsei University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dong Jin Joo, MD,PhD ((+82 2) 2228 - 2131, djjoo@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year recurrence-free survival rate (time frame: 2-year from hepatic resection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025; AzTrials last refreshed its copy on 6 Nov 2026.