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

Launched by YONSEI UNIVERSITY · May 14, 2025

Keywords

ClinConnect Summary

The SEVERANCE Trial is a study looking at a medication called everolimus for patients who have had surgery to remove liver cancer (specifically, hepatocellular carcinoma) but are at high risk for the cancer returning. Even after surgery, many patients experience a recurrence of cancer, so researchers want to see if everolimus can help prevent this from happening. This trial will include up to 60 patients who have had successful surgery and have certain risk factors, such as the presence of small blood vessel invasion. Participants will take everolimus orally, twice a day for about 92 weeks, starting a few weeks after surgery.

To be eligible for the trial, patients should have undergone a specific type of surgery without any remaining cancer, and they must meet certain health criteria, such as not having severe kidney issues. Throughout the study, participants will be monitored for any side effects and for how well the treatment is working in preventing cancer recurrence. The main goal is to see if patients remain cancer-free for at least two years after treatment. This study is important because it aims to find effective treatment options for patients at high risk of liver cancer returning after surgery.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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.
• Exclusion Criteria:
• • 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
• • 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.