Carcinoma, HepatocellularPhase 2RELEVANT-HCCNCT07514429
Regorafenib After Failure of Lenvatinib in Patients With Unresectable HCC: The RELEVANT-HCC Trial
A Phase 2 study testing Regorafenib (BAY 73-4506) in people with Carcinoma, Hepatocellular and Lenvatinib, run by Ju Hyun Shim at 1 site in South Korea.
Trial summary
The purpose of this clinical trial is to evaluate the efficacy and safety of regorafenib as a subsequent therapy for patients with hepatocellular carcinoma (HCC) who have failed prior lenvatinib treatment. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular, Lenvatinib, Treatment Failure
- What is being tested?
- Regorafenib (BAY 73-4506)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSouth Korea
- Study dates
- 15 Mar 2026to 30 Jun 2028
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form.
- Age ≥ 19 years at the time of signing the informed consent form.
- Diagnosis of hepatocellular carcinoma (HCC) confirmed histologically or clinically according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.
- Patients with unresectable HCC who have experienced disease progression or treatment discontinuation due to toxicity during prior treatment with lenvatinib.
- Presence of at least one measurable target lesion according to RECIST v1.1.
- Child-Pugh classification A or B7 (score 7).
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Adequate hematologic and end-organ function defined by the following laboratory test results obtained within 14 days prior to testing (or enrollment):
- Hemoglobin ≥ 8.5 g/dL
- Absolute neutrophil count (ANC) ≥ 1,200/mm³
- Platelet count ≥ 60,000/μL
- Total bilirubin < 3.5 mg/dL
- Serum albumin ≥ 2.5 g/dL
- AST and ALT ≤ 7 × upper limit of normal (ULN)
- Prothrombin time (INR ≤ 1.8 × ULN)
- Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault equation)
- Virological status of hepatitis confirmed and recorded through HBV and HCV screening.
- Participants with HBV or HCV infection must be receiving antiviral therapy according to institutional guidelines.
- Women of childbearing potential must agree to maintain abstinence or use effective contraception (with an annual failure rate of < 1%) from the time of signing the informed consent until at least 6 months after the last dose of the study drug. Male participants must agree to maintain abstinence or use effective contraception (with an annual failure rate of < 1%) and refrain from sperm donation from the time of signing the informed consent until at least 6 months after the last dose of the study drug.
Who cannot join
- Albumin-bilirubin (ALBI) grade 3.
- Fibrolamellar carcinoma or sarcomatoid carcinoma.
- Prior treatment with regorafenib.
- History of allogeneic stem cell transplantation or solid organ transplantation.
- Active brain metastases or leptomeningeal metastases.
- History of malignancy other than hepatocellular carcinoma (HCC) within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year survival rate > 90%).
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- Severe cardiovascular disease within 3 months prior to the start of study therapy (e.g., New York Heart Association [NYHA] Class II or higher heart disease, myocardial infarction, or cerebrovascular accident); uncontrolled serious medical comorbidities, including unstable arrhythmia or unstable angina; or other significant medical conditions or abnormal findings that, in the opinion of the investigator, may increase the risk associated with study participation.
- Female participants who are pregnant or breastfeeding, or male or female participants of reproductive potential who are unwilling to use effective contraception from screening until 6 months after the last dose of the study drug.
- Participants deemed by the investigator to be unlikely to comply with study procedures, restrictions, and requirements.
- Patients who have received locoregional therapy (e.g., radiofrequency ablation [RFA], microwave ablation [MWA], transarterial chemoembolization [TACE], transarterial radioembolization [TARE], transarterial embolization [TAE], radiation therapy, etc.) after discontinuation of lenvatinib treatment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site
Asan Medical Center
Seoul, 05505
Ju Hyun Shim, MD PhD, 82-2-03103190, s5854@amc.seoul.kr
Sung Won Chung, MD, 82-2-3010-1105, schungaa@gmail.com
About this study
Official title: Regorafenib After Failure of Lenvatinib in Patients With Unresectable HCC: A Phase 2 RELEVANT-HCC Trial
The purpose of this clinical trial is to evaluate the efficacy and safety of regorafenib as a subsequent therapy for patients with hepatocellular carcinoma (HCC) who have failed prior lenvatinib treatment. This investigational study aims to assess the therapeutic benefits and safety profile of regorafenib in patients whose disease has progressed following the use of lenvatinib, a targeted therapy for hepatocellular carcinoma
Read the detailed description
Lenvatinib is currently recognized as a standard first-line treatment for advanced hepatocellular carcinoma (HCC), having demonstrated non-inferiority to sorafenib in a phase 3 randomized clinical trial. It is also utilized as a second-line option following the failure of immunotherapy-based regimens. However, unlike sorafenib, there is a lack of prospective data regarding subsequent therapies following lenvatinib failure, which poses significant challenges in clinical decision-making.
Regorafenib has demonstrated clinical efficacy and significant survival benefits compared to placebo in the RESORCE trial as a second-line treatment after sorafenib for Child-Pugh class A patients. Nevertheless, evidence supporting its use specifically in patients who have failed lenvatinib remains insufficient.
This multicenter, single-arm, phase 2 study is designed to evaluate the efficacy and safety of regorafenib as a subsequent therapy for patients with unresectable HCC who have experienced disease progression or unacceptable toxicity during prior treatment with lenvatinib.
Enrolled participants will receive regorafenib orally. The starting dose for Cycle 1 will be determined by the baseline Child-Pugh classification (160 mg once daily for Child-Pugh A; 120 mg once daily for Child-Pugh B). From Cycle 2 onwards, patients will maintain a standard regimen of 3 weeks on and 1 week off at the maximum tolerated dose. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. The study will assess key efficacy endpoints including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR), alongside comprehensive safety evaluations.
- Conditions
- Carcinoma, Hepatocellular, Lenvatinib, Treatment Failure
- Being tested
- Regorafenib (BAY 73-4506)
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib (BAY 73-4506)Drug
"Participants with unresectable hepatocellular carcinoma who have failed prior lenvatinib treatment will receive oral regorafenib. The starting dose for Cycle 1 is 160 mg once daily for patients with Child-Pugh class A, and 120 mg once daily for patients with Child-Pugh class B. From Cycle 2 onwards, regorafenib will be administered at the maximum tolerated dose on a schedule of 3 weeks on and 1 week off (28-day cycle). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | "Participants with unresectable hepatocellular carcinoma who have failed prior lenvatinib treatment will receive oral regorafenib. The starting dose for Cycle 1 is 160 mg once daily for patients with Child-Pugh class A, and 120 mg once daily for patients with Child-Pugh class B. From Cycle 2 onwards, regorafenib will be administered at the maximum tolerated dose on a schedule of 3 weeks on and 1 week off (28-day cycle). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or study termination Receives: Drug: Regorafenib (BAY 73-4506) |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival
Tumor assessments every 12 weeks (±7 days) after treatment discontinuation without documented progression until progression, death, or end of follow-up, whichever occurs first.
Measured: From date of first dose until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 36 months.
Secondary outcomes (5)
Overall survival
Survival follow-up assessments are conducted every 12 weeks (±7 days) after treatment discontinuation due to disease progression or withdrawal until death or end of follow-up.
Measured: From date of first dose until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 36 months.
time to progression
Baseline and scheduled tumor imaging assessments every 12 weeks (±7 days) thereafter (date of documented PD per RECIST v1.1).
Measured: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
objective response rate
Assessment of Best Overall Response (CR/PR) at scheduled tumor imaging time points (every 12 weeks ±7 days) from treatment initiation until first PD or start of subsequent systemic anticancer therapy.
Measured: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
disease control rate
Assessment of Best Overall Response (CR/PR/SD) at scheduled tumor imaging time points (every 12 weeks ±7 days) from treatment initiation until first PD or start of subsequent systemic anticancer therapy.
Measured: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse events will be graded according to the NCI CTCAE version 5.0.
Measured: From first dose of study drug until 30 days after last dose, assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2026
- Study start15 Mar 2026 (estimated)
- Primary completion31 May 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-arm study. All enrolled participants will be assigned to a single group and receive the investigational treatment, regorafenib, according to their baseline Child-Pugh classification. There is no control group or randomization in this study
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ju Hyun Shim
- Sponsor type
- University, hospital or other
- Collaborators
- Boryung Pharmaceutical Co., Ltd, Samsung Medical Center, Seoul National University Hospital, Seoul National University Bundang Hospital, National Cancer Center, Korea, Hanyang University Guri Hospital
- Responsible party
- Sponsor-investigator, Ju Hyun Shim, Asan Medical Center
- Investigators
- Ju Hyun Shim, MD PhD, Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07514429
- Sponsor's protocol ID
- 2026-0014
- Acronym
- RELEVANT-HCC
- Status last verified
- Mar 2026
- First submitted
- 24 Mar 2026
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regorafenib After Failure of Lenvatinib in Patients With Unresectable HCC: A Phase 2 RELEVANT-HCC Trial
- ClinicalTrials.gov ID
- NCT07514429
- Acronym / sponsor ID
- RELEVANT-HCC / 2026-0014
- Conditions
- Carcinoma, Hepatocellular, Lenvatinib, Treatment Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Ju Hyun ShimUniversity, hospital or other
- Collaborators
- Boryung Pharmaceutical Co., Ltd, Samsung Medical Center, Seoul National University Hospital, Seoul National University Bundang Hospital, National Cancer Center, Korea, Hanyang University Guri Hospital
- Study start
- 15 Mar 2026 (estimated)
- Primary completion
- 31 May 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 7 Apr 2026 (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.
The purpose of this clinical trial is to evaluate the efficacy and safety of regorafenib as a subsequent therapy for patients with hepatocellular carcinoma (HCC) who have failed prior lenvatinib treatment. This investigational study aims to assess the therapeutic benefits and safety profile of regorafenib in patients whose disease has progressed following the use of lenvatinib, a targeted therapy for hepatocellular carcinoma
Detailed description
Lenvatinib is currently recognized as a standard first-line treatment for advanced hepatocellular carcinoma (HCC), having demonstrated non-inferiority to sorafenib in a phase 3 randomized clinical trial. It is also utilized as a second-line option following the failure of immunotherapy-based regimens. However, unlike sorafenib, there is a lack of prospective data regarding subsequent therapies following lenvatinib failure, which poses significant challenges in clinical decision-making.
Regorafenib has demonstrated clinical efficacy and significant survival benefits compared to placebo in the RESORCE trial as a second-line treatment after sorafenib for Child-Pugh class A patients. Nevertheless, evidence supporting its use specifically in patients who have failed lenvatinib remains insufficient.
This multicenter, single-arm, phase 2 study is designed to evaluate the efficacy and safety of regorafenib as a subsequent therapy for patients with unresectable HCC who have experienced disease progression or unacceptable toxicity during prior treatment with lenvatinib.
Enrolled participants will receive regorafenib orally. The starting dose for Cycle 1 will be determined by the baseline Child-Pugh classification (160 mg once daily for Child-Pugh A; 120 mg once daily for Child-Pugh B). From Cycle 2 onwards, patients will maintain a standard regimen of 3 weeks on and 1 week off at the maximum tolerated dose. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. The study will assess key efficacy endpoints including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR), alongside comprehensive safety evaluations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-arm study. All enrolled participants will be assigned to a single group and receive the investigational treatment, regorafenib, according to their baseline Child-Pugh classification. There is no control group or randomization in this study
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: Regorafenib (BAY 73-4506)"Participants with unresectable hepatocellular carcinoma who have failed prior lenvatinib treatment will receive oral regorafenib. The starting dose for Cycle 1 is 160 mg once daily for patients with Child-Pugh class A, and 120 mg once daily for patients with Child-Pugh class B. From Cycle 2 onwards, regorafenib will be administered at the maximum tolerated dose on a schedule of 3 weeks on and 1 week off (28-day cycle). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or study termination |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed informed consent form.
- Age ≥ 19 years at the time of signing the informed consent form.
- Diagnosis of hepatocellular carcinoma (HCC) confirmed histologically or clinically according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.
- Patients with unresectable HCC who have experienced disease progression or treatment discontinuation due to toxicity during prior treatment with lenvatinib.
- Presence of at least one measurable target lesion according to RECIST v1.1.
Key exclusion criteria (10 listed)
- Albumin-bilirubin (ALBI) grade 3.
- Fibrolamellar carcinoma or sarcomatoid carcinoma.
- Prior treatment with regorafenib.
- History of allogeneic stem cell transplantation or solid organ transplantation.
- Active brain metastases or leptomeningeal metastases.
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 |
|---|---|---|
| Regorafenib (BAY 73-4506)"Participants with unresectable hepatocellular carcinoma who have failed prior lenvatinib treatment will receive oral regorafenib. The starting dose for Cycle 1 is 160 mg once daily for patients with Child-Pugh class A, and 120 mg once daily for patients with Child-Pugh class B. From Cycle 2 onwards, regorafenib will be administered at the maximum tolerated dose on a schedule of 3 weeks on and 1 week off (28-day cycle). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. | Drug | Regorafenib |
Primary outcome
progression free survival
Time frame: From date of first dose until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 36 months.
Tumor assessments every 12 weeks (±7 days) after treatment discontinuation without documented progression until progression, death, or end of follow-up, whichever occurs first.
5 secondary outcomes
Overall survival
Time frame: From date of first dose until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 36 months.
time to progression
Time frame: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
objective response rate
Time frame: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
disease control rate
Time frame: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug until 30 days after last dose, assessed up to 24 months.
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 7 Apr 2026.
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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.
Ju Hyun Shim, MD PhD principal investigator
Asan Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib (BAY 73-4506) in people with Carcinoma, Hepatocellular and Lenvatinib, run by Ju Hyun Shim at 1 site in South Korea.
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 19 inclusion and 10 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 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Ju Hyun Shim, MD PhD (82230103190, s5854@amc.seoul.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression free survival (time frame: From date of first dose until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 36 months.). 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 7 Apr 2026.