Recurrent Hepatocellular CarcinomaPhase 2NCT05103904
Lenvatinib for the Treatment of Recurrent Hepatocellular Carcinoma After Liver Transplant
A Phase 2 study testing Laboratory Biomarker Analysis and Lenvatinib in people with Recurrent Hepatocellular Carcinoma and Stage III Hepatocellular Carcinoma AJCC v8, run by Emory University at 3 sites in United States.
Trial summary
This phase II trial evaluates lenvatinib for the treatment of hepatocellular carcinoma (HCC) that has come back (recurrent) after a liver transplant. HCC is a cancer of the liver and is the second leading cause of cancer-related deaths in the world. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8
- What is being tested?
- Laboratory Biomarker Analysis and Lenvatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 3 sitesUnited States
- Study dates
- 19 Apr 2022to 9 May 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%)
- Patients must have recurrent histologically or cytologically confirmed hepatocellular carcinoma that has recurred after liver transplantation and not amenable for surgical resection
- Child Pugh class A
- Prior orthotropic liver transplantation for curative intent
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- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Life expectancy > 12 weeks as determined by the investigator
- Hemoglobin >= 8.0 g/dl (within 28 days of cycle 1 day 1)
- Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days of cycle 1 day 1; after at least 7 days without growth factor support or transfusion)
- Platelets >= 75,000/mcL (within 28 days of cycle 1 day 1)
- International normalized ratio (INR) =< 2.3 (within 28 days of cycle 1 day 1)
- Total bilirubin =< 3 times the institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 5.0 times the ULN (within 28 days of cycle 1 day 1)
- Albumin >= 2.8 g/dL (within 28 days of cycle 1 day 1)
- Serum creatinine =< 1.5 x ULN or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x ULN; creatinine clearance should be calculated per institutional standard (within 28 days of cycle 1 day 1)
- Urinary protein =< 1+ on dipstick or routine urinalysis or 24-hour urine demonstrating < 1 gram of protein (within 28 days of cycle 1 day 1)
- The effects of lenvatinib on the developing human fetus are unknown. For this reason females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test 72 hours prior to starting protocol therapy. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution.
- Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago
- FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 60 days after the last dose of protocol therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study or for 60 days after the last dose of protocol therapy, she should inform the principal investigator immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 60 days after last dose of protocol therapy.
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) functional classification. To be eligible for this trial, patients should be class 2B or better.
- Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.
- Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.
Who cannot join
- Prior systemic therapy with lenvatinib or another Food and Drug Administration (FDA) approved systemic therapy for hepatocellular carcinoma in the post-transplant setting.
- Prior liver directed therapy is allowed, should be at least > 28 days prior to the study enrollment. Should have at least one measurable untreated lesion by RECIST 1.1 .
- Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1).
- Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Subjects with active hepatitis virus infection controlled with antiviral therapy are eligible.
- Significant cardiovascular impairment: history of congestive heart failure greater than NYHA class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at screening.
- QTc interval > 480 ms
- Uncontrolled blood pressure (systolic blood pressure >140 mmHg or diastolic blood pressure > 90 mmHg) in spite of an optimized regimen of antihypertensive medication.
- Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
- Subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is < 1 g/24 hours.
- Subjects who have not recovered adequately from any toxicity from other anti-cancer treatment regimens and/or complications from major surgery prior to starting therapy. Withhold lenvatinib for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing.
- Females who are breastfeeding or pregnant at screening or baseline (as documented by a positive beta-human chorionic gonadotropin [beta-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 international unites/L or equivalent units of beta-hCG [or hCG]).
- Females of child-bearing potential must be willing to use effective contraception during study and for 60 days after the last dose.
- The participant has severe hypersensitivity (>= grade 3) to lenvatinib and/or any of its excipients.
- Patients with known human immunodeficiency virus (HIV) infection
- Participant with diagnosis, detection, or treatment of another type of cancer =< 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Mayo Clinic Arizona
Scottsdale, Arizona, 85259
About this study
Official title: Lenvatinib in Recurrent Hepatocellular Carcinoma After Liver Transplantation
This phase II trial evaluates lenvatinib for the treatment of hepatocellular carcinoma (HCC) that has come back (recurrent) after a liver transplant. HCC is a cancer of the liver and is the second leading cause of cancer-related deaths in the world. Liver transplantation is a potentially curative treatment option for HCC, however, up to 20% of patients develop recurrent disease after liver transplantation and prognosis remains poor. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Systemic treatments for HCC have not been studied in patients with recurrent HCC after liver transplantation, so there is no established therapy for these patients. This phase II trial evaluates lenvatinib for this purpose.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate anti-tumor activity of the lenvatinib by assessing the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
SECONDARY OBJECTIVES:
- To evaluate the safety and tolerability of lenvatinib in patients with recurrent HCC after liver transplantation.
II. To evaluate the anti-tumor activity of the lenvatinib by assessing progression-free survival (PFS) and overall survival (OS) and duration of response.
TERTIARY/EXPLORATORY OBJECTIVE:
- To assess the effects of the lenvatinib on circulating tumor cells and biomarkers.
OUTLINE:
Patients receive lenvatinib orally (PO) once daily (QD). Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity, or patient withdrawal from the protocol therapy.
After completion of study treatment, patients are followed for 30 days and then every 90 days until death or 2 years from registration.
- Conditions
- Recurrent Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IIIB Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8, Stage IVA Hepatocellular Carcinoma AJCC v8
- Being tested
- Laboratory Biomarker Analysis, Lenvatinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
LenvatinibDrug
Also called E7080, ER-203492-00, Multi-Kinase Inhibitor E7080
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Lenvatinib) | Experimental | Patients receive lenvatinib PO QD. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity, or patient withdrawal from the protocol therapy Receives: Other: Laboratory Biomarker Analysis; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Tumor measurements are performed every 8 weeks. ORR will be calculated as a proportion (complete responses + partial responses / total patients) along with a 95% confidence interval (CI) using the Clopper-Pearson method. Chi-square tests or Fisher's exact tests will be used to compare the efficacy in term of response rate across different groups stratified by biomarkers or other factors, respectively.
Measured: Up to 2 years
Secondary outcomes (3)
Progression-free survival (PFS)
PFS is estimated using the Kaplan-Meier method and compared between different groups using the log-rank test, respectively. The PFS of each patient group is also estimated alone with 95% CI using the Greenwood formula. Cox proportional hazards models are further used in the multivariable analyses to assess the adjusted effect of response on the patients' PFS after adjusting for other factors. Interaction terms between these factors are also tested for statistical significance. The proportional hazards assumption is evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions are addressed by use of time-dependent covariates or extended Cox regression models.
Measured: From diagnosis to disease progression or death, assessed up to 2 years]
Overall survival (OS)
OS is estimated using the Kaplan-Meier method and compared between different groups using the log-rank test, respectively. The OS of each patient group is also estimated alone with 95% CI using the Greenwood formula. Cox proportional hazards models are further used in the multivariable analyses to assess the adjusted effect of response on the patients' OS after adjusting for other factors. Interaction terms between these factors are also tested for statistical significance. The proportional hazards assumption is evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions are addressed by use of time-dependent covariates or extended Cox regression models.
Measured: Time from diagnosis to death, assessed up to 2 years
Duration of response (DR)
Summary statistics are reported for DR including mean, median, standard deviation, and range.
Measured: Time from confirmation of a partial response, complete response, or stable disease until the disease has been shown to progress following treatment, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2021
- Study start19 Apr 2022
- Primary completion9 May 2025
- Study completion9 May 2025
Why it stopped: Slow Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Emory 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Eisai Co., Ltd.
- Responsible party
- Principal investigator, Olumide Gbolahan, Emory University
- Investigators
- Olumide B. Gbolahan, M.D., Principal investigator, Emory University Hospital/Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05103904
- Sponsor's protocol ID
- STUDY00003060
- Other IDs
- NCI-2021-07757, Winship5381-21, P30CA138292
- Status last verified
- Apr 2026
- First submitted
- 11 Oct 2021
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenvatinib in Recurrent Hepatocellular Carcinoma After Liver Transplantation
- ClinicalTrials.gov ID
- NCT05103904
- Acronym / sponsor ID
- STUDY00003060
- Conditions
- Recurrent Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IIIB Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8, Stage IVA Hepatocellular Carcinoma AJCC v8
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Eisai Co., Ltd.
- Study start
- 19 Apr 2022 (actual)
- Primary completion
- 9 May 2025 (actual)
- Study completion
- 9 May 2025 (actual)
- First posted
- 2 Nov 2021 (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.
This phase II trial evaluates lenvatinib for the treatment of hepatocellular carcinoma (HCC) that has come back (recurrent) after a liver transplant. HCC is a cancer of the liver and is the second leading cause of cancer-related deaths in the world. Liver transplantation is a potentially curative treatment option for HCC, however, up to 20% of patients develop recurrent disease after liver transplantation and prognosis remains poor. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Systemic treatments for HCC have not been studied in patients with recurrent HCC after liver transplantation, so there is no established therapy for these patients. This phase II trial evaluates lenvatinib for this purpose.
Detailed description
PRIMARY OBJECTIVE:
- To evaluate anti-tumor activity of the lenvatinib by assessing the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
SECONDARY OBJECTIVES:
- To evaluate the safety and tolerability of lenvatinib in patients with recurrent HCC after liver transplantation.
II. To evaluate the anti-tumor activity of the lenvatinib by assessing progression-free survival (PFS) and overall survival (OS) and duration of response.
TERTIARY/EXPLORATORY OBJECTIVE:
- To assess the effects of the lenvatinib on circulating tumor cells and biomarkers.
OUTLINE:
Patients receive lenvatinib orally (PO) once daily (QD). Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity, or patient withdrawal from the protocol therapy.
After completion of study treatment, patients are followed for 30 days and then every 90 days until death or 2 years from registration.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Lenvatinib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: LenvatinibPatients receive lenvatinib PO QD. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity, or patient withdrawal from the protocol therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Male or female
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%)
- Patients must have recurrent histologically or cytologically confirmed hepatocellular carcinoma that has recurred after liver transplantation and not amenable for surgical resection
- Child Pugh class A
Key exclusion criteria (18 listed)
- Prior systemic therapy with lenvatinib or another Food and Drug Administration (FDA) approved systemic therapy for hepatocellular carcinoma in the post-transplant setting.
- Prior liver directed therapy is allowed, should be at least > 28 days prior to the study enrollment. Should have at least one measurable untreated lesion by RECIST 1.1 .
- Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (i.e., have residual toxicities > grade 1).
- Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (Lenvatinib) |
| LenvatinibAlso: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080Given PO | Drug | Treatment (Lenvatinib) |
Primary outcome
Overall response rate (ORR)
Time frame: Up to 2 years
Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Tumor measurements are performed every 8 weeks. ORR will be calculated as a proportion (complete responses + partial responses / total patients) along with a 95% confidence interval (CI) using the Clopper-Pearson method. Chi-square tests or Fisher's exact tests will be used to compare the efficacy in term of response rate across different groups stratified by biomarkers or other factors, respectively.
3 secondary outcomes
Progression-free survival (PFS)
Time frame: From diagnosis to disease progression or death, assessed up to 2 years]
Overall survival (OS)
Time frame: Time from diagnosis to death, assessed up to 2 years
Duration of response (DR)
Time frame: Time from confirmation of a partial response, complete response, or stable disease until the disease has been shown to progress following treatment, assessed up to 2 years
Results and safety
The study was stopped early (reason given: Slow Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 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. This study is not recruiting at the moment.
Olumide B. Gbolahan, M.D. principal investigator
Emory University Hospital/Winship Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis and Lenvatinib in people with Recurrent Hepatocellular Carcinoma and Stage III Hepatocellular Carcinoma AJCC v8, run by Emory University at 3 sites in United States.
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 24 inclusion and 18 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: stopped early, as of the sponsor's last update on 24 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 3 sites in United States. 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?
The study was stopped early (reason given: Slow Accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: Up to 2 years). 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 24 Apr 2026.