Lenvatinib for the Treatment of Recurrent Hepatocellular Carcinoma After Liver Transplant

NCT05103904 | Terminated Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00003060NCI-2021-07757Winship5381-21P30CA138292
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Stage IV Hepatocellular Carcinoma AJCC v8; Stage IVA Hepatocellular Carcinoma AJCC v8; Unresectable Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma AJCC v8; Stage IVB Hepatocellular Carcinoma AJCC v8; Recurrent Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma AJCC v8; Stage III Hepatocellular Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (3)

• Progression-free survival (PFS)

  From diagnosis to disease progression or death, assessed up to 2 years]

• Overall survival (OS)

  Time from diagnosis to death, assessed up to 2 years

• Duration of response (DR)

  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

Study Arms (1)

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

Other: Laboratory Biomarker Analysis; Drug: Lenvatinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Lenvatinib)

Lenvatinib DRUG

Given PO

Also known as: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Treatment (Lenvatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator
• Eisai Co., Ltd.: collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Olumide B. Gbolahan, M.D.

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: November 2, 2021
• Study Start: April 19, 2022
• Primary Completion: May 9, 2025
• Study Completion: May 9, 2025
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (3)