A Study of Lenvatinib Plus Nivolumab in Participants With Hepatocellular Carcinoma

December 28, 2023 updated by: Eisai Co., Ltd.

A Phase 1b Trial of Lenvatinib Plus Nivolumab in Subjects With Hepatocellular Carcinoma

The primary objective of this study is to evaluate the tolerability and safety of a combination of lenvatinib plus nivolumab in participants with hepatocellular carcinoma (HCC).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Chiba, Japan
        • EISAI Trial Site 5
    • Chiba
      • Kashiwa, Chiba, Japan
        • EISAI Trial Site 1
    • Fukuoka
      • Iizuka, Fukuoka, Japan
        • EISAI Trial Site 6
    • Kanagawa
      • Kawasaki, Kanagawa, Japan
        • EISAI Trial Site 3
    • Osaka
      • Osakasayama, Osaka, Japan
        • EISAI Trial Site 4
    • Tokyo
      • Chuo-ku, Tokyo, Japan
        • EISAI Trial Site 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must have confirmed diagnosis of hepatocellular carcinoma (HCC) with any of the following criteria:

    • Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
    • Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection
  • Part 1: HCC for which no other appropriate therapy is available; Part 2: No prior systemic therapy for advanced/unresectable HCC
  • Participants categorized to stage B (not applicable for transarterial chemoembolization), or stage C based on Barcelona Clinic Liver Cancer staging system
  • Child-Pugh score A
  • Participants must have an Eastern Cooperative Oncology Group Performance Status of 0 to 1
  • Age greater than or equal to (>=) 20 years at the time of informed consent

Exclusion Criteria:

  • Active co-infection with hepatitis B and hepatitis C
  • Participants with any active, known, or suspected autoimmune disease
  • Participants being treated with drugs that strongly inhibit or induce CYP3A4 and that may be possibly used during this study
  • Females who are breastfeeding or pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1: Lenvatinib Plus Nivolumab
Participants will receive specified doses of lenvatinib (oral) and nivolumab (intravenous) on specified days.
Drug: Lenvatinib
Specified doses will be administered orally on specified days.
Drug: Nivolumab
Specified doses will be administered intravenously on specified days.
Experimental: Part 2: Lenvatinib Plus Nivolumab
If tolerable in Part 1, participants will receive specified doses of lenvatinib and nivolumab on specified days until criteria for discontinuation are met.
Drug: Lenvatinib
Specified doses will be administered orally on specified days.
Drug: Nivolumab
Specified doses will be administered intravenously on specified days.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (Cycle length = 28 days)
DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following hematological or non-hematological toxicities considered to be at least possibly related to lenvatinib and/or nivolumab occurring during Cycle 1: 1) Febrile neutropenia or Grade 4 neutropenia for >7 days; 2) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 3) Grade 4 anemia; 4) Clinical deterioration manifested by drug-related hepatic decompensation; 5) >=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted; 6) Other Grade 3 toxicity lasting >3 days or Grade 4 non-hematological toxicity of any duration; 7) Grade 2 uveitis, eye pain, or blurred vision that did not respond to topical therapy; 8) Failure to administer 8 or more dose of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity.
Cycle 1 (Cycle length = 28 days)
Part 1 and Part 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From the first dose of study drug until 30 days after the last dose (up to 53 months)
A TEAE was defined as an adverse event (AE) that emerged during treatment and until the 30 days after the last dose or until the participants initiated new anticancer therapy, whichever was earlier, was absent at pretreatment (Baseline) or reemerged during treatment, was present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening (that is, participant was at immediate risk of death from AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).
From the first dose of study drug until 30 days after the last dose (up to 53 months)
Mean Change From Baseline in Vital Sign: Weight
Time Frame: Baseline, up to Month 53
Mean change from baseline in weight were evaluated.
Baseline, up to Month 53
Mean Change From Baseline in Vital Sign: Body Mass Index
Time Frame: Baseline, up to Month 53
Mean change from baseline in body mass index were evaluated.
Baseline, up to Month 53
Mean Change From Baseline in Vital Sign: SpO2 (Oxygen Saturation)
Time Frame: Baseline, up to Month 53
Mean change from baseline in SpO2 were evaluated.
Baseline, up to Month 53
Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values (TEMAVs)
Time Frame: From the first dose of study drug until 30 days after the last dose (up to 53 months)
Treatment-emergent markedly abnormal laboratory value was defined as a postbaseline laboratory value with grade 3 or higher, and with a grade increase from baseline, (that is [i.e.] increasing grade 0 to 3 or higher, grade 1 to 3 or higher, grade 2 to 3 or higher, grade 3 to 4 or 5, grade 4 to 5). Test abnormalities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 =mild; Grade 2 =moderate; Grade 3/Grade 4 =severe/life-threatening, Grade 5 =death.
From the first dose of study drug until 30 days after the last dose (up to 53 months)
Number of Participants With Highest Post-Baseline Values for Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Scale
Time Frame: Baseline, up to Month 53
Performance status assessments were based on 5-grade ECOG scale (from 0 to 4), where 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work); 2=ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5=dead.
Baseline, up to Month 53
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Time Frame: Baseline, up to Month 53
Change from baseline in left ventricular ejection fraction (LVEF) were evaluated by multigated acquisition scan (MUGA) or echocardiogram.
Baseline, up to Month 53

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1 and Part 2: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Assessed by Investigator Review
Time Frame: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 52 months)
ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on mRECIST assessed by investigator review. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is less than 10 millimeters [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of diameter of all target lesions without unequivocal progression of all non-target lesions, as compared with Baseline.
From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 52 months)
Part 1, Cmax: Maximum Observed Plasma Concentration for Lenvatinib
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Cmax was defined as the maximum plasma concentration for lenvatinib. Cmax was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Part 1, Tmax: Time to Reach the Cmax for Lenvatinib
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Tmax was defined as the time to reach maximum observed plasma concentration (Cmax) for lenvatinib. Tmax was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Part 1, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib
Time Frame: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
AUC(0-t) was defined as the area under the plasma concentration-time curve from 0 time to last measurable point for lenvatinib. AUC(0-t) was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
Part 1, AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
AUC(0-Inf) was defined as the area under the plasma concentration-time curve from 0 to infinity for lenvatinib. AUC(0-Inf) was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Part 1, t1/2: Terminal Elimination Phase Half-Life for Lenvatinib
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
t1/2 was defined as the terminal elimination phase half-life for lenvatinib. t1/2 was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Part 1, CL/F: Apparent Total Clearance for Lenvatinib
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as (Dose/AUC(0-inf))/F. Where AUC(0-inf) is the area under the plasma concentration-time curve from zero to infinity and F is the bioavailability of the drug.
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Part 1, Vz/F: Apparent Terminal Volume of Distribution for Lenvatinib
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was calculated as (CL/F)/Lambda Z. Where, CL/F is the apparent total clearance and lambda Z is the apparent terminal elimination rate constant.
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Part 1, Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib
Time Frame: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
Css,max was defined as the maximum plasma concentration at steady state for lenvatinib. Css,max was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
Part 1, Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib
Time Frame: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
Css,min is the minimum plasma concentration at steady state for lenvatinib. Css,min was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
Part 1, Tss,Max: Time to Maximum Observed Concentration at Steady State For Lenvatinib
Time Frame: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
Tss,Max was defined as the time to reach maximum observed plasma concentration of lenvatinib at steady state. Tss,Max was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
Part 1, Rac (Cmax): Accumulation Ratio of Cmax for Lenvatinib
Time Frame: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
Rac(Cmax) was calculated as Css,max at Cycle 1 Day 15/Cmax at Cycle 1 Day 1.
Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
Part 1, Rac (AUC0-t): Accumulation Ratio of AUC(0-t) for Lenvatinib
Time Frame: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
Rac(AUC) was calculated as AUC(0-t) at Cycle 1 Day 15/AUC(0-t) at Cycle 1 Day 1.
Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
Part 1, MRT: Mean Residence Time for Lenvatinib
Time Frame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
MRT was derived by non-compartmental analysis using lenvatinib plasma concentrations.
Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Co., Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ono Pharmaceutical Co. Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 16, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 28, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 28, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 26, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 1, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 28, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E7080-J081-117

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoma, Hepatocellular

Clinical Trials on Lenvatinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings