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Carcinoma, HepatocellularPhase 1NCT03418922

A Study of Lenvatinib Plus Nivolumab in Participants With Hepatocellular Carcinoma

A Phase 1 study testing Lenvatinib and Nivolumab in people with Carcinoma, Hepatocellular, run by Eisai Co., Ltd. at 6 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
Lenvatinib and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
6 sitesJapan
Study dates
16 Jan 2018to 28 Dec 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Japan6 sites

  • Eisai Trial Site 5

    Chiba

  • Eisai Trial Site 2

    Chuo-ku, Tokyo

  • Eisai Trial Site 6

    Iizuka, Fukuoka

  • Eisai Trial Site 1

    Kashiwa, Chiba

  • Eisai Trial Site 3

    Kawasaki, Kanagawa

  • Eisai Trial Site 4

    Sayama, Osaka

Other trials in Japan

About this study

Official title: 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).

Being tested
Lenvatinib, Nivolumab
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    Specified doses will be administered orally on specified days.

  • NivolumabDrug

    Specified doses will be administered intravenously on specified days.

Study groups in NCT03418922
Study groupRoleWhat they receive
Part 1: Lenvatinib Plus NivolumabExperimentalParticipants will receive specified doses of lenvatinib (oral) and nivolumab (intravenous) on specified days.
Receives: Drug: Lenvatinib; Drug: Nivolumab
Part 2: Lenvatinib Plus NivolumabExperimentalIf tolerable in Part 1, participants will receive specified doses of lenvatinib and nivolumab on specified days until criteria for discontinuation are met.
Receives: Drug: Lenvatinib; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

    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.

    Measured: Cycle 1 (Cycle length = 28 days)

  2. Part 1 and Part 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    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).

    Measured: From the first dose of study drug until 30 days after the last dose (up to 53 months)

  3. Mean Change From Baseline in Vital Sign: Weight

    Mean change from baseline in weight were evaluated.

    Measured: Baseline, up to Month 53

  4. Mean Change From Baseline in Vital Sign: Body Mass Index

    Mean change from baseline in body mass index were evaluated.

    Measured: Baseline, up to Month 53

  5. Mean Change From Baseline in Vital Sign: SpO2 (Oxygen Saturation)

    Mean change from baseline in SpO2 were evaluated.

    Measured: Baseline, up to Month 53

  6. Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values (TEMAVs)

    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.

    Measured: From the first dose of study drug until 30 days after the last dose (up to 53 months)

  7. Number of Participants With Highest Post-Baseline Values for Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Scale

    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.

    Measured: Baseline, up to Month 53

  8. Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

    Change from baseline in left ventricular ejection fraction (LVEF) were evaluated by multigated acquisition scan (MUGA) or echocardiogram.

    Measured: Baseline, up to Month 53

Secondary outcomes (14)

  1. Part 1 and Part 2: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Assessed by Investigator Review

    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.

    Measured: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 52 months)

  2. Part 1, Cmax: Maximum Observed Plasma Concentration for Lenvatinib

    Cmax was defined as the maximum plasma concentration for lenvatinib. Cmax was derived by non-compartmental analysis using lenvatinib plasma concentrations.

    Measured: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

  3. Part 1, Tmax: Time to Reach the Cmax for Lenvatinib

    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.

    Measured: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

  4. Part 1, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib

    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.

    Measured: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)

  5. Part 1, AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib

    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.

    Measured: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

  6. Part 1, t1/2: Terminal Elimination Phase Half-Life for Lenvatinib

    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.

    Measured: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

  7. Part 1, CL/F: Apparent Total Clearance for Lenvatinib

    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.

    Measured: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

  8. Part 1, Vz/F: Apparent Terminal Volume of Distribution for Lenvatinib

    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.

    Measured: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

  9. Part 1, Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib

    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.

    Measured: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)

  10. Part 1, Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib

    Css,min is the minimum plasma concentration at steady state for lenvatinib. Css,min was derived by non-compartmental analysis using lenvatinib plasma concentrations.

    Measured: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)

  11. Part 1, Tss,Max: Time to Maximum Observed Concentration at Steady State For Lenvatinib

    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.

    Measured: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)

  12. Part 1, Rac (Cmax): Accumulation Ratio of Cmax for Lenvatinib

    Rac(Cmax) was calculated as Css,max at Cycle 1 Day 15/Cmax at Cycle 1 Day 1.

    Measured: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)

  13. Part 1, Rac (AUC0-t): Accumulation Ratio of AUC(0-t) for Lenvatinib

    Rac(AUC) was calculated as AUC(0-t) at Cycle 1 Day 15/AUC(0-t) at Cycle 1 Day 1.

    Measured: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)

  14. Part 1, MRT: Mean Residence Time for Lenvatinib

    MRT was derived by non-compartmental analysis using lenvatinib plasma concentrations.

    Measured: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2018
  2. Study start16 Jan 2018
  3. Primary completion28 Dec 2022
  4. Study completion28 Dec 2022

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03418922
Sponsor's protocol ID
E7080-J081-117
Status last verified
May 2022
First submitted
26 Jan 2018
Last updated
20 Jun 2024
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lenvatinib and Nivolumab in people with Carcinoma, Hepatocellular, run by Eisai Co., Ltd. at 6 sites in Japan.

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 8 inclusion and 4 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: finished, as of the sponsor's last update on 20 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Japan. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1 (Cycle length = 28 days)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03418922.

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 20 Jun 2024.

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