Clinical trial NCT03418922: A Study of Lenvatinib Plus Nivolumab in Participants With Hepatocellular Carcinoma
Official title: A Phase 1b Trial of Lenvatinib Plus Nivolumab in Subjects With Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2018-02-01
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Cycle length = 28 days)
measure: Part 1 and Part 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug until 30 days after the last dose (up to 53 months)
measure: Mean Change From Baseline in Vital Sign: Weight
timeFrame: Baseline, up to Month 53
measure: Mean Change From Baseline in Vital Sign: Body Mass Index
timeFrame: Baseline, up to Month 53
measure: Mean Change From Baseline in Vital Sign: SpO2 (Oxygen Saturation)
timeFrame: Baseline, up to Month 53
measure: Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values (TEMAVs)
timeFrame: From the first dose of study drug until 30 days after the last dose (up to 53 months)
measure: Number of Participants With Highest Post-Baseline Values for Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Scale
timeFrame: Baseline, up to Month 53
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline, up to Month 53
Secondary outcomes:
measure: Part 1 and Part 2: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Assessed by Investigator Review
timeFrame: From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 52 months)
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for Lenvatinib
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, Tmax: Time to Reach the Cmax for Lenvatinib
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib
timeFrame: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, t1/2: Terminal Elimination Phase Half-Life for Lenvatinib
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, CL/F: Apparent Total Clearance for Lenvatinib
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, Vz/F: Apparent Terminal Volume of Distribution for Lenvatinib
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib
timeFrame: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib
timeFrame: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, Tss,Max: Time to Maximum Observed Concentration at Steady State For Lenvatinib
timeFrame: Cycle 1 Day 15: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, Rac (Cmax): Accumulation Ratio of Cmax for Lenvatinib
timeFrame: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, Rac (AUC0-t): Accumulation Ratio of AUC(0-t) for Lenvatinib
timeFrame: Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)
measure: Part 1, MRT: Mean Residence Time for Lenvatinib
timeFrame: Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: Eisai Trial Site 1
state: Chiba
city: Iizuka
country: Japan
facility: Eisai Trial Site 6
state: Fukuoka
city: Kawasaki
country: Japan
facility: Eisai Trial Site 3
state: Kanagawa
city: Osakasayama
country: Japan
facility: Eisai Trial Site 4
state: Osaka
city: Chuo-ku
country: Japan
facility: Eisai Trial Site 2
state: Tokyo
city: Chiba
country: Japan
facility: Eisai Trial Site 5
Study officials:
References: