Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

In the Dose-Escalation Component of the study, lenvatinib will be administered as continuous once-daily oral dosing. Dose-escalation will occur based on safety information obtained during Cycle 1. The recommended dose for the Expansion Component of the study will use the MTD in Cycle 1.

The purpose of this study is to determine maximum tolerated dose (MTD), efficacy, safety and tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor effect of E7080 when is administered continually once daily in participants with advanced hepatocellular carcinoma.

Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)

Phase I/II Study of E7080 in Patients With Advanced Hepatocellular Carcinoma (HCC)

The MTD was defined as the highest dose level at which no more than 1 of 6 participants had a dose limiting toxicities (DLT). DLT was defined as any of the following events: grade 4 or higher hematologic toxicity or grade 3 thrombocytopenia that required blood transfusion, grade 3 or higher nonhematologic toxicity, grade 4 hypertension uncontrolled by antihypertensive drug(s), aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than (\>) 10.0\*upper limit of normal (ULN), proteinuria 4+ by urine dipstick, proteinuria 3+ by urine dipstick was to be monitored by 24-hour urine collection, proteinuria \>3.5 gram (g) for 24 hours, diarrhea/vomiting/nausea of grade 3 or higher that was uncontrollable despite maximal supportive therapies and abnormal clinical laboratory values that required no treatment, grade 3 proteinuria by dipstick, diarrhea/vomiting/nausea that was managed with supportive therapies were not considered as DLT.

TTP was defined as the time from the date of registration to the date when progressive disease (PD) was first confirmed. PD was evaluated according to modified response evaluation criteria in solid tumors (mRECIST) by an independent imaging review. PD was defined as at least a 20 percent (%) increase in the sum of long diameter (LD) of target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 millimeter (mm) (including new lesions).

BOR was performed using RECIST1.1 and was measured as complete response (CR) defined as when an overall response of CR was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of CR was confirmed and the BOR established as CR was regarded as the "CR confirmed date), partial response (PR) defined as when the overall response of PR or better (CR or PR) was obtained 2 or more consecutive times at intervals of at least 28 days (the date when the second overall response of PR was confirmed and the BOR established as PR will be regarded as the "PR confirmed date), PD defined as when the BOR was neither CR, PR, or stable disease (SD), and the overall response was PD, SD defined as when the BOR obtained was neither CR nor PR, but no PD from the initial administration to the end of Cycle 2 and the overall response of SD or better occurred at least once and not evaluable (NE) was when the overall response was NE in all cases.

ORR was defined as the percentage of participants who achieved a tumor response measured by RECIST 1.1 of CR defined as disappearance of all target lesions (a short diameter is less than (\<)10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

DCR was measured by RECIST 1.1 and defined as CR which was defined as disappearance of all target lesions (a short diameter was \<10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.

PFS was defined as the time from the date of registration until the date when PD was first confirmed or death (whichever occurred first) as determined by mRECIST and PD was defined as at least a 20% increase in the sum of long diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.

ORR was defined as the percentage of participants who achieved a tumor response measured by mRECIST of CR defined as disappearance of all target lesions (a short diameter is \<10 mm if it exists in a lymph node) plus PR defined as at least 30% decrease in the sum of the long diameter LD (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

DCR was measured by mRECIST and defined as CR which was defined as disappearance of all target lesions (a short diameter is \<10 mm if it exists in a lymph node) plus PR which was defined as at least 30% decrease in the sum of the long diameter (hereafter referred to as sum of LD) of all target lesions, as compared with baseline summed LD plus SD which was reduction in tumor volume of less than 50% or an increase in the volume of 1 or more measurable lesions of less than 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to PD.

OS was defined as the time from the date of registration until the date of death.

Eisai Co., Ltd.

Participants with child CP scores of 5 or 6 received a starting dose of 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.

Phase 1: Group 1: Lenvatinib: 12 mg

Participants with CP scores of 5 or 6 received 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.

Phase 1: Group 1: Lenvatinib: 16 mg

Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group 1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.

Phase 1: Group 2: Lenvatinib: 8 mg

Participants with CP scores of 7 or 8 received 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.

Phase 1: Group 2: Lenvatinib: 12 mg

Participants with CP scores of 5 or 6 received lenvatinib RD of 12 mg (three 4 mg tablets) established from group 1 in the dose escalation component (Phase1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.

Phase 2: Lenvatinib: 12 mg

Participants with CP scores of 5 or 6 received a starting dose of 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.

Participants with CP scores of 5 or 6 received RD of 12 mg (three 4 mg tablets) lenvatinib established from group 1, in the dose escalation component (phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.

Total

>=37 years and <=80 years

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

All participants who received at least 1 dose of lenvatinib, and had at least 1 post baseline efficacy evaluation.

Eisai Medical Services

Participants with CP scores of 5 or 6 received 12 mg (three 4 mg tablets) or 16 mg (four 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating.

Phase 1: Group 1: Levatinib 12 or 16 mg (CP Score 5 or 6)

Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) or 12 mg (three 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.

Phase 1: Group 2: Lenvatinib 8 or 12 mg (CP Score 7 or 8)

Safety analysis set (SAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 post baseline safety evaluation.

Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib

Participants with CP scores of 5 or 6 received lenvatinib RD of 12 mg (three 4 mg tablets) established from group 1 in the dose escalation component (Phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.

Phase 2 : Lenvatinib :12 mg

Per protocol set (PPS) included all participants in full analysis set (FAS), who showed greater than or equal to (\>=) 75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.

Phase 2: Time to Progression (TTP) by Independent Review Assessment

Phase 1: Group1: Lenvatinib: 16 mg

Participants with CP scores of 7 or 8 received 8 mg (two 4 mg tablets) lenvatinib orally QD in a 28-day treatment cycle which was the lowest dose at which tolerability was confirmed in group1, was used as the starting dose in the dose-determination scheme (group 2) on an empty stomach or at least 1 hour after eating.

Efficacy analysis set (EAS) included all participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.

Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment

EAS included participants who received at least 1 dose of lenvatinib, and had at least 1 postbaseline efficacy evaluation.

Phase 1: Objective Response Rate (ORR) by Investigator Assessment

Phase 1: Disease Control Rate (DCR) by Investigator Assessment

Participants with CP scores of 5 or 6 received RD of 12 mg (three 4 mg tablets) lenvatinib established from group 1 in the dose escalation component (phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.

PPS included all participants in the FAS who showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.

Phase 2: Progression-free Survival (PFS) by Independent Review Assessment

Phase 2: Objective Response Rate (ORR) by Independent Review Assessment

Week 8

Week 16

Participants with CP scores of 5 or 6 received RD of 12 mg (three 4 mg tablets) lenvatinib established from group 1 in the dose escalation component (Phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.

PPS included all participants in the FAS showed \>=75% cumulative treatment compliance, had a baseline and post baseline tumor response assessment, and completed at least 2 cycles or discontinued during the 2 cycles due to PD or death.

Phase 2: Disease Control Rate (DCR) by Independent Review Assessment

Phase 2: Overall Survival (OS)

Participants with child-pugh (CP) scores of 5 or 6 received a starting dose of 12 milligram (mg) (three 4 mg tablets) lenvatinib orally once daily (QD) in a 28-day treatment cycle in the dose-escalation scheme (group 1) on an empty stomach or at least 1 hour after eating until the tolerated dose was achieved.

Participants with CP scores of 5 or 6 received recommended dose (RD) of 12 mg (three 4 mg tablets) lenvatinib established from group 1, in the dose escalation component (phase 1) study, orally QD in a 28-day treatment cycle in dose expansion component on an empty stomach or at least 1 hour after eating.

Spots Global Cancer Trial Database for Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)

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