Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Lenvatinib
Sponsored by

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Carcinoma, Hepatocellular
Eligibility Criteria
Inclusion criteria:
- Histologically or clinically confirmed diagnosis of advanced HCC.
- Eastern Cooperative Oncology Group-Performance Status (ECOG-PS): 0-1.
- Adequate laboratory values/organ function tests.
Exclusion criteria:
- Simultaneous or metachronous cancers.
- Pericardial, ascites, or pleural effusion requiring drainage.
- Brain metastasis/meningeal carcinomatosis presenting clinical symptoms or requiring treatment.
- Malabsorption syndrome.
- Artery-portal vein shunt or artery-vein shunt preventing proper diagnosis of tumor.
- Use of drugs known to inhibit cytochrome P3A4.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lenvatinib
Arm Description
Outcomes
Primary Outcome Measures
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib
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.
Phase 2: Time to Progression (TTP) by Independent Review Assessment
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).
Secondary Outcome Measures
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
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.
Phase 1: Objective Response Rate (ORR) by Investigator Assessment
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.
Phase 1: Disease Control Rate (DCR) by Investigator Assessment
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.
Phase 2: Progression-free Survival (PFS) by Independent Review Assessment
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.
Phase 2: Objective Response Rate (ORR) by Independent Review Assessment
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.
Phase 2: Disease Control Rate (DCR) by Independent Review Assessment
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.
Phase 2: Overall Survival (OS)
OS was defined as the time from the date of registration until the date of death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00946153
Brief Title
Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)
Official Title
Phase I/II Study of E7080 in Patients With Advanced Hepatocellular Carcinoma (HCC)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
July 24, 2009 (Actual)
Primary Completion Date
June 15, 2014 (Actual)
Study Completion Date
August 13, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Co., Ltd.
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Carcinoma, Hepatocellular
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lenvatinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Other Intervention Name(s)
E7080
Intervention Description
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.
Primary Outcome Measure Information:
Title
Phase 1: Maximum Tolerated Dose (MTD) of Lenvatinib
Description
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.
Time Frame
Up to 28 days (Cycle1)
Title
Phase 2: Time to Progression (TTP) by Independent Review Assessment
Description
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).
Time Frame
From day of registration to the day when PD was first confirmed (approximately up to 6.1 years)
Secondary Outcome Measure Information:
Title
Phase 1: Best Overall Response (BOR) of Lenvatinib by Investigator Assessment
Description
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.
Time Frame
Every 8 weeks (approximately up to 18.4 months)
Title
Phase 1: Objective Response Rate (ORR) by Investigator Assessment
Description
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.
Time Frame
From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Title
Phase 1: Disease Control Rate (DCR) by Investigator Assessment
Description
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.
Time Frame
Up to Week 16
Title
Phase 2: Progression-free Survival (PFS) by Independent Review Assessment
Description
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.
Time Frame
From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Title
Phase 2: Objective Response Rate (ORR) by Independent Review Assessment
Description
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.
Time Frame
From day of registration to the day when PD was first confirmed or death (approximately 6.1 years)
Title
Phase 2: Disease Control Rate (DCR) by Independent Review Assessment
Description
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.
Time Frame
Weeks 8 and 16
Title
Phase 2: Overall Survival (OS)
Description
OS was defined as the time from the date of registration until the date of death.
Time Frame
From day of registration to the day of death (approximately 6.1 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Histologically or clinically confirmed diagnosis of advanced HCC.
Eastern Cooperative Oncology Group-Performance Status (ECOG-PS): 0-1.
Adequate laboratory values/organ function tests.
Exclusion criteria:
Simultaneous or metachronous cancers.
Pericardial, ascites, or pleural effusion requiring drainage.
Brain metastasis/meningeal carcinomatosis presenting clinical symptoms or requiring treatment.
Malabsorption syndrome.
Artery-portal vein shunt or artery-vein shunt preventing proper diagnosis of tumor.
Use of drugs known to inhibit cytochrome P3A4.
Facility Information:
City
Kashiwa-shi
State/Province
Chiba
Country
Japan
City
Kurume-shi
State/Province
Fukuoka
Country
Japan
City
Sapporo-shi
State/Province
Hokkaido
Country
Japan
City
Kawasaki-shi
State/Province
Kanagawa
Country
Japan
City
Osaka-shi
State/Province
Osaka
Country
Japan
City
Osakasayama-shi
State/Province
Osaka
Country
Japan
City
Saga-shi
State/Province
Saga
Country
Japan
City
Chuo-ku
State/Province
Tokyo
Country
Japan
City
Minato-ku
State/Province
Tokyo
Country
Japan
City
Musashino-shi
State/Province
Tokyo
Country
Japan
City
Gangnam-gu
State/Province
Seoul
Country
Korea, Republic of
City
Songpa-gu
State/Province
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
27704266
Citation
Ikeda K, Kudo M, Kawazoe S, Osaki Y, Ikeda M, Okusaka T, Tamai T, Suzuki T, Hisai T, Hayato S, Okita K, Kumada H. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol. 2017 Apr;52(4):512-519. doi: 10.1007/s00535-016-1263-4. Epub 2016 Oct 4.
Results Reference
derived
Learn more about this trial
Study of Lenvatinib (E7080) in Participants With Advanced Hepatocellular Carcinoma (HCC)
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