Clinical Trials List
Protocol NumberE7080-G000-304
NCT Number(ClinicalTrials.gov Identfier)NCT01761266
2013-03-31 - 2019-04-30
Phase III
Not yet recruiting12
ICD-10C22.9
Malignant neoplasm of liver, not specified as primary or secondary
A Multicenter, Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable Hepatocellular Carcinoma
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Eisai Inc
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yu-Min Yeh Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- 邱彥程 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Chung-Pin Li Division of Hematology & Oncology
- Ju-Pin Pan Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- Chien-Wei Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Ming-Lun Yeh Digestive System Department
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 曹朝榮 Division of Hematology & Oncology
- 陳昭勳 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
- 林明賢 Division of Hematology & Oncology
- Shang-Wen Chen Division of Hematology & Oncology
- 陳威宇 Division of Hematology & Oncology
- Shang-Hung Chen Division of Hematology & Oncology
- 黃文聰 Division of Hematology & Oncology
- 林建良 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- 呂嘉偉 Division of Radiology
- Wen-Chi Shen Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 劉建廷 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- CHUNG-HSIN CHANG Digestive System Department
- 柯忠旺 Digestive System Department
- 林明賢 Digestive System Department
- 葉宏仁 Digestive System Department
- 李少武 Digestive System Department
- 吳誠中 Division of General Surgery
- CHUN-YING WU Digestive System Department
- 呂宜達 Digestive System Department
- 鄭紹彬 Division of General Surgery
- Sheng-Shun Yang Digestive System Department
- 黃振義 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 陳永芳 Division of General Surgery
- 楊宏仁 Division of General Surgery
- Hsueh-Chou Lai Division of General Surgery
- Po-Heng Chuang Division of General Surgery
- Cheng-Yuan Peng Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- - - Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Unresectable Hepatocellular Carcinoma
Objectives
The primary objective of the study is to compare overall survival (OS) in subjects treated with lenvatinib versus sorafenib as a first-line treatment in subjects with unresectable hepatocellular carcinoma (HCC).
Test Drug
Lenvatinib
Active Ingredient
Lenvatinib
Dosage Form
capsule
Dosage
4mg
Endpoints
Primary Objective:
The primary objective of the study is to compare overall survival (OS) in subjects treated with lenvatinib
versus sorafenib as a first-line treatment in subjects with unresectable hepatocellular carcinoma (HCC).
Secondary Objectives:
● To compare progression-free survival (PFS), time to progression (TTP), and objective response
rate (ORR) of subjects treated with lenvatinib versus sorafenib using modified Response
Evaluation Criteria in Solid Tumors (mRECIST)
● To compare safety and tolerability of subjects treated with lenvatinib versus sorafenib
● To characterize the pharmacokinetics (PK) of lenvatinib using the population approach
● To assess the pharmacokinetics/pharmacodynamics (PD) relationship between exposure and
efficacy/safety
● To compare HCC-specific quality of life (QoL) of subjects treated with lenvatinib versus
sorafenib using the EORTC QLQ-HCC18 questionnaire
The primary objective of the study is to compare overall survival (OS) in subjects treated with lenvatinib
versus sorafenib as a first-line treatment in subjects with unresectable hepatocellular carcinoma (HCC).
Secondary Objectives:
● To compare progression-free survival (PFS), time to progression (TTP), and objective response
rate (ORR) of subjects treated with lenvatinib versus sorafenib using modified Response
Evaluation Criteria in Solid Tumors (mRECIST)
● To compare safety and tolerability of subjects treated with lenvatinib versus sorafenib
● To characterize the pharmacokinetics (PK) of lenvatinib using the population approach
● To assess the pharmacokinetics/pharmacodynamics (PD) relationship between exposure and
efficacy/safety
● To compare HCC-specific quality of life (QoL) of subjects treated with lenvatinib versus
sorafenib using the EORTC QLQ-HCC18 questionnaire
Inclution Criteria
1. Subjects must have confirmed diagnosis of unresectable HCC with any of following criteriao Histologically or cytologically confirmed diagnosis of HCC
o Clinically confirmed diagnosis of HCC according to American Association for the Study of
Liver Diseases (AASLD) criteria, including cirrhosis of any etiology or with chronic hepatitis
B or C infection criteria
2. At least 1 measurable target lesion according to mRECIST meeting the following criteria:
o Hepatic lesion
i. The lesion can be accurately measured in at least one dimension as ≥ 1.0 cm
ii. The lesion is suitable for repeat measurement
iii. The lesion shows intratumoral arterial enhancement on contrast-enhanced computed
tomography (CT) or magnetic resonance imaging (MRI)
o Nonhepatic lesion
i. Lymph node (LN) lesion that measures at least one dimension as ≥ 1.5 cm in the short
axis, except for porta hepatis LN that measures ≥ 2.0 cm in the short axis
ii. Nonnodal lesion that measures ≥ 1.0 cm in the longest diameter
Lesions previously treated with radiotherapy or locoregional therapy must show radiographic
evidence of disease progression to be deemed a target lesion.
3. Subjects categorized to stage B (not applicable for transarterial chemoembolization [TACE]) or
stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
4. Adequate bone marrow function, defined as:
o Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
o Hemoglobin (Hb) ≥ 8.5 g/dL
o Platelet count ≥ 75 × 109/L
5. Adequate liver function, defined as:
o Albumin ≥ 2.8 g/dL
o Bilirubin ≤ 3.0 mg/dL
o Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase
(ALT) ≤ 5 × the upper limit of normal (ULN)
6. Adequate blood coagulation function, defined as international normalized ratio (INR) ≤ 2.3
7. Adequate renal function, defined as creatinine clearance > 30 mL/min calculated per the
Cockcroft and Gault formula
8. Adequate pancreatic function, defined as amylase and lipase ≤ 1.5 × ULN
9. Adequately controlled blood pressure (BP) with 0 or 1 antihypertensive medications, defined as
BP ≤ 150/90 mm Hg at screening and no change in antihypertensive medications within 1 week
prior to the Cycle1/Day1.
10. Child-Pugh score A
11. ECOG-PS 0 or 1
12. Survival expectation of 12 weeks or longer after starting study drug
13. Males or females aged at least 18 years (or any age greater than 18 years as determined by
country legislation) at the time of informed consent
14. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative
beta-human chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of 25 IU/L or
equivalent units of ß-hCG). A separate baseline assessment is required if a negative screening
pregnancy test was obtained more than 72 hours before the first dose of study drug.
15. All females will be considered to be of childbearing potential unless they are postmenopausal
(amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other
known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total
hysterectomy, or bilateral oophorectomy, all with surgery at least one month before dosing).
16. Females of childbearing potential must not have had unprotected sexual intercourse within
30 days before study entry and must agree to use a highly effective method of contraception (e.g.,
total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm
with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner
with confirmed azoospermia) throughout the entire study period and for 30 days after study drug
discontinuation. If currently abstinent, the subject must agree to use a double barrier method as
described above if she becomes sexually active during the study period or for 30 days after study
drug discontinuation. Females who are using hormonal contraceptives must have been on a stable
dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must
continue to use the same contraceptive during the study and for 30 days after study drug
discontinuation.
17. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their
female partners must meet the criteria above (i.e., not of childbearing potential or practicing
highly effective contraception throughout the study period and for 30 days after study drug
discontinuation). No sperm donation is allowed during the study period and for 30 days after
study drug discontinuation.
18. Provide written informed consent
19. Willing and able to comply with all aspects of the protocol
o Clinically confirmed diagnosis of HCC according to American Association for the Study of
Liver Diseases (AASLD) criteria, including cirrhosis of any etiology or with chronic hepatitis
B or C infection criteria
2. At least 1 measurable target lesion according to mRECIST meeting the following criteria:
o Hepatic lesion
i. The lesion can be accurately measured in at least one dimension as ≥ 1.0 cm
ii. The lesion is suitable for repeat measurement
iii. The lesion shows intratumoral arterial enhancement on contrast-enhanced computed
tomography (CT) or magnetic resonance imaging (MRI)
o Nonhepatic lesion
i. Lymph node (LN) lesion that measures at least one dimension as ≥ 1.5 cm in the short
axis, except for porta hepatis LN that measures ≥ 2.0 cm in the short axis
ii. Nonnodal lesion that measures ≥ 1.0 cm in the longest diameter
Lesions previously treated with radiotherapy or locoregional therapy must show radiographic
evidence of disease progression to be deemed a target lesion.
3. Subjects categorized to stage B (not applicable for transarterial chemoembolization [TACE]) or
stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
4. Adequate bone marrow function, defined as:
o Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
o Hemoglobin (Hb) ≥ 8.5 g/dL
o Platelet count ≥ 75 × 109/L
5. Adequate liver function, defined as:
o Albumin ≥ 2.8 g/dL
o Bilirubin ≤ 3.0 mg/dL
o Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase
(ALT) ≤ 5 × the upper limit of normal (ULN)
6. Adequate blood coagulation function, defined as international normalized ratio (INR) ≤ 2.3
7. Adequate renal function, defined as creatinine clearance > 30 mL/min calculated per the
Cockcroft and Gault formula
8. Adequate pancreatic function, defined as amylase and lipase ≤ 1.5 × ULN
9. Adequately controlled blood pressure (BP) with 0 or 1 antihypertensive medications, defined as
BP ≤ 150/90 mm Hg at screening and no change in antihypertensive medications within 1 week
prior to the Cycle1/Day1.
10. Child-Pugh score A
11. ECOG-PS 0 or 1
12. Survival expectation of 12 weeks or longer after starting study drug
13. Males or females aged at least 18 years (or any age greater than 18 years as determined by
country legislation) at the time of informed consent
14. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative
beta-human chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of 25 IU/L or
equivalent units of ß-hCG). A separate baseline assessment is required if a negative screening
pregnancy test was obtained more than 72 hours before the first dose of study drug.
15. All females will be considered to be of childbearing potential unless they are postmenopausal
(amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other
known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total
hysterectomy, or bilateral oophorectomy, all with surgery at least one month before dosing).
16. Females of childbearing potential must not have had unprotected sexual intercourse within
30 days before study entry and must agree to use a highly effective method of contraception (e.g.,
total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm
with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner
with confirmed azoospermia) throughout the entire study period and for 30 days after study drug
discontinuation. If currently abstinent, the subject must agree to use a double barrier method as
described above if she becomes sexually active during the study period or for 30 days after study
drug discontinuation. Females who are using hormonal contraceptives must have been on a stable
dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must
continue to use the same contraceptive during the study and for 30 days after study drug
discontinuation.
17. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their
female partners must meet the criteria above (i.e., not of childbearing potential or practicing
highly effective contraception throughout the study period and for 30 days after study drug
discontinuation). No sperm donation is allowed during the study period and for 30 days after
study drug discontinuation.
18. Provide written informed consent
19. Willing and able to comply with all aspects of the protocol
Exclusion Criteria
1. Imaging findings for HCC corresponding to any of the following:
o HCC with ≥ 50% liver occupation
o Clear invasion into the bile duct
o Portal vein invasion at the main portal branch (Vp4)
2. Subjects who have received any systemic chemotherapy, including sorafenib, or any systemic
investigational anticancer agents, including lenvatinib, for advanced/unresectable HCC. Note:Subjects who have received local hepatic injection chemotherapy are eligible.
3. Subjects who have received any anticancer therapy (including surgery, percutaneous ethanol
injection, radio frequency ablation, transarterial [chemo] embolization, hepatic intra-arterial
chemotherapy, biological, immunotherapy, hormonal, or radiotherapy) or any blood enhancing
treatment (including blood transfusion, blood products, or agents that stimulate blood cell
production, e.g., granulocyte colony-stimulating factor [G-CSF]) within 28 days prior to
randomization
4. Subjects who have not recovered from toxicities as a result of prior anticancer therapy, except
alopecia and infertility. Recovery is defined as < Grade 2 severity per Common Terminology
Criteria for Adverse Events Version 4.0 (CTCAE v4.0).
5. Significant cardiovascular impairment: history of congestive heart failure greater than New York
Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within
6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at
screening
6. Prolongation of QTc interval to > 480 ms
7. Gastrointestinal malabsorption or any other condition that might affect the absorption of
lenvatinib in the opinion of the investigator
8. Bleeding or thrombotic disorders or use of anticoagulants such as, warfarin or similar agents
requiring therapeutic INR monitoring. (Treatment with low molecular weight heparin is allowed.)
9. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomization
10. Gastric or esophageal varices that require treatment
11. Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous
cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months
12. Meningeal carcinomatosis
13. Any history of, or current, brain or subdural metastases
14. Subjects having > 1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for
quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24 h will be ineligible.
15. Arterial-portal venous shunt or arterial-venous shunt preventing proper diagnosis of tumor
16. Any medical or other condition that in the opinion of the investigator would preclude the subject’s
participation in a clinical study
17. Known intolerance to lenvatinib or sorafenib (or any of the excipients)
18. Human immunodeficiency virus (HIV) positive or active infection requiring treatment (except forhepatitis virus)
19. Any history of drug or alcohol dependency or abuse within the prior 2 years
20. Any subject who cannot be evaluated by either triphasic liver CT or triphasic liver MRI because of allergy or other contraindication to both CT and MRI contrast agents
21. Major surgery within 3 weeks prior to randomization or scheduled for surgery during the study
22. Subject has had a liver transplant
o HCC with ≥ 50% liver occupation
o Clear invasion into the bile duct
o Portal vein invasion at the main portal branch (Vp4)
2. Subjects who have received any systemic chemotherapy, including sorafenib, or any systemic
investigational anticancer agents, including lenvatinib, for advanced/unresectable HCC. Note:Subjects who have received local hepatic injection chemotherapy are eligible.
3. Subjects who have received any anticancer therapy (including surgery, percutaneous ethanol
injection, radio frequency ablation, transarterial [chemo] embolization, hepatic intra-arterial
chemotherapy, biological, immunotherapy, hormonal, or radiotherapy) or any blood enhancing
treatment (including blood transfusion, blood products, or agents that stimulate blood cell
production, e.g., granulocyte colony-stimulating factor [G-CSF]) within 28 days prior to
randomization
4. Subjects who have not recovered from toxicities as a result of prior anticancer therapy, except
alopecia and infertility. Recovery is defined as < Grade 2 severity per Common Terminology
Criteria for Adverse Events Version 4.0 (CTCAE v4.0).
5. Significant cardiovascular impairment: history of congestive heart failure greater than New York
Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within
6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at
screening
6. Prolongation of QTc interval to > 480 ms
7. Gastrointestinal malabsorption or any other condition that might affect the absorption of
lenvatinib in the opinion of the investigator
8. Bleeding or thrombotic disorders or use of anticoagulants such as, warfarin or similar agents
requiring therapeutic INR monitoring. (Treatment with low molecular weight heparin is allowed.)
9. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomization
10. Gastric or esophageal varices that require treatment
11. Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous
cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months
12. Meningeal carcinomatosis
13. Any history of, or current, brain or subdural metastases
14. Subjects having > 1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for
quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24 h will be ineligible.
15. Arterial-portal venous shunt or arterial-venous shunt preventing proper diagnosis of tumor
16. Any medical or other condition that in the opinion of the investigator would preclude the subject’s
participation in a clinical study
17. Known intolerance to lenvatinib or sorafenib (or any of the excipients)
18. Human immunodeficiency virus (HIV) positive or active infection requiring treatment (except forhepatitis virus)
19. Any history of drug or alcohol dependency or abuse within the prior 2 years
20. Any subject who cannot be evaluated by either triphasic liver CT or triphasic liver MRI because of allergy or other contraindication to both CT and MRI contrast agents
21. Major surgery within 3 weeks prior to randomization or scheduled for surgery during the study
22. Subject has had a liver transplant
The Estimated Number of Participants
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Taiwan
75 participants
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Global
1450 participants
