Clinical Trials List
Protocol NumberE7080-G000-209
2013-02-15 - 2014-04-18
Phase II
Terminated4
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Multicenter, Open-Label Phase 2 Study of the Safety and Activity of Lenvatinib (E7080) in Subjects With KIF5B-RET-Positive Adenocarcinoma of the Lung
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Eisai Limited
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 徐偉勛 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Adenocarcinoma of the Lung
Objectives
Primary Objective:
To evaluate the objective response rate (ORR) in subjects treated with lenvatinib in KIF5B-RET-positive adenocarcinoma of the lung.
Secondary Objectives:
To evaluate the safety and tolerability of lenvatinib in subjects with KIF5B-RET-positive adenocarcinoma of the lung.
To evaluate the following efficacy endpoints in subjects treated with lenvatinib in KIF5B-RET-positive adenocarcinoma of the lung:
o Progression free survival (PFS)
o Overall survival (OS)
To evaluate pharmacokinetics of lenvatinib in subjects with adenocarcinoma of the lung.
Test Drug
E7080
Active Ingredient
E7080
Dosage Form
capsule
Dosage
4
Endpoints
Primary Endpoint:
- Objective response rate (ORR), defined as the proportion of subjects who have best overall response of CR or PR based on investigator tumor assessment.
Secondary Endpoints:
- Progression-free survival (PFS): defined as the time from the first dose to the date of first documentation of disease progression, or date of death, whichever occurs first. PFS censoring rules will be defined in the statistical analysis plan (SAP) and follow FDA guidance.
- Overall survival (OS): defined as the time from the date of first dose to the date of death from any cause. Subjects who are alive at the date of the data cutoff will be censored at the cutoff day. Subjects who are lost to follow-up will be censored at the date the subject was last known to be alive.
- Pharmacokinetics: as measured by plasma PK lenvatinib exposure parameters.
Exploratory Endpoints:
- Disease control rate (DCR): defined as the proportion of subjects who have best overall response of confirmed CR, or PR, or SD. Best overall response of SD must be at least 7 weeks after the first dose of lenvatinib.
- Clinical benefit rate (CBR): defined as proportion of subjects who have best overall response of confirmed CR, or PR, or durable SD. Durable SD must be at least 23 weeks after the first dose of lenvatinib.
- Time to response (TTR): defined as the time from the date of first dose to the date when a confirmed response was first recorded.
- Duration of response (DOR): defined as the time from the date a response was first documented until the date of the first documentation of disease progression or date of death from any cause.
- Subject-reported health outcome (HSU): defined as the utility scores calculated based on the subject-reported health outcome questionnaires, including QLQ-C30, QLQ-L13, EQ-5D and HSU.
- Objective response rate (ORR), defined as the proportion of subjects who have best overall response of CR or PR based on investigator tumor assessment.
Secondary Endpoints:
- Progression-free survival (PFS): defined as the time from the first dose to the date of first documentation of disease progression, or date of death, whichever occurs first. PFS censoring rules will be defined in the statistical analysis plan (SAP) and follow FDA guidance.
- Overall survival (OS): defined as the time from the date of first dose to the date of death from any cause. Subjects who are alive at the date of the data cutoff will be censored at the cutoff day. Subjects who are lost to follow-up will be censored at the date the subject was last known to be alive.
- Pharmacokinetics: as measured by plasma PK lenvatinib exposure parameters.
Exploratory Endpoints:
- Disease control rate (DCR): defined as the proportion of subjects who have best overall response of confirmed CR, or PR, or SD. Best overall response of SD must be at least 7 weeks after the first dose of lenvatinib.
- Clinical benefit rate (CBR): defined as proportion of subjects who have best overall response of confirmed CR, or PR, or durable SD. Durable SD must be at least 23 weeks after the first dose of lenvatinib.
- Time to response (TTR): defined as the time from the date of first dose to the date when a confirmed response was first recorded.
- Duration of response (DOR): defined as the time from the date a response was first documented until the date of the first documentation of disease progression or date of death from any cause.
- Subject-reported health outcome (HSU): defined as the utility scores calculated based on the subject-reported health outcome questionnaires, including QLQ-C30, QLQ-L13, EQ-5D and HSU.
Inclution Criteria
1. Subjects must have a cytological or histological confirmed diagnosis of adenocarcinoma of the lung.
2. Subjects must have tumors expressing the KIF5B-RET translocation as detected by gene sequencing, or other confirmed RET translocations (e.g., CCDC6-RET).
3. Subjects may have received up to three prior systemic anticancer treatment regimens for adenocarcinoma of the lung (including adjuvant therapies and tyrosine-kinase inhibitors [TKI]), unless discussed with the sponsor.
4. Subjects must have a clinically indicated need for systemic chemotherapy for adenocarcinoma of the lung based on the investigator’s assessment.
5. Presence of measurable disease meeting the following criteria:
a. At least one lesion of at least 1.0 cm in the long-axis diameter for a non-lymph node or at least 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) using either
computerized tomography (CT) or magnetic resonance imaging (MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of at least 1.5 cm.
b. Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
6. Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection will be eligible if they have remained clinically stable, asymptomatic and off of steroids for 28 days.
7. Adequate bone marrow function.
8.Adequate liver function.
9.Adequate renal function, defined as calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula.
10.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1/Day 1 (C1D1).
11.Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) of 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 (Screen 1).
14.Females must not be breast-feeding 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.
17. Male subjects must have had a successful vasectomy y (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 (Screen 1 and Screen 2)
19. Willing and able to comply with all aspects of the protocol.
2. Subjects must have tumors expressing the KIF5B-RET translocation as detected by gene sequencing, or other confirmed RET translocations (e.g., CCDC6-RET).
3. Subjects may have received up to three prior systemic anticancer treatment regimens for adenocarcinoma of the lung (including adjuvant therapies and tyrosine-kinase inhibitors [TKI]), unless discussed with the sponsor.
4. Subjects must have a clinically indicated need for systemic chemotherapy for adenocarcinoma of the lung based on the investigator’s assessment.
5. Presence of measurable disease meeting the following criteria:
a. At least one lesion of at least 1.0 cm in the long-axis diameter for a non-lymph node or at least 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) using either
computerized tomography (CT) or magnetic resonance imaging (MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of at least 1.5 cm.
b. Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
6. Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection will be eligible if they have remained clinically stable, asymptomatic and off of steroids for 28 days.
7. Adequate bone marrow function.
8.Adequate liver function.
9.Adequate renal function, defined as calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula.
10.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1/Day 1 (C1D1).
11.Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) of 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 (Screen 1).
14.Females must not be breast-feeding 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.
17. Male subjects must have had a successful vasectomy y (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 (Screen 1 and Screen 2)
19. Willing and able to comply with all aspects of the protocol.
Exclusion Criteria
1. Subjects who have received any anticancer therapy (including surgery, locoregional, biological, immunotherapy, hormonal, or radiotherapy) within 21 days before the first dose of study drug (28 days for investigational therapies).
2. Leptomeningeal metastases or brain metastases except as for Inclusion Criterion #6.
3. Subjects who have not recovered from toxicities as a result of prior anticancer therapy to < Grade 2 severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0, except alopecia and infertility.
4. 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.
5. Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
6. Active malignancy (except for adenocarcinoma of the lung or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24months.
7. Major surgery within 3 weeks before the first dose of study drug.
8. Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring. (Treatment with low molecular weight heparin is allowed.)
9. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study drug.
10. Active infection (any infection requiring treatment).
11. Symptomatic central nervous system (CNS) disease.
12. Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24-hour will be ineligible.
13. Any medical or other condition that in the opinion of the investigator(s) would preclude the subject’s participation in a clinical study or would preclude them from completing the study.
14. Scheduled for surgery during the study.
2. Leptomeningeal metastases or brain metastases except as for Inclusion Criterion #6.
3. Subjects who have not recovered from toxicities as a result of prior anticancer therapy to < Grade 2 severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0, except alopecia and infertility.
4. 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.
5. Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
6. Active malignancy (except for adenocarcinoma of the lung or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24months.
7. Major surgery within 3 weeks before the first dose of study drug.
8. Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring. (Treatment with low molecular weight heparin is allowed.)
9. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study drug.
10. Active infection (any infection requiring treatment).
11. Symptomatic central nervous system (CNS) disease.
12. Subjects having > 1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24-hour will be ineligible.
13. Any medical or other condition that in the opinion of the investigator(s) would preclude the subject’s participation in a clinical study or would preclude them from completing the study.
14. Scheduled for surgery during the study.
The Estimated Number of Participants
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Taiwan
150 participants
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Global
1000 participants
