KIF5B-RET-Positive Adenocarcinoma of the LungPhase 2NCT01877083
Study of the Safety and Activity of Lenvatinib (E7080) in Subjects With KIF5B-RET-Positive Adenocarcinoma of the Lung
A Phase 2 study testing Lenvatinib in people with KIF5B-RET-Positive Adenocarcinoma of the Lung, run by Eisai Inc. at 23 sites in 5 countries.
Trial summary
This is a Phase 2, open-label, safety and activity study of lenvatinib in subjects with KIF5B-RET-positive adenocarcinoma of the lung and other confirmed RET translocations. At least 20 subjects with KIF5B-RET and other RET translocations will be treated and will receive lenvatinib at a starting dose of 24 mg orally… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- KIF5B-RET-Positive Adenocarcinoma of the Lung
- What is being tested?
- Lenvatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 23 sitesin 5 countries
- Study dates
- 5 Apr 2013to 2 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have a cytological or histological confirmed diagnosis of adenocarcinoma of the lung.
- Subject must be known to be RET positive (known KIF5B-RET translocation, or other confirmed RET translocations (e.g., CCDC6-RET)) or have an available tumor sample for local or central testing obtained prior to consent (Screen 1). Subjects whose samples need to be submitted for central laboratory testing must be current non-smokers and not known to have mutation in EGFR, KRAS, or ALK.
- 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.
- Subjects must have a clinically indicated need for systemic chemotherapy for adenocarcinoma of the lung based on the investigator's assessment
- Presence of measurable disease meeting the following criteria:
- 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.
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- Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
- 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.
- Adequate bone marrow function, defined as:
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L (greater than or equal to 1500/mm^3)
- Hemoglobin (Hb) greater than or equal 8.5 g/dL
- Platelet count greater than or equal 75 x 10^9/L (greater than or equal 75,000/mm^3)
- Adequate liver function, defined as:
- Bilirubin less than or equal 1.5 x upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) less than or equal 3 x ULN (less than or equal 5 x ULN if subject has liver metastases). If alkaline phosphatase is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND the subject also is known to have bone metastases, the liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of total alkaline phosphatase.
- Adequate renal function, defined as calculated creatinine clearance greater than 40 mL/min per the Cockcroft and Gault formula.
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1/Day 1 (C1D1).
- Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) of 0 or 1.
- Survival expectation of 12 weeks or longer after starting study drug.
- 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).
- Females must not be breast-feeding or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of B-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.
- 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).
- 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.
- 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.
- Provide written informed consent (Screen 1 and Screen 2)
- Willing and able to comply with all aspects of the protocol
Who cannot join
- 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).
- Leptomeningeal metastases or brain metastases except as for Inclusion Criterion #6.
- Subjects who have not recovered from toxicities as a result of prior anticancer therapy to less than Grade 2 severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0, except alopecia and infertility.
- 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.
- Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
- 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.
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- Major surgery within 3 weeks before the first dose of study drug.
- 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.)
- Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study drug.
- Active infection (any infection requiring treatment).
- Symptomatic central nervous system (CNS) disease.
- Subjects having greater than 1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein greater than or equal to 1 g/24-hour will be ineligible.
- 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.
- Scheduled for surgery during the study.
Trial locations and contacts
23 sites in 5 countries.
23 sites in 5 countries
Japan9 sites
Study site
Akashi, Hyōgo
Study site
Chuo-ku, Tokyo
Study site
Fukuoka
Study site
Kashiwa, Chiba
Study site
Kobe, Hyōgo
Study site
Koto-Ku, Tokyo
Study site
Nagoya, Aichi-ken
Study site
Natori-shi, Miyagi
Study site
Ōsaka-sayama, Osaka
United States8 sites
Study site
Canton, Ohio
Study site
Cleveland, Ohio
Study site
Dallas, Texas
Study site
Duarte, California
Study site
Jacksonville, Florida
Study site
Knoxville, Tennessee
Study site
La Jolla, California
Study site
Whittier, California
Singapore2 sites
National Cancer Center Hospital
Singapore
National University Hospital
Singapore
Taiwan2 sites
National Taiwan University Hospital
Taipei
Veterans General Hospital Taipei
Taipei
About this study
Official title: 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
This is a Phase 2, open-label, safety and activity study of lenvatinib in subjects with KIF5B-RET-positive adenocarcinoma of the lung and other confirmed RET translocations. At least 20 subjects with KIF5B-RET and other RET translocations will be treated and will receive lenvatinib at a starting dose of 24 mg orally, once per day. The study will consist of 3 phases: The Pretreatment Phase, The Treatment Phase and the Extension Phase. The Pretreatment Phase will include screening procedures and eligibility assessments. The Pretreatment Phase consists of a Screen 1, Screen 2 and Baseline Period. The Treatment Phase will begin when the subject has met all eligibility criteria on Day 1 of the first Treatment Cycle. The Treatment Phase contains the Treatment and Follow-up Periods. The Extension Phase will begin for subjects who received treatment in the study (either in the Treatment Period or Follow-up Period) at the time of database cutoff.
- Being tested
- Lenvatinib
- Keywords
- KIF5B-RET-Positive Adenocarcinoma, Lung Cancer, NSCLC, Non-Small Cell Lung Cancer
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080
Starting dose of 24 mg orally, once per day
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib | Experimental | Not described Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the investigator assessment of radiologic response according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. No independent review of tumor assessments was performed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: From first dose date until PD, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment (up to approximately 2 years 10 months)
Secondary outcomes (3)
Progression-free Survival (PFS)
PFS was defined as the time from the first dose to the date of first documentation of PD, or date of death, whichever occurred first. Tumor response data used to analyze PFS was obtained from the investigator's assessment of the imaging scans using RECIST 1.1. No independent review of tumor assessments were performed. PFS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% Cl based on the Greenwood formula. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions.
Measured: From first dose date until PD or death (up to approximately 2 years 10 months)
Overall Survival (OS)
OS was defined as the time from the date of first dose to the date of death from any cause. OS was calculated using Kaplan-Meier estimate and presented with 2-sided 95% Cl based on the Greenwood formula.
Measured: From first dose date until date of death from any cause (approximately up to 2 years 10 months)
Plasma Concentrations of Lenvatinib
Measured: Cycle 1 Day 1: 0.5-4 hours, 6-10 hours postdose; Cycle 1 Day 15: predose, 0.5-4 hours, 6-10 hours postdose; Cycle 2 Day 1: predose, 2-12 hours postdose; Cycle 3 Day 1: predose; (Cycle length is equal to [=] 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2013 (estimated)
- Study start5 Apr 2013
- Primary completion3 Feb 2016
- Study completion2 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for KIF5B-RET-Positive Adenocarcinoma of the LungStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01877083
- Sponsor's protocol ID
- E7080-G000-209
- Status last verified
- Jan 2018
- First submitted
- 11 Jun 2013
- Last updated
- 13 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer. 2019 Dec;138:124-130. doi: 10.1016/j.lungcan.2019.09.011. Epub 2019 Sep 16.
PubMed 31710864Wu H, Shih JY, Yang JC. Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B-RET Fusion Gene. J Thorac Oncol. 2015 Sep;10(9):e95-e96. doi: 10.1097/JTO.0000000000000611. No abstract available.
PubMed 26291023
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01877083
- Acronym / sponsor ID
- E7080-G000-209
- Keywords
- KIF5B-RET-Positive Adenocarcinoma, Lung Cancer, NSCLC, Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Apr 2013 (actual)
- Primary completion
- 3 Feb 2016 (actual)
- Study completion
- 2 Nov 2017 (actual)
- First posted
- 13 Jun 2013 (estimated)
- Results
- Posted 13 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, open-label, safety and activity study of lenvatinib in subjects with KIF5B-RET-positive adenocarcinoma of the lung and other confirmed RET translocations. At least 20 subjects with KIF5B-RET and other RET translocations will be treated and will receive lenvatinib at a starting dose of 24 mg orally, once per day. The study will consist of 3 phases: The Pretreatment Phase, The Treatment Phase and the Extension Phase. The Pretreatment Phase will include screening procedures and eligibility assessments. The Pretreatment Phase consists of a Screen 1, Screen 2 and Baseline Period. The Treatment Phase will begin when the subject has met all eligibility criteria on Day 1 of the first Treatment Cycle. The Treatment Phase contains the Treatment and Follow-up Periods. The Extension Phase will begin for subjects who received treatment in the study (either in the Treatment Period or Follow-up Period) at the time of database cutoff.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib | Experimental | Drug: Lenvatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Subjects must have a cytological or histological confirmed diagnosis of adenocarcinoma of the lung.
- Subject must be known to be RET positive (known KIF5B-RET translocation, or other confirmed RET translocations (e.g., CCDC6-RET)) or have an available tumor sample for local or central testing obtained prior to consent (Screen 1). Subjects whose samples need to be submitted for central laboratory testing must be current non-smokers and not known to have mutation in EGFR, KRAS, or ALK.
- 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.
- Subjects must have a clinically indicated need for systemic chemotherapy for adenocarcinoma of the lung based on the investigator's assessment
- Presence of measurable disease meeting the following criteria:
Key exclusion criteria (14 listed)
- 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).
- Leptomeningeal metastases or brain metastases except as for Inclusion Criterion #6.
- Subjects who have not recovered from toxicities as a result of prior anticancer therapy to less than Grade 2 severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0, except alopecia and infertility.
- 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.
- Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: E7080Starting dose of 24 mg orally, once per day | Drug | Lenvatinib |
Primary outcome
Objective Response Rate (ORR)
Time frame: From first dose date until PD, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment (up to approximately 2 years 10 months)
ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the investigator assessment of radiologic response according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. No independent review of tumor assessments was performed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters.
3 secondary outcomes
Progression-free Survival (PFS)
Time frame: From first dose date until PD or death (up to approximately 2 years 10 months)
Overall Survival (OS)
Time frame: From first dose date until date of death from any cause (approximately up to 2 years 10 months)
Plasma Concentrations of Lenvatinib
Time frame: Cycle 1 Day 1: 0.5-4 hours, 6-10 hours postdose; Cycle 1 Day 15: predose, 0.5-4 hours, 6-10 hours postdose; Cycle 2 Day 1: predose, 2-12 hours postdose; Cycle 3 Day 1: predose; (Cycle length is equal to [=] 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31710864Hida T, Velcheti V, Reckamp KL, Nokihara H, Sachdev P, Kubota T, Nakada T, Dutcus CE, Ren M, Tamura T. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer. 2019 Dec;138:124-130. doi: 10.1016/j.lungcan.2019.09.011. Epub 2019 Sep 16.
- Derived from this study: PubMed 26291023Wu H, Shih JY, Yang JC. Rapid Response to Sunitinib in a Patient with Lung Adenocarcinoma Harboring KIF5B-RET Fusion Gene. J Thorac Oncol. 2015 Sep;10(9):e95-e96. doi: 10.1097/JTO.0000000000000611. No abstract available.
Related trials for KIF5B-RET-Positive Adenocarcinoma of the Lung
Active, not recruitingPhase 1/2
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
Non-Small Cell Lung Cancer, Medullary Thyroid Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenvatinib in people with KIF5B-RET-Positive Adenocarcinoma of the Lung, run by Eisai Inc. at 23 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Japan, United States, Hong Kong, Singapore, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: From first dose date until PD, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment (up to approximately 2 years 10 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01877083, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2019.