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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01136967
Registration number
NCT01136967
Ethics application status
Date submitted
2/06/2010
Date registered
4/06/2010
Date last updated
13/11/2019
Titles & IDs
Public title
An Open-Label, 2-Cohort, Multicenter, Study of Lenvatinib in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma
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Scientific title
An Open-Label, 2-Cohort, Multicenter, Phase 2 Study of E7080 (Lenvatinib) in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma
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Secondary ID [1]
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E7080-G000-206
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Unresectable Stage III
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Stage IV Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Lenvatinib
Experimental: Cohort 1 (V600E BRAF negative) - Cohort 1 (V600E BRAF negative) enrolled participants not harboring the V600E BRAF mutation with disease progression following up to 2 prior systemic anticancer regimens (excluding anti-VEGF) for unresectable Stage III or Stage IV melanoma.
Experimental: Cohort 2 (V600E BRAF positive) - Cohort 2 (V600E BRAF positive) enrolled participants harboring the activating BRAF mutations (mainly the V600E mutation) with disease progression following BRAF V600E-targeted therapy.
Treatment: Drugs: Lenvatinib
Participants received lenvatinib 24 mg orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Objective Response Rate (ORR)
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Assessment method [1]
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ORR, (ORR = CR + PR) was defined as the percentage of participants in each cohort who had a best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 for target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans and independent radiologic review (IRR). A BOR of CR required confirmation by a subsequent CR assessment at least 4 weeks later. A BOR of PR required confirmation by a subsequent assessment of CR or PR at least 4 weeks later. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have a reduction in short axis to less than (<)10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Timepoint [1]
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From date of treatment start until all participants completed a minimum of 6 cycles (28-day cycles) or discontinued treatment prior to end of Cycle 6 (up to 24 weeks)
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Secondary outcome [1]
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Progression Free Survival (PFS)
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Assessment method [1]
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PFS was measured as the time from the date of first administration of study treatment until the date of first documentation of disease progression or date of death from any cause (whichever occurred first), as determined by IRR and Investigator based on RECIST v1.1. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was analyzed using Kaplan-Meier (1958) product-limit estimates. Data were presented with 2-sided 95% confidence interval (CI) when an adequate number of at risk participants warranted the estimates in the table below.
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Timepoint [1]
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From date of treatment start until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months
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Secondary outcome [2]
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Overall Survival (OS)
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Assessment method [2]
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OS was defined as the length of time in months from the date of first administration of study drug until the date of death from any cause, and was based on the data cutoff date for each cohort. OS was analyzed using Kaplan-Meier (1958) product-limit estimates. Data were presented with 2-sided 95% CI when an adequate number of at risk participants warranted the estimates in the table below.
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Timepoint [2]
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From date of treatment start until date of death from any cause or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months
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Secondary outcome [3]
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Disease Control Rate (DCR)
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Assessment method [3]
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DCR, (DCR = CR + PR + SD) was defined as the percentage of participants who had a BOR of CR or PR or stable disease (SD) based on RECIST v1.1 for target lesions assessed by MRI/CT and IRR. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (target or non-target) had to have a reduction in short axis to <10 mm.; PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Overall Response (OR) = CR + PR. SD defined as reduction in tumor volume of < 30% or an increase in the volume of 1 or more measurable lesions of < 25% without the appearance of any new lesions which was neither tumor shrinkage corresponding to PR nor tumor expansion corresponding to disease progression. BOR of SD, time from first administration of study drug until date of documented SD needed to be >=7 weeks based on IRR and Investigator's assessment.
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Timepoint [3]
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From date of treatment start until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months
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Secondary outcome [4]
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Clinical Benefit Rate (CBR)
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Assessment method [4]
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CBR, (CBR = CR + PR + durable SD rate) was defined as the percentage of participants who had a BOR of CR or PR or durable SD (dSD, SD lasting >=23 weeks) based on RECIST v1.1 for target lesions assessed by MRI/CT, IRR and Investigator's assessment. A BOR of CR required confirmation by a subsequent CR assessment at least 4 weeks later. A BOR of PR required confirmation by a subsequent assessment of CR or PR at least 4 weeks later. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (target or non-target) had to have a reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; OR = CR + PR. A BOR of dSD, the time from the first administration of study drug until the date of documented dSD needed to be =23 weeks based on IRR and Investigator's assessment.
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Timepoint [4]
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From date of treatment start until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months
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Secondary outcome [5]
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Number of Participants With Adverse Events (AEs)/ Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
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Assessment method [5]
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Safety was assessed by monitoring and recording all AEs including all Common Terminology Criteria for Adverse Events (CTCAE) grades and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, electrocardiograms (ECGs), and multi-gated acquisition (MUGA) scans or echocardiogram.
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Timepoint [5]
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From date of treatment start up to 30 days after the last dose, or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 9 months
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Secondary outcome [6]
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Change From Baseline in the Concentration of Clinical Biomarkers in Whole Blood
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Assessment method [6]
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Blood samples were drawn at specific time points. Utilizing a standard protocol, the deoxyribonucleic acid (DNA) from whole blood was extracted and analyzed for specific biomarkers of absorption, distribution, metabolism, and excretion of lenvatinib. Some of the biomarkers analyzed included; Angiopoietin, Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), FMS Like Tyrosine Kinase 3 Ligand (Flt3l) Granulocyte Colony Stimulating Factor (G-CSF), Granulocyte Macro Colony Stimulating Factor (GM-CSF), Interleukin 1 Receptor Antagonist (IL-1RA), Interferon (IFN), Macrophage Inflammatory Protein (MIP) 1 alpha, Platelet Derived Growth Factor (PDGF), Stromal Cell Derived Factor (SDF) 1 alpha, Interleukin (IL), Transforming Growth Factor (TGF), Tumor Necrosis Factor (TNF), Vascular Endothelial Growth Factor (VEGF).
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Timepoint [6]
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Cycle 1 Day 15 (C1 D15), Cycle 2 Day 1 (C2 D1), Cycle 3 Day 1 (C3 D1), Off-Treatment/Phase Visit 98 (V98)
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Secondary outcome [7]
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Summary of Plasma Concentration of Lenvatinib
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Assessment method [7]
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Blood samples for the quantification of lenvatinib in plasma were obtained and processed using a standardized protocol. The lower limit of quantification was 0.25 ng/mL. Pharmacokinetic (PK) analysis was conducted using nonlinear mixed effects modeling. Descriptive statistics were used to summarize lenvatinib plasma concentration data.
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Timepoint [7]
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Predose and 2 to 12 hours postdose at Cycle 1 Day 1 (C1D1), Cycle 1 Day 15 (C1D15), and Cycle 2 Day 1 (C2D1)
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Eligibility
Key inclusion criteria
1. Histologically confirmed diagnosis of melanoma.
2. Unresectable Stage III or Stage IV melanoma.
3. Evidence of disease progression according to RECIST 1.1 on prior regimen.
4. Participants with brain metastases will be eligible if they have undergone complete
surgical excision and are more then 1 month post surgery with no radiographic evidence
of disease recurrence in the brain or have undergone stereotactic radio surgery (gamma
knife procedure) and are more then 1 month post procedure and with no radiographic
evidence of disease progression in the brain; and are asymptomatic, and discontinued
corticosteroid treatment at least 30 days prior starting treatment.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Adequately controlled blood pressure.
7. Adequate renal function, bone marrow function, blood coagulation function, and liver
function, as defined in the study protocol.
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Minimum age
18
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Maximum age
99
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Melanoma of intraocular origin.
2. Leptomeningeal metastases or brain metastases except as for participants with brain
metastases will be eligible if they have undergone complete surgical excision and are
more then 1 month post surgery with no radiographic evidence of disease recurrence in
the brain or have undergone stereotactic radio surgery (gamma knife procedure) and are
more then 1 month post procedure and with no radiographic evidence of disease
progression in the brain; and are asymptomatic, and discontinued corticosteroid
treatment at least 30 days prior starting treatment.
3. More than 2 prior systemic anticancer regimen treatments including immunotherapies for
unresectable Stage III or Stage IV disease (if BRAF V600E mutation negative) or not
previously treated with BRAF V600E-targeted therapy or received in the past more than
2 prior systemic anticancer regimen treatments, including immunotherapies, in addition
to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive).
4. Significant cardiovascular impairment.
5. Bleeding disorder or a thrombotic disorder requiring anticoagulant therapy.
6. Females who are pregnant or breastfeeding.
7. Prolongation of QTc interval to greater than 480 msec.
8. 24 hour urine protein greater than or equal to 1 gm.
9. Active hemoptysis within 3 wks prior to the first dose of study drug.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/08/2010
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/11/2014
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Sample size
Target
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Accrual to date
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Final
182
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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- Adelaide
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- Malvern
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- Newcastle
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- North Sydney
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- Perth
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Recruitment hospital [6]
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- Westmead
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Recruitment postcode(s) [1]
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- Adelaide
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Recruitment postcode(s) [2]
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- Malvern
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Recruitment postcode(s) [3]
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- Newcastle
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- North Sydney
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- Perth
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Recruitment postcode(s) [6]
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- Westmead
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Recruitment outside Australia
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United States of America
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Alabama
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Essen
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Hannover
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Heidelberg
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Kiel
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Mainz
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Tubingen
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Eisai Inc.
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Ethics approval
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Summary
Brief summary
The purpose of this study is to assess the objective response rate of lenvatinib in
previously treated participants with American Joint Committee on Cancer (AJCC) unresectable
Stage III or Stage IV melanoma and disease progression.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01136967
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Eisai US Medical Services
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Address
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Eisai Limited
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01136967
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