Advanced Solid TumorsPhase 1NCT02578316
A Study to Determine the Metabolism and Elimination of 14C-E7080 in Patients With Advanced Solid Tumors or Lymphomas, Who Are Unsuitable For, or Have Failed, Existing Therapies.
A Phase 1 study testing Lenvatinib in people with Advanced Solid Tumors and Lymphomas, run by Eisai Inc. at 1 site in Netherlands.
Trial summary
The purpose of this study was to determine the metabolism and elimination of 14C-lenvatinib in participants with advanced solid tumors or lymphomas, who were unsuitable for, or had failed, existing therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Lymphomas
- 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
- 6 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2009to Oct 2010
- Phase
- Phase 1
- 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
- Participants with histologically and/or cytologically confirmed solid tumor or lymphoma who were resistant/ refractory to approved therapies or for whom no appropriate therapies were available. Participants with measurable tumors according to RECIST were desirable but not essential for inclusion.
- All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicity must have resolved
- Aged greater than or equal to 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Could take oral study medication
- Gave written informed consent to participate in the study
- Willing and complied with the study protocol for the duration of the study.
Who cannot join
- Participants with brain or subdural metastases, unless they had completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs and/or symptoms of brain metastases those were stable for at least 4 weeks.
- Participants with meningeal carcinomatosis
- Any of the following values for laboratory parameters:
- hemoglobin less than 9 g/dL (5.6 mmol/L);
- neutrophils less than 1.5 x 10^9/L;
- platelets less than 100 x 10^9/L;
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- Prothrombin time (PT) [or International Normalized Ratio (INR)] and Patial thromboplastin time (PTT) > 1.5 x the upper limit of normal (ULN)
- serum bilirubin greater than 1.5 x ULN
- other liver parameters greater than 3 x ULN
- creatinine clearance less than 60 mL/min per the Cockcroft and Gault formula
- Uncontrolled infections
- Significant cardiovascular impairment (history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable ischemic heart disease including a myocardial infarction within six months of study start, or serious cardiac arrhythmia)
- Participants with marked baseline prolongation of QT/QT interval corrected for heart rate (QTc) interval (QTc interval greater than or equal to 500 msec) using the Fridericia method
- Any treatment with an investigational drug within the last 30 days
- Women who were pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at screening or no pregnancy test. Women of child-bearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator (including two forms of contraception, one of which must be a barrier method). Perimenopausal women who were amenorrheic for at least 12 months to be considered of non-child-bearing potential. Fertile males with female partners of child-bearing potential who were not willing to use contraception, or whose female partners were not using adequate contraceptive protection, were excluded.
- Proteinuria greater than 1+ on bedside testing
- History of gastrointestinal malabsorption
- Surgery within four weeks of start of study treatment
- Bleeding or thrombotic disorders or use of an anticoagulant, such as warfarin, with a therapeutic INR. Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), and low molecular weight heparin (LMWH) were permissible but when used with caution.
- Poorly controlled hypertension (defined as a change in hypertensive therapy within three months of study start) or participants diagnosed with hypertension (defined as a repeat blood pressure measurement of 160/90 mmHg or higher) at screening
- Previous lenvatinib therapy
- History of alcoholism, drug addiction, psychiatric or psychological condition, or social situation which, in the opinion of the investigator, would impair study compliance
- History of allergic reactions attributed to compounds of similar chemical or biological composition to lenvatinib
- Other significant disease or disorder that, in the Investigator's opinion, would exclude the participant from the study
- Legal incapacity
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Non-Randomized, Single-Center Study to Determine the Metabolism and Elimination of 14C-E7080 in Patients With Advanced Solid Tumors or Lymphomas, Who Are Unsuitable For, or Have Failed, Existing Therapies.
The purpose of this study was to determine the metabolism and elimination of 14C-lenvatinib in participants with advanced solid tumors or lymphomas, who were unsuitable for, or had failed, existing therapies.
Read the detailed description
The study comprised of two phases, the Study Phase and Extension Phase. Participants received 14C-lenvatinib on Day 1 of the Study Phase. Thereafter participants were given daily oral doses of 24 mg of lenvatinib over a 28 day cycle. During the Study Phase, participants received an initial single dose of 14C-lenvatinib oral patient dosing solution containing 24 mg of lenvatinib as anhydrous free base and radioactivity of 100 mCi (3.7 MBq) on Day 1, followed by collection of blood, urine and feces samples for pharmacokinetic analysis between Day 1 and Day 8, with a discharge visit on Day 8. Participants then entered the Extension Phase of the study to continue to receive once daily oral administration of non-radiolabeled lenvatinib at a dose of 24 mg. Each 28-day dosing period will be considered one treatment cycle.
- Conditions
- Advanced Solid Tumors, Lymphomas
- Being tested
- Lenvatinib
- Keywords
- Advanced Solid Tumors, Lymphomas
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080, Lenvima
Study phase dosing: participants received an initial single dose of radiolabelled 14C-lenvatinib oral patient dosing solution containing 24 mg of lenvatinib as anhydrous free base and radioactivity of 3.7 millibecquerel (MBq) on Day 1.
Extension phase dosing: 24 mg of 14C-lenvatinib: 2 x 10mg, and 4 x 1mg or 1 x 4mg tablets once-daily, continuously in each 28-day cycle during extension phase.
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib 24 mg | Experimental | Participants with advanced solid tumors or lymphomas, who are unsuitable for, or had failed, existing therapies. Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Individual blood/plasma concentration-time data were analyzed using 'non-compartmental' analysis. Cmax was determined from visual inspection of the individual blood/plasma concentration-time profile and was summarized as the Geometric Mean and percent coefficient of variation for the Geometric Mean (CV%) for all participants and expressed as nanograms/milliliter (ng/mL).
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Time of Maximum Plasma Concentration (Tmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Individual blood/plasma concentration-time data were analyzed using 'non-compartmental' analysis. Tmax was determined from visual inspection of the individual blood/plasma concentration-time profile and was summarized as the Geometric Mean (CV%) for all participants and expressed as hours.
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Terminal Phase Rate Constant (λz) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The terminal phase rate constant represents the rate at which study drug was eliminated from the body and was determined by log-linear regression of the plasma concentrations against time in the terminal phase and was summarized as the Geometric Mean (CV%) for all participants and expressed as 1/hours.
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Terminal Exponential Half-life (t1/2) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The terminal phase t1/2 is the time required to divide the plasma concentration of study drug by two after reaching pseudo-equilibrium, and not the time required to eliminate half of the administered dose of study drug. The t1/2 during the apparent terminal disposition phase was calculated at 0.693/λz and was summarized as the Geometric Mean (CV%) for all participants and expressed as hours.
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Area Under the Plasma Concentration-Time Curve From Time Zero to Time t (AUC(0-t))
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The AUC(0-t) was calculated by the combination of linear/log (from Tmax) trapezoidal rule where 't' is the time of last quantifiable plasma concentration following dosing. AUC(0-t) was summarized as the Geometric Mean (CV%) for all participants and expressed in nanograms·hour/milliliter (ng·hr/mL).
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC(0-inf))
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The AUC(0-inf) was calculated as AUC(0-t) + Ct/λz where Ct is the last measurable concentration and was summarized as the Geometric Mean (CV%) for all participants and expressed in ng·hr/mL.
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Percentage of Area Under the Plasma Concentration Curve Extrapolated to Infinity (%AUC(Extra))
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. %AUC(extra) was calculated as [(AUC(0-inf) - AUC(0-t)/AUC(0-inf) ]*100 and was summarized as the Geometric Mean (CV%) for all participants and expressed in (ng·hr/mL).
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Apparent Clearance (CL/F) of Lenvatinib From Plasma
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The CL/F for parent lenvatinib only was calculated as Dose/[AUC(0-inf)] and was summarized as the Geometric Mean (CV%) for all participants and expressed in L/hr.
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Apparent Terminal Volume of Distribution in the Terminal Phase of Lenvatinib (Vz/F)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Vz/F for lenvatinib only was calculated as Dose/[(λz)·(AUC(0-inf))] and was summarized as the Geometric Mean (CV%) for all participants and expressed in liters (L).
Measured: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Renal Clearance of Lenvatinib (CLr)
CLr was determined based on the interval amount and cumulative amount of the analyte excreted in the urine divided by its corresponding AUC over the same collection interval. Aeurine(0-t)/AUC(0-t), where t is the last measurable concentration, was calculated for lenvatinib only and was summarized as the Geometric Mean (CV%) for all participants and expressed in L/hr.
Measured: Pre-dose, post-dose at 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours
Percentage Recovery of 14^C- Lenvatinib Related Material in the Urine
Urine samples were collected at specific time points, then analyzed for the amount of 14^C- lenvatinib related material. The total radioactive dose of 14^C-lenvatinib excreted in urine (Aeurine%) was calculated from the time of dosing to the last quantifiable measurement. If radioactivity levels were still present at the end of the Study Phase, sampling continued until each sample contained less than 1% of the total radioactive dose. Percentage recovery of 14^C- lenvatinib related material in the urine was summarized as the Geometric Mean (CV%) percent cumulative for all participants and expressed as percent of 14^C- lenvatinib.
Measured: Pre-dose, post-dose at 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours
Percentage Recovery of 14^C- Lenvatinib Related Material in the Feces
Fecal samples were collected at specific time points, then analyzed for the amount of 14^C- lenvatinib related material. The percentage of the 14^C- lenvatinib dose excreted in feces (Aefeces%) was calculated from time of dosing to the last quantifiable measurement. If radioactivity levels were still present at the end of the Study Phase, sampling continued until each sample contained less than 1% of the total radioactive dose. Percentage recovery of 14^C- lenvatinib related material in the feces was summarized as the Geometric Mean (CV%) percent cumulative for all participants and expressed as percent of 14^C- lenvatinib.
Measured: Day 1 to Day 8
Secondary outcomes (2)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety was assessed by monitoring and recording all AEs including all Common Terminology Criteria for Adverse Events (CTCAE) grades (for both increasing and decreasing severity) and SAEs; regular monitoring of hematology, blood chemistry, and urine values; results of physical examinations, regular measurement of vital sign measurements, and 12-lead electrocardiogram (ECG), as detailed in the Schedule of Visits and Procedures. The relationship of AEs to treatment was based on investigator judgment. Details of AEs and SAEs are provided in the reported adverse event section.
Measured: Date of first dose of study treatment till 30 days after the last dose, assessed up to 1 year
Objective Tumor Response
A response of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) was assigned by the investigator as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. CR was defined as disappearance of all target lesions. Any pathological lymph node had to be reduced in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. PD was defined as a 20% or greater increase in the sum of the longest diameter of measured lesions, taking as reference the smallest sum longest diameter recorded since treatment start or the appearance of one or more new lesions. CR or PR was confirmed no less than 4 weeks after first observation of the response. For SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks. SD is defined as lasting at least 5 weeks.
Measured: Baseline to first date of documented CR, PR, SD, or PD, assessed up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2015 (estimated)
- Study startJun 2009
- Primary completionJun 2010
- Study completionOct 2010
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 (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 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
- NCT02578316
- Sponsor's protocol ID
- E7080-E044-104
- Status last verified
- Apr 2017
- First submitted
- 15 Oct 2015
- Last updated
- 20 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Dubbelman AC, Rosing H, Thijssen B, Gebretensae A, Lucas L, Chen H, Shumaker R, Schellens JH, Beijnen JH. Development and validation of LC-MS/MS assays for the quantification of E7080 and metabolites in various human biological matrices. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Mar 1;887-888:25-34. doi: 10.1016/j.jchromb.2012.01.004. Epub 2012 Jan 20.
PubMed 22309776
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Non-Randomized, Single-Center Study to Determine the Metabolism and Elimination of 14C-E7080 in Patients With Advanced Solid Tumors or Lymphomas, Who Are Unsuitable For, or Have Failed, Existing Therapies.
- ClinicalTrials.gov ID
- NCT02578316
- Acronym / sponsor ID
- E7080-E044-104
- Conditions
- Advanced Solid Tumors, Lymphomas
- Keywords
- Advanced Solid Tumors, Lymphomas
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Jun 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 16 Oct 2015 (estimated)
- Results
- Posted 20 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to determine the metabolism and elimination of 14C-lenvatinib in participants with advanced solid tumors or lymphomas, who were unsuitable for, or had failed, existing therapies.
Detailed description
The study comprised of two phases, the Study Phase and Extension Phase. Participants received 14C-lenvatinib on Day 1 of the Study Phase. Thereafter participants were given daily oral doses of 24 mg of lenvatinib over a 28 day cycle. During the Study Phase, participants received an initial single dose of 14C-lenvatinib oral patient dosing solution containing 24 mg of lenvatinib as anhydrous free base and radioactivity of 100 mCi (3.7 MBq) on Day 1, followed by collection of blood, urine and feces samples for pharmacokinetic analysis between Day 1 and Day 8, with a discharge visit on Day 8. Participants then entered the Extension Phase of the study to continue to receive once daily oral administration of non-radiolabeled lenvatinib at a dose of 24 mg. Each 28-day dosing period will be considered one treatment cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib 24 mg | Experimental | Drug: LenvatinibParticipants with advanced solid tumors or lymphomas, who are unsuitable for, or had failed, existing therapies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participants with histologically and/or cytologically confirmed solid tumor or lymphoma who were resistant/ refractory to approved therapies or for whom no appropriate therapies were available. Participants with measurable tumors according to RECIST were desirable but not essential for inclusion.
- All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicity must have resolved
- Aged greater than or equal to 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Could take oral study medication
Key exclusion criteria (25 listed)
- Participants with brain or subdural metastases, unless they had completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs and/or symptoms of brain metastases those were stable for at least 4 weeks.
- Participants with meningeal carcinomatosis
- Any of the following values for laboratory parameters:
- Uncontrolled infections
- Significant cardiovascular impairment (history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable ischemic heart disease including a myocardial infarction within six months of study start, or serious cardiac arrhythmia)
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: E7080, LenvimaStudy phase dosing: participants received an initial single dose of radiolabelled 14C-lenvatinib oral patient dosing solution containing 24 mg of lenvatinib as anhydrous free base and radioactivity of 3.7 millibecquerel (MBq) on Day 1. Extension phase dosing: 24 mg of 14C-lenvatinib: 2 x 10mg, and 4 x 1mg or 1 x 4mg tablets once-daily, continuously in each 28-day cycle during extension phase. | Drug | Lenvatinib 24 mg |
Primary outcome
Maximum Plasma Concentration (Cmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Individual blood/plasma concentration-time data were analyzed using 'non-compartmental' analysis. Cmax was determined from visual inspection of the individual blood/plasma concentration-time profile and was summarized as the Geometric Mean and percent coefficient of variation for the Geometric Mean (CV%) for all participants and expressed as nanograms/milliliter (ng/mL).
Time of Maximum Plasma Concentration (Tmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Individual blood/plasma concentration-time data were analyzed using 'non-compartmental' analysis. Tmax was determined from visual inspection of the individual blood/plasma concentration-time profile and was summarized as the Geometric Mean (CV%) for all participants and expressed as hours.
Terminal Phase Rate Constant (λz) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The terminal phase rate constant represents the rate at which study drug was eliminated from the body and was determined by log-linear regression of the plasma concentrations against time in the terminal phase and was summarized as the Geometric Mean (CV%) for all participants and expressed as 1/hours.
Terminal Exponential Half-life (t1/2) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The terminal phase t1/2 is the time required to divide the plasma concentration of study drug by two after reaching pseudo-equilibrium, and not the time required to eliminate half of the administered dose of study drug. The t1/2 during the apparent terminal disposition phase was calculated at 0.693/λz and was summarized as the Geometric Mean (CV%) for all participants and expressed as hours.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time t (AUC(0-t))
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The AUC(0-t) was calculated by the combination of linear/log (from Tmax) trapezoidal rule where 't' is the time of last quantifiable plasma concentration following dosing. AUC(0-t) was summarized as the Geometric Mean (CV%) for all participants and expressed in nanograms·hour/milliliter (ng·hr/mL).
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC(0-inf))
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The AUC(0-inf) was calculated as AUC(0-t) + Ct/λz where Ct is the last measurable concentration and was summarized as the Geometric Mean (CV%) for all participants and expressed in ng·hr/mL.
Percentage of Area Under the Plasma Concentration Curve Extrapolated to Infinity (%AUC(Extra))
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. %AUC(extra) was calculated as [(AUC(0-inf) - AUC(0-t)/AUC(0-inf) ]*100 and was summarized as the Geometric Mean (CV%) for all participants and expressed in (ng·hr/mL).
Apparent Clearance (CL/F) of Lenvatinib From Plasma
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The CL/F for parent lenvatinib only was calculated as Dose/[AUC(0-inf)] and was summarized as the Geometric Mean (CV%) for all participants and expressed in L/hr.
Apparent Terminal Volume of Distribution in the Terminal Phase of Lenvatinib (Vz/F)
Time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)
Blood samples were drawn at specific time points then analyzed for the amount of 14^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Vz/F for lenvatinib only was calculated as Dose/[(λz)·(AUC(0-inf))] and was summarized as the Geometric Mean (CV%) for all participants and expressed in liters (L).
Renal Clearance of Lenvatinib (CLr)
Time frame: Pre-dose, post-dose at 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours
CLr was determined based on the interval amount and cumulative amount of the analyte excreted in the urine divided by its corresponding AUC over the same collection interval. Aeurine(0-t)/AUC(0-t), where t is the last measurable concentration, was calculated for lenvatinib only and was summarized as the Geometric Mean (CV%) for all participants and expressed in L/hr.
Percentage Recovery of 14^C- Lenvatinib Related Material in the Urine
Time frame: Pre-dose, post-dose at 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours
Urine samples were collected at specific time points, then analyzed for the amount of 14^C- lenvatinib related material. The total radioactive dose of 14^C-lenvatinib excreted in urine (Aeurine%) was calculated from the time of dosing to the last quantifiable measurement. If radioactivity levels were still present at the end of the Study Phase, sampling continued until each sample contained less than 1% of the total radioactive dose. Percentage recovery of 14^C- lenvatinib related material in the urine was summarized as the Geometric Mean (CV%) percent cumulative for all participants and expressed as percent of 14^C- lenvatinib.
Percentage Recovery of 14^C- Lenvatinib Related Material in the Feces
Time frame: Day 1 to Day 8
Fecal samples were collected at specific time points, then analyzed for the amount of 14^C- lenvatinib related material. The percentage of the 14^C- lenvatinib dose excreted in feces (Aefeces%) was calculated from time of dosing to the last quantifiable measurement. If radioactivity levels were still present at the end of the Study Phase, sampling continued until each sample contained less than 1% of the total radioactive dose. Percentage recovery of 14^C- lenvatinib related material in the feces was summarized as the Geometric Mean (CV%) percent cumulative for all participants and expressed as percent of 14^C- lenvatinib.
2 secondary outcomes
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Date of first dose of study treatment till 30 days after the last dose, assessed up to 1 year
Objective Tumor Response
Time frame: Baseline to first date of documented CR, PR, SD, or PD, assessed up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22309776Dubbelman AC, Rosing H, Thijssen B, Gebretensae A, Lucas L, Chen H, Shumaker R, Schellens JH, Beijnen JH. Development and validation of LC-MS/MS assays for the quantification of E7080 and metabolites in various human biological matrices. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Mar 1;887-888:25-34. doi: 10.1016/j.jchromb.2012.01.004. Epub 2012 Jan 20.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenvatinib in people with Advanced Solid Tumors and Lymphomas, run by Eisai Inc. at 1 site in Netherlands.
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 7 inclusion and 25 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 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 20 Jun 2017). 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?
Maximum Plasma Concentration (Cmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib (time frame: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)). The study lists 12 primary outcomes in all. 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 NCT02578316, which also lists 1 linked publication.
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 20 Jun 2017.