Trial Outcomes & Findings for 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. (NCT NCT02578316)

Last Updated: 2017-06-20

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

6 participants

Primary outcome timeframe

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)

Results posted on

2017-06-20

Participant Flow

Participant milestones

Participant milestones
Measure	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity
Study Phase STARTED	6
Study Phase COMPLETED	6
Study Phase NOT COMPLETED	0
Extension Phase STARTED	6
Extension Phase COMPLETED	0
Extension Phase NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity
Extension Phase Progression of disease	6

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Age, Continuous	48.8 Years STANDARD_DEVIATION 12.62 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

Population: The Pharmacokinetic (PK) Analysis Set is the group of participants who received the Study Phase dose of 14\^C-lenvatinib and have any evaluable post 14\^C- lenvatinib dose plasma and/or blood concentration data.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Maximum Plasma Concentration (Cmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib	485.2 ng/mL Geometric Coefficient of Variation 37.08	426.8 ng/mL Geometric Coefficient of Variation 46.59

PRIMARY outcome

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Time of Maximum Plasma Concentration (Tmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib	1.418 Hours Geometric Coefficient of Variation 41.95	1.604 Hours Geometric Coefficient of Variation 39.33

PRIMARY outcome

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Terminal Phase Rate Constant (λz) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma	0.039 1/hour Geometric Coefficient of Variation 39.5787	0.020 1/hour Geometric Coefficient of Variation 24.7258

PRIMARY outcome

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Terminal Exponential Half-life (t1/2) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma	17.78 Hours Geometric Coefficient of Variation 39.44	34.54 Hours Geometric Coefficient of Variation 25.12

PRIMARY outcome

Population: PK Analysis Set

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).

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time t (AUC(0-t))	5223 ng·hr/mL Geometric Coefficient of Variation 55.00	3440 ng·hr/mL Geometric Coefficient of Variation 49.72

PRIMARY outcome

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC(0-inf))	5783 ng·hr/mL Geometric Coefficient of Variation 48.22	3469 ng·hr/mL Geometric Coefficient of Variation 49.95

PRIMARY outcome

Population: PK Analysis Set

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).

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Percentage of Area Under the Plasma Concentration Curve Extrapolated to Infinity (%AUC(Extra))	8.637 Percent lenvatinib Geometric Coefficient of Variation 46.9657	0.786 Percent lenvatinib Geometric Coefficient of Variation 44.2610

PRIMARY outcome

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Apparent Clearance (CL/F) of Lenvatinib From Plasma	6.739 L/hour Geometric Coefficient of Variation 49.54	—

PRIMARY outcome

Population: PK Analysis Set

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).

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Apparent Terminal Volume of Distribution in the Terminal Phase of Lenvatinib (Vz/F)	335.7 L Geometric Coefficient of Variation 36.69	—

PRIMARY outcome

Timeframe: 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

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Renal Clearance of Lenvatinib (CLr)	0.042 L/hour Geometric Coefficient of Variation 140.3	—

PRIMARY outcome

Timeframe: 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

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Percentage Recovery of 14^C- Lenvatinib Related Material in the Urine	24.74 Percentage of 14^C-lenvatinib Geometric Coefficient of Variation 17.76	—

PRIMARY outcome

Timeframe: Day 1 to Day 8

Population: PK Analysis Set

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Percentage Recovery of 14^C- Lenvatinib Related Material in the Feces	63.56 Percentage of 14^C-lenvatinib Geometric Coefficient of Variation 11.24	—

SECONDARY outcome

Timeframe: Date of first dose of study treatment till 30 days after the last dose, assessed up to 1 year

Population: The Safety Analysis Set was the group of participants who received at least one partial dose of study drug and had at least one postdose safety assessment.

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any TEAEs	100 Percentage of participants	—
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment-related TEAEs	100 Percentage of participants	—
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious TEAEs	50.0 Percentage of participants	—
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) TEAEs requiring study drug reduction	33.3 Percentage of participants	—
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) TEAEs requiring dose interruption	83.3 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline to first date of documented CR, PR, SD, or PD, assessed up to 1 year

Population: The Response Evaluable Population is the group of participants who received at least a partial dose of study treatment who had measureable disease per RECIST at baseline.

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.

Outcome measures

Outcome measures
Measure	14^C-Lenvatinib n=6 Participants Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for PK analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.	Lenvatinib Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity.
Objective Tumor Response Complete response	0 Percentage of participants	—
Objective Tumor Response Partial Response	16.7 Percentage of participants	—
Objective Tumor Response Stable disease	50.0 Percentage of participants	—
Objective Tumor Response Progressive disease	33.3 Percentage of participants	—

Adverse Events

Lenvatinib

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lenvatinib n=6 participants at risk Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity
Gastrointestinal disorders Ileus	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Nausea	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
General disorders Disease progression	33.3% 2/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Metabolism and nutrition disorders Hyponatraemia	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.

Other adverse events

Other adverse events
Measure	Lenvatinib n=6 participants at risk Study Phase: Participants received a single dose of an oral dosing solution of 14\^C-labeled lenvatinib (approximately 100 μCi or 3.7 MBq) and approximately 24 mg non-radiolabeled lenvatinib on Day 1. From Days 1 to 8, participants remained in the research unit so blood, urine, and fecal samples could be collected for pharmacokinetic (PK) analysis and determination of 14\^C-lenvatinib concentrations prior to, and for 7 days following, drug administration. Participants were discharged after the checkout procedures were completed on Day 8, or when the level of radiation in urine and fecal samples was less than 1% of the total radioactive dose. Extension Phase: Participants received 24 mg oral lenvatinib once daily at home or at the clinic on Visit Days 1, 8, 15, and 22 of each treatment cycle (1 treatment cycle = 28 days) until discontinuation from the study. The dose of lenvatinib could be reduced or discontinued during any cycle because of toxicity
Blood and lymphatic system disorders Thrombocytopenia	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Abdominal pain upper	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Constipation	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Diarrhoea	66.7% 4/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Glossodynia	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Ileus	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Nausea	50.0% 3/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Oral pain	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Proctalgia	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Rectal haemorrhage	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Stomatitis	66.7% 4/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Gastrointestinal disorders Vomiting	50.0% 3/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
General disorders Disease progression	33.3% 2/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
General disorders Fatigue	66.7% 4/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
General disorders Feeling cold	33.3% 2/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
General disorders Oedema peripheral	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Hepatobiliary disorders Hepatic function abnormal	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Infections and infestations Cystitis	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Infections and infestations Oral candidiasis	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Infections and infestations Urinary tract infection	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Investigations Blood pressure increased	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Investigations Weight decreased	50.0% 3/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Metabolism and nutrition disorders Hyponatraemia	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Musculoskeletal and connective tissue disorders Back pain	33.3% 2/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Musculoskeletal and connective tissue disorders Bone pain	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 2/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Nervous system disorders Neuropathy peripheral	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Psychiatric disorders Insomnia	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Renal and urinary disorders Proteinuria	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Respiratory, thoracic and mediastinal disorders Dysphonia	66.7% 4/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Skin and subcutaneous tissue disorders Blister	33.3% 2/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Skin and subcutaneous tissue disorders Dry skin	50.0% 3/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.
Vascular disorders Hypertension	16.7% 1/6 • Approximately 17 months. Treatment-emergent adverse events (TEAEs) were defined as any event with start date/time beyond or equal to the day of initial dosing, and/or any adverse event (AE) for which an increase in severity occurs during the trial. All AEs were graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.

Additional Information

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Eisai Inc.

Phone: 888-

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Principal investigator is a sponsor employee
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