A Phase 1/2 interventional study of Lenvatinib and Lenvatinib in Tumors, Solid Malignant Tumors and Osteosarcoma, sponsored by Eisai Limited. Completed at 19 sites in 6 countries. Open to participants aged 2 Years to 25 Years. Per ClinicalTrials.gov, last updated 2023-07-11.
Sponsored by Eisai Limited · Phase 1/2, Interventional, and Treatment
This is a phase 1/2 study evaluating safety, tolerability, and efficacy of lenvatinib as single-agent, and in combination with chemotherapy (ifosfamide and etoposide) in children and adolescents with refractory or relapsed solid malignancies including differentiated thyroid carcinoma (single agent lenvatinib) and osteosarcoma (single agent and combination lenvatinib).
The study consists of 5 cohorts:
Cohort 1 (Single-Agent Dose-Finding) dose-escalation to find the recommended dose (RD) of lenvatinib using time-to-event continual reassessment method (TiTE-CRM) in children and adolescents with relapsed or refractory solid malignant tumors. When the RD is identified, Cohorts 2A, 2B, and 3A will enroll in parallel.
Cohort 2 (Single-Agent Expansion) will evaluate the efficacy of lenvatinib at the RD in children, adolescents, and young adults with
Cohort 3A (Combination Dose-Finding) will determine the RD of lenvatinib in combination with ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma.
Cohort 3B (Combination Expansion) will evaluate the efficacy of lenvatinib at the RD from Cohort 3A in combination with ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma. Participants with osteosarcoma who have enrolled into Cohort 1 or 2B and experienced progressive disease will also be candidates for enrollment in Cohort 3B.
Lenvatinib will be provided as hard capsules containing 1, 4, or 10 mg lenvatinib. Lenvatinib capsules should be dissolved in water or apple juice for those who are unable to swallow capsules.
488 studies on the registry are indexed under Osteosarcoma; 124 are open to participants now.
This study's enrollment of 117 is above the median of 40 across 354 interventional studies indexed under Osteosarcoma.
Browse Osteosarcoma studies →Eisai Limited is the lead sponsor of 48 studies on the registry; 2 are open to participants now.
Compared within Osteosarcoma, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Neoplasms. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
or cytologically confirmed diagnosis of solid malignant tumor.
i) Papillary thyroid cancer (PTC). i.a) Follicular variant. i.b) Other variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hurthle cell variant of papillary carcinoma, or poorly differentiated carcinomas).
ii) Follicular thyroid cancer (FTC). ii.a) Hurthle cell. ii.b) Clear cell. ii.c) Insular.
c) Cohort 2B, 3A, and 3B: osteosarcoma.
Evaluable or that meets the following criteria:
DTC participants must be 131 iodine-refractory/ relapsed as defined by at least one of the following:
Adequate bone marrow function as evidenced by:
Adequate liver function as evidenced by:
Adequate renal function as evidenced by:
a) Serum creatinine based on age/gender as below. If serum creatinine is greater than maximum serum creatinine for age/gender as shown in the table below, then (or radioisotope [GFR]) must be greater than 70 milliliter/minute/1.73 square meter (mL/min/1.73 m2).
Maximum Serum Creatinine in milligrams/deciliter (mg/dL) for male:
i. Age 2 to less than 6 years = 0.8
ii. Age 6 to less than 10 years = 1.0
iii. Age 10 to less than 13 years = 1.2
iv. Age 13 to less than 16 years = 1.5
v. Age greater than or equal to 16 years = 1.7
Maximum Serum Creatinine (mg/dL) for Female:
vi. Age 2 to less than 6 years = 0.8
vii. Age 6 to less than 10 years = 1.0
viii. Age 10 to less than 13 years = 1.2
ix. Age 13 to less than 16 years = 1.4
x. Age greater than or equal to 16 years = 1.4
The threshold creatinine values in this Table were derived from the Schwartz formula for estimating glomerular filtration rate using child length and stature data published by the CDC.
b) Urine dipstick less than 2+ for proteinuria. Participants who have greater than or equal to 2+ proteinuria on dipstick urinalysis should undergo a spot protein-creatinine (P/C) ratio that should be Grade less than 2.
c) No clinical evidence of nephrotic syndrome.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as:
BP less than 95th percentile for sex, age, and height/length at screening (as per National Heart Lung and Blood Institute guidelines) and no change in antihypertensive medications within 1-week prior to Cycle 1/Day 1. Osteosarcoma subjects 18 to 25 years should have BP ≤150/90 mm Hg at screening and no change in antihypertensive therapy within 1 week prior to Cycle 1/Day 1.
Willing and able to comply with the protocol, scheduled follow-up, and management of toxicity as judged by the Investigator.
Cohort 3B (Combination Expansion): Osteosarcoma subjects who progressed in Cohorts 1 or 2B and opt to receive combination therapy.
Exclusion criteria:
Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
Cohort 3B (Combination Expansion): Osteosarcoma participants who progressed in Cohorts 1 or 2B and opt to receive combination therapy.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Children and adolescents with relapsed or refractory solid malignant tumors.
Drug: Lenvatinib
Children and adolescents with 131 iodine-refractory DTC.
Drug: Lenvatinib
Participants with relapsed or refractory osteosarcoma.
Drug: Lenvatinib
Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.
Drug: Lenvatinib · Drug: Ifosfamide · Drug: Etoposide
Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.
Drug: Lenvatinib · Drug: Ifosfamide · Drug: Etoposide
Cohort 1: Lenvatinib will be administered orally, once daily on Days 1 to 28 of each 28-day cycle at a starting dose of 11 mg/m2. Dose can be de-escalated to 9 mg/m2 or escalated to 14 and 17 mg/m2.
Also known as: E7080, lenvatinib
Cohort 2A: Lenvatinib (RD determined in Cohort 1) will be administered orally, once daily on Days 1 to 28 of each 28-day cycle.
Also known as: E7080, lenvatinib
Cohort 2B: Lenvatinib (RD determined in Cohort 1) will be administered orally, once daily on Days 1 to 28 of each 28-day cycle.
Also known as: E7080, lenvatinib
Cohort 3A: Lenvatinib will be administered orally, once daily on Days 1 to 21 of each 21-day cycle at 20% lower than RD determined in Cohort 1 (starting dose). Lenvatinib dose can be escalated to the RD from Cohort 1 or de-escalated to 40 and 60% lower than the RD from Cohort 1.
Also known as: E7080, lenvatinib
Cohort 3B: Lenvatinib will be administered orally, once daily on Days 1 to 21 of each 21-day cycle at the RD as determined in Cohort 3A.
Also known as: E7080, lenvatinib
Ifosfamide 3000 mg/m2/day (starting dose) will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. Ifosfamide dose can be de-escalated to 2400 mg/m2/day and 1800 mg/m2/day.
Etoposide 100 mg/m2/day (starting dose) will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. Etoposide dose can be de-escalated to 80 mg/m2/day and 60 mg/m2/day.
Ifosfamide dose identified in Cohort 3A will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.
Etoposide dose identified in Cohort 3A will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.
Cohort 1: Recommended Dose (RD) of Lenvatinib
RD was defined as the dose that had a dose limiting toxicity (DLT) rate closest to the targeted 20% rate. DLT was an adverse drug reaction and was assessed according to common terminology criteria for adverse events (CTCAE) version (v) 4.03 defined as 1) Grade 4 neutropenia for greater than or equal to (\>=) 7 days, 2) Grade \>=3 thrombocytopenia with bleeding, or lasting greater than (\>) 7 days, 3) Grade \>=3 febrile neutropenia, 4) Next course of chemotherapy delayed for \>=7 days, 5) Grade \>=3 non-hematologic toxicity persisting \>7 days optimal supportive care, 6) Grade 4 hypertension, confirmed systolic or diastolic blood pressure \>25 millimeters of mercury (mmHg) above the 95th percentile for age, or an elevated diastolic blood pressure (that is, \>95th percentile for age) not controlled by a single antihypertensive medication within 14 days of use, 7) Grade 3 proteinuria, 8) Any recurrent Grade 2 non-hematological toxicity requiring \>=2 interruption and dose reductions.
Time frame: Cycle 1 (28 days)
Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR)
OR was defined as participants with best overall response (BOR) of CR or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. For OR, the BOR was defined as the best response (CR or PR for \>4 weeks) recorded from the start of the treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From date of first dose of study drug until first documentation of PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)
Cohort 2A: Number of Participants With Best Overall Response (BOR)
BOR was defined as the best response of CR or PR for \>4 weeks or SD for \>=7 weeks recorded from the start of the treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From first dose of study drug until PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)
Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4
Progression free survival at Month 4 (PFS-4) rate was defined as the percentage of participants who were alive and without PD at Month 4 after the first dose of study drug, based on RECIST v1.1, using a binomial proportion with corresponding 95% confidence interval (CI). PD: \>= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of \>=5 mm. Appearance of \>=1 new lesions also considered PD.
Time frame: At Month 4
Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide
RD of lenvatinib when given in combination with ifosfamide and etoposide was defined as dose that resulted in no more than 1 DLT per 6 participants,or hematologic DLT in 1 participant and nonhematologic DLT in another participant per 6 participants,upon repeating same dose level.DLT was adverse drug reaction and assessed per CTCAE v4.03 defined as 1)Grade 4 neutropenia for \>=10 days,2)Grade \>=3 thrombocytopenia with bleeding,or lasting \>=10 days,3)Grade \>=3 febrile neutropenia lasting \>=7 days,4)Next course of chemotherapy delayed for \>=7 days,5)Grade \>=3 nonhematologic toxicity persisting \>7 days despite optimal supportive care,6)Grade 4 hypertension,confirmed systolic or diastolic blood pressure \>25 mmHg above 95th percentile for age,or elevated diastolic blood pressure(\>95th percentile for age)not controlled by single antihypertensive medication within 14 days use,7)Grade 3 proteinuria,8)Any recurrent Grade 2 nonhematological toxicity requiring \>=2 interruption and dose reductions.
Time frame: Cycle 1 (21 days)
Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR)
BOR: best response of CR or PR for \>4 weeks or SD for \>=7 weeks from first dose, recorded from start of treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have reduction in their short axis \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Not evaluable (NE) means BOR of NE or SD of \<7 weeks duration. Unknown means no data were available on the case report form.
Time frame: From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a BOR of CR or PR for \>4 weeks or SD for \>=7 weeks as assessed by investigator based on RECIST v1.1, recorded from start of study treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. 95% CI of the ORR were calculated according to Clopper and Pearson method.
Time frame: From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR)
DOR was defined as time in months from the first documentation confirmed CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. 95% CI for the median were calculated according to Brookmeyer and Crowley method.
Time frame: First documentation of CR/PR until first documentation of PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control
Participants were defined as having disease control if they had a BOR of CR or PR for \>4 weeks, or SD (minimum duration from first dose to SD \>=7 weeks) or if participants had a BOR of CR or Non-CR/Non-PD (minimum duration from first dose to Non-CR/Non-PD \>=7 weeks) per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest SOD. Non-CR/Non-PD: persistence of 1 or more non-target lesions, maintenance of tumor marker level above the normal limits.
Time frame: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit
Participants were defined as having clinical benefit if they had a BOR of CR or PR for \>4 weeks or durable SD (lasting \>=23 weeks) or if participants had a BOR of CR or durable Non-CR/Non-PD (lasting \>=23 weeks) as per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. Non-CR/Non-PD:persistence of 1 or more non-target lesions and maintenance of tumor marker level above the normal limits.
Time frame: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS)
PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of PD or date of death, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.
Time frame: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP)
TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.
Time frame: From first dose of study drug until PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS)
OS was defined as the time from the date of the first dose of study drug until the date of death from any cause. Participants who are lost to follow-up and those who are alive at the date of data cutoff were censored at the date the participant was last known to be alive (or the data cutoff date). 95% CI of median were calculated according to Brookmeyer and Crowley method.
Time frame: From first dose of study drug until death (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Number of participants with TEAEs (serious and non-serious adverse events) and SAEs were reported based on their safety assessments of hematology, clinical chemistry, proximal tibial growth, fecal occult blood, physical examinations, regular measurement of vital signs and electrocardiogram parameter values.
Time frame: From the date of first dose of study drug up to 30 days after the last dose (up to approximately 7 years)
Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria
An aliquot of the urine samples were collected to analyze protein by dipstick method, microscopic examination (if protein was abnormal). The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters of urine protein can be read as "negative, Trace, plus (+) 1, +2, +3 and +4" indicating proportional concentrations in the urine sample. The plus sign increases with a higher level of proteins in the urine.
Time frame: Baseline up to approximately 4 years 7 months
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score
Lansky Performance Play Scale rates a child's activity level for \<16 years of age. Scores on scale range from 0 (unresponsive) to 100 ( fully active, normal), where 100=fully active, normal; 90=minor restrictions in physically strenuous activity; 80=active, but tires more quickly; 70=both greater restriction of and less time spent in play activity; 60=up and around, but minimal active play, keeps busy with quieter activities; 50=gets dressed, but lies around much of day, no active play, able to participant in quiet play and activities; 40=mostly in bed, participates in quiet activities; 30=in bed, needs assistance even for quiet play; 20=often sleeping, play entirely limited to very passive activities; 10=no play, does not get out of bed; 0=unresponsive. Higher score indicates more activity and lower indicates less or no activity.
Time frame: Baseline up to approximately 4 years 7 months
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores
KPS: compare effectiveness of medicine for disease and assess outcomes in participants. KPS Scores: recorded on 11 point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100%), where 0=Dead; 10=moribund, fatal processes progressing rapidly; 20=very sick, hospital admission necessary, active supportive treatment necessary; 30=severely disabled, hospital admission is indicated although death not imminent; 40=disabled, requires special care/assistance; 50=requires considerable assistance/frequent medical care; 60=requires occasional assistance, but is able to care for personal needs; 70=cares for self, unable to carry normal activity or active work; 80=normal activity with effort, some signs of disease; 90=able to carry on normal activity, minor signs of disease; 100=normal no complaints, no evidence of disease. Lower score, worse survival for most serious illnesses.
Time frame: Baseline up to approximately 4 years 7 months
Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib
Duration of each cycle for Cohorts 1, 2A, 2B is 28 days. Duration of each cycle for Cohorts 3A, 3B is 21 days.
Time frame: Cohorts 1, 2A, 2B: Cycle(C)1 Day(D)1: 0.5-4 hours (h), 6-10 h post-dose, C1D15: pre-dose, 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose; Cohorts 3A, 3B: C1D1: 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose
Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level
Serum biomarkers included Fibroblast Growth Factor (FGF) 19, FGF 21, Vascular Endothelial Growth Factor (VEGF). In this outcome measure, percent change from baseline in serum biomarkers level per "PFS-4, Yes" and "PFS-4, No" have been reported. As per assessment of investigator based on RECIST v1.1, "PFS-4, Yes"= participants evaluable for PFS-4 month and alive and without PD at 4 months from the first dose, "PFS-4, No"=participants evaluable for PFS-4 month and not alive or with PD at 4 months from the first dose.
Time frame: Cohort 2B: Baseline, Cycle 2-3 Day 1 (Duration of each cycle=28 days); Cohort 3B: Baseline, Cycle 2 Day 1, Cycle 4 Day 1 (Duration of each cycle=21 days)
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure
TEAEs (serious and non-serious), those occurred most frequently have been reported in this outcome measure. "Palmar-plantar E syndrome" refers to Palmar-plantar erythrodysaesthesia syndrome.
Time frame: First dose of study drug until 30 days after last dose of study drug (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib
In acceptability questionnaire, participants were asked to answer the overall acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell and how does it feel in the mouth. Overall acceptability was answered in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. Overall acceptability was the overall acceptance for taste, appearance, smell, and the feeling in mouth. In this measure, number of participants have been reported per their overall acceptability responses.
Time frame: Cycle 1 Day 1 (Cycle length=28 days for Cohorts 1, 2A, 2B; Cycle length=21 days for Cohorts 3A, 3B)
Participants took part at 19 investigative sites in France, Germany, Italy, Spain, United Kingdom and the United States. Total 117 participants were enrolled and screened, of which 20 participants were screen failures and 97 participants received study treatment.
| Milestone | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Started | 3 | 9 | 11 | 1 | 31 | 7 | 15 | 20 |
| Underwent run-in period | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treated (safety population) | 5 | 11 | 7 | 1 | 31 | 11 | 11 | 20 |
| Completed | 1 | 3 | 4 | 1 | 2 | 0 | 5 | 4 |
| Not completed | 2 | 6 | 7 | 0 | 29 | 7 | 10 | 16 |
| Withdrew: Death | 2 | 6 | 7 | 0 | 27 | 7 | 9 | 14 |
| Withdrew: Withdrawal of consent | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 2 |
RD was defined as the dose that had a dose limiting toxicity (DLT) rate closest to the targeted 20% rate. DLT was an adverse drug reaction and was assessed according to common terminology criteria for adverse events (CTCAE) version (v) 4.03 defined as 1) Grade 4 neutropenia for greater than or equal to (\>=) 7 days, 2) Grade \>=3 thrombocytopenia with bleeding, or lasting greater than (\>) 7 days, 3) Grade \>=3 febrile neutropenia, 4) Next course of chemotherapy delayed for \>=7 days, 5) Grade \>=3 non-hematologic toxicity persisting \>7 days optimal supportive care, 6) Grade 4 hypertension, confirmed systolic or diastolic blood pressure \>25 millimeters of mercury (mmHg) above the 95th percentile for age, or an elevated diastolic blood pressure (that is, \>95th percentile for age) not controlled by a single antihypertensive medication within 14 days of use, 7) Grade 3 proteinuria, 8) Any recurrent Grade 2 non-hematological toxicity requiring \>=2 interruption and dose reductions.
| milligram per square meter (mg/m^2) | Cohort 1: All Participants |
|---|---|
| Cohort 1: Recommended Dose (RD) of Lenvatinib | 14 |
OR was defined as participants with best overall response (BOR) of CR or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. For OR, the BOR was defined as the best response (CR or PR for \>4 weeks) recorded from the start of the treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
| Participants | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 |
|---|---|
| Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) | 1 |
BOR was defined as the best response of CR or PR for \>4 weeks or SD for \>=7 weeks recorded from the start of the treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
| Participants | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 |
|---|---|
| Complete Response | 0 |
| Partial Response | 1 |
| Stable Disease | 0 |
Progression free survival at Month 4 (PFS-4) rate was defined as the percentage of participants who were alive and without PD at Month 4 after the first dose of study drug, based on RECIST v1.1, using a binomial proportion with corresponding 95% confidence interval (CI). PD: \>= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of \>=5 mm. Appearance of \>=1 new lesions also considered PD.
| percentage of participants | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|
| Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4 | 32.1 (15.9 to 52.4) | 66.7 (38.4 to 88.2) |
RD of lenvatinib when given in combination with ifosfamide and etoposide was defined as dose that resulted in no more than 1 DLT per 6 participants,or hematologic DLT in 1 participant and nonhematologic DLT in another participant per 6 participants,upon repeating same dose level.DLT was adverse drug reaction and assessed per CTCAE v4.03 defined as 1)Grade 4 neutropenia for \>=10 days,2)Grade \>=3 thrombocytopenia with bleeding,or lasting \>=10 days,3)Grade \>=3 febrile neutropenia lasting \>=7 days,4)Next course of chemotherapy delayed for \>=7 days,5)Grade \>=3 nonhematologic toxicity persisting \>7 days despite optimal supportive care,6)Grade 4 hypertension,confirmed systolic or diastolic blood pressure \>25 mmHg above 95th percentile for age,or elevated diastolic blood pressure(\>95th percentile for age)not controlled by single antihypertensive medication within 14 days use,7)Grade 3 proteinuria,8)Any recurrent Grade 2 nonhematological toxicity requiring \>=2 interruption and dose reductions.
| milligram per square meter (mg/m^2) | Cohort 3A: All Participants |
|---|---|
| Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide | 14 |
BOR: best response of CR or PR for \>4 weeks or SD for \>=7 weeks from first dose, recorded from start of treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have reduction in their short axis \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Not evaluable (NE) means BOR of NE or SD of \<7 weeks duration. Unknown means no data were available on the case report form.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|
| Complete Response | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Partial Response | 0 | 0 | 0 | 2 | 2 | 0 | 3 |
| Stable Disease | 2 | 5 | 4 | 13 | 3 | 10 | 9 |
| Progressive Disease | 1 | 2 | 4 | 12 | 2 | 2 | 4 |
| Not Evaluable or Unknown | 0 | 2 | 2 | 3 | 0 | 2 | 2 |
ORR was defined as the percentage of participants with a BOR of CR or PR for \>4 weeks or SD for \>=7 weeks as assessed by investigator based on RECIST v1.1, recorded from start of study treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. 95% CI of the ORR were calculated according to Clopper and Pearson method.
| percentage of participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|
| Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 0 (0.0 to 70.8) | 0 (0.0 to 33.6) | 0 (0.0 to 30.8) | 6.7 (0.8 to 22.1) | 28.6 (3.7 to 71.0) | 0 (0.0 to 23.2) | 16.7 (3.6 to 41.4) |
DOR was defined as time in months from the first documentation confirmed CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. 95% CI for the median were calculated according to Brookmeyer and Crowley method.
| months | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR) | — | — | — | 1.9 (NA to NA) | 4.6 (NA to NA) | NA (NA to NA) | — | NA (NA to NA) |
Participants were defined as having disease control if they had a BOR of CR or PR for \>4 weeks, or SD (minimum duration from first dose to SD \>=7 weeks) or if participants had a BOR of CR or Non-CR/Non-PD (minimum duration from first dose to Non-CR/Non-PD \>=7 weeks) per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest SOD. Non-CR/Non-PD: persistence of 1 or more non-target lesions, maintenance of tumor marker level above the normal limits.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 2 | 5 | 5 | 1 | 16 | 5 | 11 | 14 |
Participants were defined as having clinical benefit if they had a BOR of CR or PR for \>4 weeks or durable SD (lasting \>=23 weeks) or if participants had a BOR of CR or durable Non-CR/Non-PD (lasting \>=23 weeks) as per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. Non-CR/Non-PD:persistence of 1 or more non-target lesions and maintenance of tumor marker level above the normal limits.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 0 | 3 | 4 | 1 | 7 | 4 | 5 | 8 |
PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of PD or date of death, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.
| months | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 3.7 (0.5 to 5.0) | 6.3 (0.6 to 10.6) | 5.5 (1.4 to 11.3) | 5.5 (NA to NA) | 3.0 (1.8 to 5.4) | 7.1 (2.1 to NA) | 12.0 (11.1 to 16.1) | 6.9 (4.2 to NA) |
TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.
| months | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 3.7 (0.5 to 5.0) | 6.3 (0.6 to 10.6) | 5.5 (1.4 to 11.3) | 5.5 (NA to NA) | 3.0 (1.8 to 5.4) | 7.1 (2.1 to NA) | 12.0 (11.1 to 16.1) | 6.9 (4.2 to NA) |
OS was defined as the time from the date of the first dose of study drug until the date of death from any cause. Participants who are lost to follow-up and those who are alive at the date of data cutoff were censored at the date the participant was last known to be alive (or the data cutoff date). 95% CI of median were calculated according to Brookmeyer and Crowley method.
| months | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | 8.1 (3.8 to NA) | 7.4 (1.3 to NA) | 7.7 (2.7 to NA) | 6.1 (NA to NA) | 10.0 (5.6 to 12.3) | 13.6 (2.4 to 28.0) | NA (8.8 to NA) | NA (7.3 to NA) |
Number of participants with TEAEs (serious and non-serious adverse events) and SAEs were reported based on their safety assessments of hematology, clinical chemistry, proximal tibial growth, fecal occult blood, physical examinations, regular measurement of vital signs and electrocardiogram parameter values.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| TEAEs | 5 | 11 | 7 | 1 | 29 | 11 | 11 | 20 |
| SAEs | 3 | 7 | 5 | 1 | 21 | 7 | 9 | 16 |
An aliquot of the urine samples were collected to analyze protein by dipstick method, microscopic examination (if protein was abnormal). The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters of urine protein can be read as "negative, Trace, plus (+) 1, +2, +3 and +4" indicating proportional concentrations in the urine sample. The plus sign increases with a higher level of proteins in the urine.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Baseline: Trace, Worst Post baseline: Negative | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline: Trace, Worst Post baseline: Trace | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| Baseline: +1, Worst Post baseline: Negative | 2 | 3 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline: +1, Worst Post baseline: +1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline: Negative, Worst Post baseline: Negative | 0 | 1 | 0 | 1 | 4 | 0 | 4 | 2 |
| Baseline: +2, Worst Post baseline: Negative | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
| Baseline: +3, Worst Post baseline: Negative | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline: +3, Worst Post baseline: +1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline: +3, Worst Post baseline: +2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline: +3, Worst Post baseline: Trace | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline: +4, Worst Post baseline: Trace | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline: +4, Worst Post baseline: +1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Baseline: Negative, Worst Post baseline: Trace | 0 | 0 | 0 | 0 | 5 | 0 | 1 | 3 |
| Baseline: Negative, Worst Post baseline: +1 | 0 | 0 | 0 | 0 | 7 | 7 | 1 | 1 |
| Baseline: Negative, Worst Post baseline: +2 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 6 |
| Baseline: Negative, Worst Post baseline: +3 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 2 |
| Baseline: Trace, Worst Post baseline: +1 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 |
| Baseline: Trace, Worst Post baseline: +2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Baseline: Trace, Worst Post baseline: +3 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Baseline: +1, Worst Post baseline: Trace | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Baseline: +1, Worst Post baseline: +2 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 1 |
| Baseline: +1, Worst Post baseline: +3 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Baseline: Negative, Worst Post baseline: +4 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Baseline: +1, Worst Post baseline: +4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Lansky Performance Play Scale rates a child's activity level for \<16 years of age. Scores on scale range from 0 (unresponsive) to 100 ( fully active, normal), where 100=fully active, normal; 90=minor restrictions in physically strenuous activity; 80=active, but tires more quickly; 70=both greater restriction of and less time spent in play activity; 60=up and around, but minimal active play, keeps busy with quieter activities; 50=gets dressed, but lies around much of day, no active play, able to participant in quiet play and activities; 40=mostly in bed, participates in quiet activities; 30=in bed, needs assistance even for quiet play; 20=often sleeping, play entirely limited to very passive activities; 10=no play, does not get out of bed; 0=unresponsive. Higher score indicates more activity and lower indicates less or no activity.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Baseline score:100%, Worst Postbaseline score:90% | 3 | 0 | 0 | 0 | 1 | 1 | 1 | 0 |
| Baseline score: 70%, Worst Postbaseline score: 60% | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline score: 80%, Worst Postbaseline score: 60% | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 |
| Baseline score: 100%, Worst Postbaseline score:60% | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline score: 80%, Worst Postbaseline score: 70% | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 0 |
| Baseline score: 90%, Worst Postbaseline score: 70% | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Baseline score: 90%, Worst Postbaseline score: 80% | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 |
| Baseline score:100%, Worst Postbaseline score:100% | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 5 |
| Baseline score: 80%, Worst Postbaseline score: 40% | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline score: 70%, Worst Postbaseline score: 80% | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Baseline score: 80%, Worst Postbaseline score: 80% | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 2 |
| Baseline score: 100%, Worst Postbaseline score:80% | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Baseline score: 90%, Worst Postbaseline score: 90% | 0 | 0 | 0 | 0 | 4 | 0 | 1 | 2 |
| Baseline score: 60%, Worst Postbaseline score: 60% | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Baseline score: 90%, Worst Postbaseline score: 60% | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Baseline score: 70%, Worst Postbaseline score: 70% | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Baseline score: 90%, Worst Postbaseline score:100% | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Baseline score: 100%, Worst Postbaseline score:70% | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Baseline score: 80%, Worst Postbaseline score: 50% | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
KPS: compare effectiveness of medicine for disease and assess outcomes in participants. KPS Scores: recorded on 11 point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100%), where 0=Dead; 10=moribund, fatal processes progressing rapidly; 20=very sick, hospital admission necessary, active supportive treatment necessary; 30=severely disabled, hospital admission is indicated although death not imminent; 40=disabled, requires special care/assistance; 50=requires considerable assistance/frequent medical care; 60=requires occasional assistance, but is able to care for personal needs; 70=cares for self, unable to carry normal activity or active work; 80=normal activity with effort, some signs of disease; 90=able to carry on normal activity, minor signs of disease; 100=normal no complaints, no evidence of disease. Lower score, worse survival for most serious illnesses.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Baseline score: 100%, Worst Postbaseline score:80% | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 2 |
| Baseline score: 100%, Worst Postbaseline score:90% | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 2 |
| Baseline score: 70%, Worst Postbaseline score: 70% | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Baseline score: 90%, Worst Postbaseline score: 70% | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Baseline score: 80%, Worst Postbaseline score: 80% | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Baseline score: 90%, Worst Postbaseline score: 60% | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Baseline score:100%, Worst Postbaseline score:100% | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 |
| Baseline score: 100%, Worst Postbaseline score:70% | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Baseline score: 90%, Worst Postbaseline score: 80% | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Baseline score: 90%, Worst Postbaseline score: 90% | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 1 |
Duration of each cycle for Cohorts 1, 2A, 2B is 28 days. Duration of each cycle for Cohorts 3A, 3B is 21 days.
| nanogram per milliliter (ng/mL) | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1: 0.5-4 hours | 295.6 ± 214.01 | 134.8 ± 145.83 | 52.5 ± 81.40 | 11.1 ± NA | 177.4 ± 191.03 | 105.2 ± 131.54 | 111.4 ± 131.47 | 209.7 ± 197.66 |
| Cycle 1 Day 1: 6-10 hours | 212.7 ± 185.98 | 281.9 ± 137.39 | 238.0 ± 135.87 | 188 ± NA | 289.4 ± 200.09 | 191.9 ± 100.69 | 148.5 ± 122.41 | 164.8 ± 73.59 |
| Cycle 1 Day 15: Pre-dose | 46.9 ± 11.01 | 59.1 ± 29.19 | 96.9 ± 66.10 | 56.2 ± NA | 67.0 ± 53.78 | — | — | — |
| Cycle 1 Day 15: 0.5-4 hours | 133.4 ± 163.37 | 226.6 ± 204.61 | 191.8 ± 190.22 | 124 ± NA | 168.3 ± 157.67 | — | — | — |
| Cycle 1 Day 15: 6-10 hours | 351.8 ± 157.15 | 375.8 ± 121.21 | 413.0 ± 221.47 | 247 ± NA | 322.9 ± 138.87 | — | — | — |
| Cycle 2 Day 1: Pre-dose | 58.1 ± 19.58 | 61.6 ± 60.61 | 97.9 ± 77.08 | 59.8 ± NA | 66.8 ± 62.50 | 51.7 ± 44.23 | 76.1 ± 63.25 | 50.4 ± 65.10 |
| Cycle 2 Day 1: 2-12 hours | 502.4 ± 360.71 | 440.7 ± 229.29 | 339.2 ± 212.44 | 102 ± NA | 382.4 ± 217.49 | 205.6 ± 134.66 | 237.4 ± 124.82 | 275.3 ± 135.73 |
Serum biomarkers included Fibroblast Growth Factor (FGF) 19, FGF 21, Vascular Endothelial Growth Factor (VEGF). In this outcome measure, percent change from baseline in serum biomarkers level per "PFS-4, Yes" and "PFS-4, No" have been reported. As per assessment of investigator based on RECIST v1.1, "PFS-4, Yes"= participants evaluable for PFS-4 month and alive and without PD at 4 months from the first dose, "PFS-4, No"=participants evaluable for PFS-4 month and not alive or with PD at 4 months from the first dose.
| percent change | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|
| C2D1: FGF 19 (PFS-4, Yes) | 48.7 ± 110.78 | 172.1 ± 211.86 |
| C2D1: FGF 19 (PFS-4, No) | 109.9 ± 139.19 | 78.3 ± 203.30 |
| C3D1: FGF 19 (PFS-4, Yes) | 47.3 ± 130.42 | — |
| C3D1: FGF 19 (PFS-4, No) | 194.5 ± 180.71 | — |
| C4D1: FGF 19 (PFS-4, Yes) | — | 237.7 ± 204.94 |
| C4D1: FGF 19 (PFS-4, No) | — | 91.9 ± NA |
| C2D1: FGF 21 (PFS-4, Yes) | -14.9 ± 68.95 | 70.2 ± 138.90 |
| C2D1: FGF 21 (PFS-4, No) | 134.3 ± 203.81 | 7.2 ± 48.64 |
| C3D1: FGF 21 (PFS-4, Yes) | 55.0 ± 125.51 | — |
| C3D1: FGF 21 (PFS-4, No) | 17.0 ± 88.92 | — |
| C4D1: FGF 21 (PFS-4, Yes) | — | 256.2 ± 323.34 |
| C4D1: FGF 21 (PFS-4, No) | — | -1.5 ± NA |
| C2D1: VEGF (PFS-4, Yes) | 119.9 ± 309.01 | 87.9 ± 105.60 |
| C2D1: VEGF (PFS-4, No) | 124.2 ± 212.18 | 95.8 ± 92.53 |
| C3D1: VEGF (PFS-4, Yes) | 64.3 ± 153.50 | — |
| C3D1: VEGF (PFS-4, No) | 23.2 ± 69.67 | — |
| C4D1: VEGF (PFS-4, Yes) | — | 84.3 ± 97.85 |
TEAEs (serious and non-serious), those occurred most frequently have been reported in this outcome measure. "Palmar-plantar E syndrome" refers to Palmar-plantar erythrodysaesthesia syndrome.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Hypothyroidism | 3 | 6 | 3 | 0 | 13 | 5 | 6 | 6 |
| Abdominal pain | 2 | 2 | 1 | 1 | 5 | 6 | 5 | 6 |
| Diarrhea | 3 | 5 | 3 | 1 | 8 | 5 | 5 | 12 |
| Nausea | 1 | 2 | 3 | 0 | 8 | 7 | 8 | 13 |
| Vomiting | 1 | 6 | 3 | 0 | 7 | 5 | 6 | 12 |
| Asthenia | 2 | 1 | 0 | 0 | 8 | 0 | 0 | 7 |
| Fatigue | 2 | 2 | 3 | 0 | 8 | 2 | 4 | 3 |
| Alanine aminotransferase increased | 0 | 2 | 1 | 0 | 1 | 3 | 1 | 4 |
| Blood thyroid stimulating hormone increased | 0 | 0 | 0 | 0 | 9 | 3 | 0 | 5 |
| Weight decreased | 3 | 4 | 1 | 0 | 6 | 5 | 3 | 4 |
| Decreased appetite | 3 | 5 | 1 | 0 | 13 | 4 | 2 | 5 |
| Arthralgia | 0 | 2 | 1 | 0 | 1 | 2 | 4 | 1 |
| Myalgia | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
| Pain in extremity | 0 | 2 | 1 | 0 | 0 | 3 | 1 | 0 |
| Headache | 0 | 1 | 1 | 0 | 5 | 2 | 4 | 4 |
| Proteinuria | 0 | 3 | 3 | 0 | 7 | 2 | 5 | 8 |
| Dysphonia | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 |
| Erythema | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Hair color changes | 1 | 1 | 1 | 0 | 2 | 0 | 0 | 0 |
| Palmar-plantar E syndrome | 2 | 2 | 0 | 0 | 1 | 1 | 2 | 0 |
| Hypertension | 2 | 3 | 4 | 1 | 10 | 1 | 4 | 3 |
| Haematuria | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 4 |
| Hypokalaemia | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 2 |
| Hypophosphataemia | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 2 |
| Platelet count decreased | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 11 |
| Back pain | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 2 |
| Dry skin | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 |
| Oral pain | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1 |
| Pneumothorax | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1 |
| Dehydration | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 4 |
| Hypoalbuminaemia | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 |
| Lethargy | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 2 |
| Leukopenia | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 3 |
| Neutrophil count decreased | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 9 |
| Oral dysaesthesia | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 |
| Oropharyngeal pain | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 |
| Proctalgia | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 |
| Toxic encephalopathy | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Lymphocyte count decreased | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 4 |
| Abdominal pain upper | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 4 |
| Hyperuricemia | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Insomnia | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Anaemia | 0 | 0 | 0 | 0 | 0 | 9 | 7 | 15 |
| Neutropenia | 0 | 0 | 0 | 0 | 0 | 6 | 6 | 8 |
| Epistaxis | 0 | 0 | 0 | 0 | 0 | 5 | 4 | 4 |
| Thrombocytopenia | 0 | 0 | 0 | 0 | 0 | 5 | 4 | 5 |
| Febrile neutropenia | 0 | 0 | 0 | 0 | 0 | 5 | 3 | 2 |
| Stomatitis | 0 | 0 | 0 | 0 | 0 | 4 | 4 | 4 |
| Constipation | 0 | 0 | 0 | 0 | 0 | 5 | 2 | 2 |
| White blood cell count decreased | 0 | 0 | 0 | 0 | 0 | 4 | 3 | 12 |
| Lymphopenia | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Haematochezia | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Pyrexia | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Wound dehiscence | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Hypocalcaemia | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Dizziness | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Dyspnoea | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Hyperhidrosis | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
In acceptability questionnaire, participants were asked to answer the overall acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell and how does it feel in the mouth. Overall acceptability was answered in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. Overall acceptability was the overall acceptance for taste, appearance, smell, and the feeling in mouth. In this measure, number of participants have been reported per their overall acceptability responses.
| Participants | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|
| Super Good | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Really Good | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Good | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 1 |
| May be Good or May be Bad | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Bad | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Really Bad | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Super Bad | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Collected over From the date of first dose of study drug up to 30 days after the last dose (up to approximately 7 years). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Lenvatinib 5 mg/m^2 | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | 2/5 (40%) | 3/5 (60%) | 5/5 (100%) |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | 7/11 (63.6%) | 7/11 (63.6%) | 11/11 (100%) |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | 6/7 (85.7%) | 5/7 (71.4%) | 7/7 (100%) |
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | 27/31 (87.1%) | 21/31 (67.7%) | 29/31 (93.5%) |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | 10/11 (90.9%) | 7/11 (63.6%) | 11/11 (100%) |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | 6/11 (54.5%) | 9/11 (81.8%) | 11/11 (100%) |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | 14/20 (70%) | 16/20 (80%) | 20/20 (100%) |
| Event | Lenvatinib 5 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|
| Suicide attemptPsychiatric disorders | 0/2 | 0/5 | 0/11 | 0/7 | 1/1 | 0/31 | 0/11 | 0/11 | 0/20 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/2 | 0/5 | 0/11 | 0/7 | 0/1 | 0/31 | 5/11 | 3/11 | 2/20 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 0/2 | 0/5 | 0/11 | 2/7 | 0/1 | 0/31 | 0/11 | 1/11 | 0/20 |
| Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/2 | 0/5 | 3/11 | 0/7 | 0/1 | 0/31 | 0/11 | 0/11 | 0/20 |
| White blood cell count decreasedInvestigations | 0/2 | 0/5 | 0/11 | 0/7 | 0/1 | 0/31 | 0/11 | 0/11 | 5/20 |
| PneumoniaInfections and infestations | 0/2 | 1/5 | 1/11 | 0/7 | 0/1 | 0/31 | 1/11 | 0/11 | 0/20 |
| Platelet count decreasedInvestigations | 0/2 | 0/5 | 1/11 | 0/7 | 0/1 | 2/31 | 0/11 | 0/11 | 4/20 |
| Respiratory distressRespiratory, thoracic and mediastinal disorders | 0/2 | 1/5 | 0/11 | 0/7 | 0/1 | 1/31 | 0/11 | 0/11 | 0/20 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 0/2 | 1/5 | 0/11 | 0/7 | 0/1 | 4/31 | 2/11 | 2/11 | 3/20 |
| Urinary tract infectionInfections and infestations | 0/2 | 1/5 | 0/11 | 0/7 | 0/1 | 0/31 | 0/11 | 1/11 | 0/20 |
| Event | Lenvatinib 5 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|
| Abdominal painGastrointestinal disorders | 1/2 | 2/5 | 7/11 | 2/7 | 1/1 | 9/31 | 6/11 | 6/11 | 7/20 |
| DiarrhoeaGastrointestinal disorders | 1/2 | 4/5 | 5/11 | 4/7 | 1/1 | 12/31 | 8/11 | 6/11 | 13/20 |
| StomatitisGastrointestinal disorders | 0/2 | 1/5 | 0/11 | 0/7 | 1/1 | 4/31 | 5/11 | 3/11 | 4/20 |
| PyrexiaGeneral disorders | 1/2 | 2/5 | 4/11 | 4/7 | 1/1 | 11/31 | 6/11 | 3/11 | 6/20 |
| RhinitisInfections and infestations | 2/2 | 1/5 | 2/11 | 3/7 | 0/1 | 4/31 | 1/11 | 1/11 | 2/20 |
| Alanine aminotransferase increasedInvestigations | 0/2 | 0/5 | 4/11 | 2/7 | 1/1 | 1/31 | 3/11 | 1/11 | 5/20 |
| Aspartate aminotransferase increasedInvestigations | 0/2 | 0/5 | 3/11 | 2/7 | 1/1 | 2/31 | 1/11 | 1/11 | 3/20 |
| Back painMusculoskeletal and connective tissue disorders | 0/2 | 1/5 | 4/11 | 2/7 | 1/1 | 10/31 | 6/11 | 4/11 | 5/20 |
| DizzinessNervous system disorders | 0/2 | 0/5 | 1/11 | 0/7 | 1/1 | 3/31 | 1/11 | 3/11 | 2/20 |
| EpistaxisRespiratory, thoracic and mediastinal disorders | 0/2 | 2/5 | 3/11 | 2/7 | 1/1 | 4/31 | 5/11 | 6/11 | 7/20 |
Full analysis set included all enrolled participants who did not fail study screening.
| Age, Customized(Participants) | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|
| 2 to <6 years | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
| 6 to <18 years | 2 | 8 | 11 | 1 | 24 | 5 | 11 | 15 | 77 |
| 18 to <=25 years | 0 | 0 | 0 | 0 | 7 | 2 | 3 | 5 | 17 |
| Sex: Female, Male(Participants) | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Female | 1 | 5 | 5 | 0 | 18 | 2 | 5 | 7 | 43 |
| Male | 2 | 4 | 6 | 1 | 13 | 5 | 10 | 13 | 54 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 2 | 0 | 4 | 1 | 4 | 3 | 16 |
| Not Hispanic or Latino | 1 | 4 | 4 | 0 | 15 | 5 | 8 | 10 | 47 |
| Unknown or Not Reported | 1 | 4 | 5 | 1 | 12 | 1 | 3 | 7 | 34 |
| Race (NIH/OMB)(Participants) | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 2 | 5 | 3 | 1 | 20 | 6 | 14 | 13 | 64 |
| More than one race | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 3 | 6 |
| Unknown or Not Reported | 1 | 4 | 7 | 0 | 9 | 1 | 1 | 4 | 27 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Dec 2014 to primary completion in Jul 2019, 54 months.
Results were first posted in Sep 2020, 1 year 1 month after primary completion.
Of 33 phase 1/2 interventional studies under Osteosarcoma, half reached primary completion within 77 months of starting (the median), counting those still running; a quarter within 40 and three quarters within 92. This study's 54 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Lenvatinib