AI-Powered Research

1. Histologically or cytologically confirmed diagnosis of high grade
osteosarcoma.
2. Refractory or relapsed osteosarcoma after 1 to 2 prior lines of systemic
treatments.
3. Measurable or evaluable disease per RECIST 1.1 that meets the following
criteria:
- Measurable disease is defined as a lesion with a minimum size (by long axis)
of 10 mm using computed tomography/magnetic resonance imaging (CT/MRI) (lymph
nodes must be accurately measurable with a minimum size [by short axis] of 15
mm).
- Lesions that have had external beam radiotherapy (EBRT) or locoregional
therapies such as radiofrequency (RF) ablation must have subsequently grown
unequivocally to be deemed a target lesion.
- Any other non-measurable lesions will be considered evaluable disease.
4. Aged 2 years to <=25 years at the time of informed consent.
5. Life expectancy of 12 weeks or more.
6. Lansky play score >=50% or Karnofsky Performance Status score >= 50%. Use
Karnofsky for subjects >=16 years of age and Lansky for subjects <16 years of
age. Subjects who are unable to walk because of paralysis, but who are able to
perform Activities of Daily Living (ADL) while wheelchair bound, will be
considered ambulatory for the purpose of assessing the performance score.
7. Adequate bone marrow function as evidenced by:
a. absolute neutrophil count (ANC) >=1.5×10^9/L. (subjects with bone marrow
involvement should have ANC >=0.8×10^9/L and leucocyte count >=1×10^9/L).
b. hemoglobin >=8.0 g/dL (a hemoglobin of <8.0 g/dL is acceptable if it is
corrected by growth factor or transfusion before Cycle 1 Day 1).
c. platelet count >=100×10^9/L. 8. Adequate blood coagulation function defined
by International
Normalized ratio or prothrombin time (INR/PT) and activated partial
thromboplastin time or partial thromboplastin time (aPTT/PTT) <=1.5 unless
participant is receiving anticoagulant therapy, as long as INR/PT and aPTT/PTT
are within therapeutic range of intended use of anticoagulants.
9. Adequate liver function as evidenced by:
a. Bilirubin <=1.5 times the upper limit of normal (ULN).
b. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <=3×ULN
(in the case of liver metastases <=5×ULN).
10. 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
within the protocol page 5, then creatinine clearance (or radioisotope
glomerular filtration rate [GFR]) must be >70 mL/min/1.73 m2.
b. Urine dipstick <2+ for proteinuria. Subjects who have >=2+ proteinuria on
dipstick urinalysis should undergo a spot protein-creatinine (P/C) ratio test
that should be Grade <2 per Common Terminology Criteria for Adverse Events
(CTCAE) v5.0 and if possible perform a 24-hour urine
collection (children and adolescents <=12 years of age must have <=500 mg of
protein/24 hours and subjects >12 years of age must have <=1 g of protein/24
hours).
c. No clinical evidence of nephrotic syndrome.
11. Adequate cardiac function as evidenced by left ventricular ejection
fraction >=50% at baseline as determined by echocardiography or multigated
acquisition (MUGA) scan.
12. Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as:
a. BP <95th perce

Exclusion Criteria

1. Any active infection or infectious illness unless fully recovered prior to
Cycle 1 Day 1.
2. Subjects with central nervous system metastases are not eligible, unless
they have completed local therapy and have discontinued the use of
corticosteroids for this indication at least 2 weeks before C1D1
3. Active second malignancy within 2 years prior to enrollment
4. Any medical or other condition that in the opinion of the investigator(s)
would preclude the subject's participation in a clinical study.
5. Has had major surgery within 3 weeks prior to Cycle 1 Day 1.
6. Known hypersensitivity to any component(s) of the study drugs (lenvatinib,
ifosfamide, and etoposide, or their ingredients).
7. Currently receiving any investigational drug or device in another clinical
study or within 28 days prior to Cycle 1 Day 1.
8. A clinically significant ECG abnormality, including a marked baseline
prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval >
480 msec).
9. Has clinically significant cardiovascular disease within 6 months from first
dose of study intervention, including New York Heart Association Class III or
IV congestive heart failure, unstable angina, myocardial infarction, cerebral
vascular accident, or cardiac arrhythmia associated
with hemodynamic instability. Note: Medically controlled arrhythmia would be
permitted.
10. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
condition that in the opinion of the investigator might affect the absorption
of lenvatinib.
11. Pre-existing Grade >=3 gastrointestinal or non-gastrointestinal fistula.
12. Gastrointestinal bleeding or active hemoptysis (bright red blood of at
least * teaspoon) within 3 weeks prior to Cycle 1 Day 1.
13. Radiographic evidence of intratumoral cavitation, encasement, or invasion
of a major blood vessel. Additionally, the degree of proximity to major blood
vessels should be considered for exclusion because of the potential risk of
severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib
therapy.
14. History of ifosfamide-related Grade >=3 nephrotoxicity or encephalopathy.
15. Evidence of clinically significant disease (eg, cardiac, respiratory,
gastrointestinal, renal disease) that in the opinion of the investigator(s)
could affect the subject's safety or interfere with the study assessments.
16. Known to be human immunodeficiency virus (HIV) positive. Note: HIV testing
is required at screening only when mandated by local authority.
17. Known active Hepatitis B (eg, HBsAg reactive) or Hepatitis C (eg, HCV RNA
[qualitative] is detected). Note: Testing for Hepatitis B or Hepatitis C is
required at screening only when mandated by local health authority.
18. Females who are breastfeeding or pregnant at Screening or Baseline (as
documented by a positive beta-human chorionic gonadotropin [ßhCG]) (human
chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or
equivalent units of ß-hCG /hCG]). A separate baseline assessment is required if
a negative screening pregnancy test was obtained more than 72 hours before the
first dose of any study drug.
19. Females of childbearing potential* who:
- Do not agree to use a highly effective method of contraception for the entire
study period and for 28 days after lenvatinib disco

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>PFS (progression-free survival) by IIR is defined as the time from the date of<br /><br>randomization to the date of the first documentation of PD or death (whichever<br /><br>occurs first) as determined by IIR using RECIST 1.1.</p><br>

Secondary Outcome Measures

Name	Time	Method

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