Phase 2
N=81
A Study to Compare the Efficacy and Safety of Ifosfamide and Etoposide With or Without Lenvatinib in Children, Adolescents and Young Adults With Relapsed and Refractory Osteosarcoma
Osteosarcoma
Bottom Line
View on ClinicalTrials.gov: NCT04154189 ↗Enrolled (actual)
81
Serious AEs
63.8%
Results posted
Aug 2023
Primary outcome: Primary: Progression-free Survival (PFS) by Independent Imaging Review (IIR) Assessment — 6.5; 5.5 months — p=0.0396
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lenvatinib (Drug); Ifosfamide (Drug); Etoposide (Drug)
- Age
- Pediatric, Adult · 2+ yrs
- Sex
- All
- Sponsor
- Eisai Inc.
- Primary completion
- Jun 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) by Independent Imaging Review (IIR) Assessment |
6.5; 5.5 | 0.0396 sig |
| SECONDARY Percentage of Participants With PFS at Month 4 (PFS-4m Rate) by IIR Assessment |
76.3; 66.0 | 0.1683 |
| SECONDARY Percentage of Participants With PFS at 1 Year or Month 12 (PFS-1y Rate) by IIR Assessment |
NA; 14.9 | — |
| SECONDARY Overall Survival (OS) |
12.4; 17.2 | 0.3924 |
| SECONDARY Percentage of Participants With Overall Survival at 1 Year or Month 12 (OS-1y) |
49.2; 72.1 | 0.0352 sig |
| SECONDARY Objective Response Rate at Month 4 (ORR-4m) by IIR Assessment |
15.0; 7.3 | — |
| SECONDARY ORR by IIR Assessment |
15.0; 9.8 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
38; 39; 30; 20 | — |
| SECONDARY Treatment Arm A: Plasma Concentration of Lenvatinib |
147.9; 217.8; 70.7; 222.3; 310.9; 70.2 | — |
| SECONDARY Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Scale: Generic Core Scale Score at Month 4 |
2.61; 2.65 | — |
| SECONDARY Change From Baseline in PedsQL Scale: Cancer Module Scale Score at Month 4 |
2.66; 2.08 | — |
| SECONDARY Number of Participants Categorized Based on Overall Palatability and Acceptability Questionnaire Responses for Suspension of Lenvatinib |
0; 0; 0; 2; 2; 0 | — |
Summary
This Is a Multicenter, Randomized, Open-Label, Parallel-Group, Phase 2 Study to Compare the Efficacy and Safety of Lenvatinib in Combination with Ifosfamide and Etoposide Versus Ifosfamide and Etoposide in Children, Adolescents, and Young Adults with Relapsed or Refractory Osteosarcoma.
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed diagnosis of high grade osteosarcoma
- Refractory or relapsed osteosarcoma after 1 to 2 prior lines of systemic treatments
- Measurable or evaluable disease per RECIST 1.1.
- Life expectancy of 12 weeks or more
- Lansky play score greater than or equal to (>=) 50 Percent (%) or Karnofsky Performance Status score >=50%. Use Karnofsky for participants >=16 years of age and Lansky for participants less than ( =50% at baseline as determined by echocardiography or multigated acquisition (MUGA) scan
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as:
BP 18 years of age should have BP less than or equal to ( ] 480 millisecond [msec])
- 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
- Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib
- Pre-existing Grade >=3 gastrointestinal or non-gastrointestinal fistula
- Gastrointestinal bleeding or active hemoptysis (bright red blood of at least 1 divided [/] by 2 teaspoon) within 3 weeks prior to Cycle 1 Day 1
- 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
- History of ifosfamide-related Grade >=3 nephrotoxicity or encephalopathy
- Known to be human immunodeficiency virus (HIV) positive
- Known active Hepatitis B (example, Hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (example, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected). Note: Testing for Hepatitis B or Hepatitis C is required at screening only when mandated by local health authority
Data sourced from ClinicalTrials.gov (NCT04154189). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.