A Multicenter, Open-label, Randomized 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 (OLIE)
Overview
- Phase
- Phase 2
- Intervention
- Lenvatinib
- Conditions
- Osteosarcoma
- Sponsor
- Eisai Inc.
- Enrollment
- 81
- Locations
- 84
- Primary Endpoint
- Progression-free Survival (PFS) by Independent Imaging Review (IIR) Assessment
- Status
- Completed
- Last Updated
- last year
Overview
Brief 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.
Investigators
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.
- •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 (\<)16 years of age. Participants who are unable to walk because of paralysis, but who are able to perform activities of daily living while wheelchair bound, will be considered ambulatory for the purpose of assessing the performance score
- •Adequate organ function per blood work
- •Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) \>=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 \<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
- •Participants \>18 years of age should have BP less than or equal to (\<=) 150/90 millimeters of Mercury at screening and no change in antihypertensive therapy within 1 week prior to Cycle 1 Day 1
Exclusion Criteria
- •Any active infection or infectious illness unless fully recovered prior to Cycle 1 Day 1 (that is, no longer requiring systemic treatment)
- •Participants with central nervous system metastases are not eligible, unless they have completed local therapy (example, whole brain radiation therapy, surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 2 weeks before Cycle 1 Day 1
- •Active second malignancy within 2 years prior to enrollment (\[in addition to osteosarcoma\], but not including definitively treated superficial melanoma, carcinoma-in-situ, basal or squamous cell carcinoma of the skin)
- •Has had major surgery within 3 weeks prior to Cycle 1 Day
- •Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
- •A clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT or corrected QT (QTc) interval (example, a repeated demonstration of a QTc interval greater than \[\>\] 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
Arms & Interventions
Randomization Phase: Lenvatinib + Ifosfamide + Etoposide
Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.
Intervention: Lenvatinib
Randomization Phase: Lenvatinib + Ifosfamide + Etoposide
Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.
Intervention: Ifosfamide
Randomization Phase: Lenvatinib + Ifosfamide + Etoposide
Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.
Intervention: Etoposide
Randomization Phase: Ifosfamide + Etoposide
Participants with relapsed or refractory osteosarcoma will receive ifosfamide with etoposide. Participants with relapsed or refractory osteosarcoma may receive optional lenvatinib plus or minus chemotherapy (Ifosfamide and Etoposide) if disease progression is observed in study.
Intervention: Ifosfamide
Randomization Phase: Ifosfamide + Etoposide
Participants with relapsed or refractory osteosarcoma will receive ifosfamide with etoposide. Participants with relapsed or refractory osteosarcoma may receive optional lenvatinib plus or minus chemotherapy (Ifosfamide and Etoposide) if disease progression is observed in study.
Intervention: Etoposide
Randomization Phase: Ifosfamide + Etoposide
Participants with relapsed or refractory osteosarcoma will receive ifosfamide with etoposide. Participants with relapsed or refractory osteosarcoma may receive optional lenvatinib plus or minus chemotherapy (Ifosfamide and Etoposide) if disease progression is observed in study.
Intervention: Lenvatinib
Outcomes
Primary Outcomes
Progression-free Survival (PFS) by Independent Imaging Review (IIR) Assessment
Time Frame: From the date of randomization to the date of the first documentation of PD or date of death, whichever occurred first (up to 20.5 months)
PFS as assessed by IIR was defined as the time from the date of randomization to the date of the first documentation of PD or date of death (whichever occurred first), as determined using RECIST v1.1. PD was defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was analyzed using Kaplan-Meier method.
Secondary Outcomes
- Percentage of Participants With PFS at Month 4 (PFS-4m Rate) by IIR Assessment(Month 4)
- Objective Response Rate at Month 4 (ORR-4m) by IIR Assessment(Month 4)
- Change From Baseline in PedsQL Scale: Cancer Module Scale Score at Month 4(Baseline and Month 4)
- Percentage of Participants With PFS at 1 Year or Month 12 (PFS-1y Rate) by IIR Assessment(Month 12 or 1 Year)
- Percentage of Participants With Overall Survival at 1 Year or Month 12 (OS-1y)(Month 12 or 1 Year)
- Overall Survival (OS)(From the date of randomization to the date of death from any cause (up to 37.1 months))
- ORR by IIR Assessment(From the date of randomization to the date of the first documentation of CR or PR (up to 20.5 months))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first dose up to 30 days after the last dose of study drug (up to 40.8 months))
- Treatment Arm A: Plasma Concentration of Lenvatinib(Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: Pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: Pre-dose (each Cycle length = 21 days))
- Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Scale: Generic Core Scale Score at Month 4(Baseline and Month 4)
- Number of Participants Categorized Based on Overall Palatability and Acceptability Questionnaire Responses for Suspension of Lenvatinib(Cycle 1 Day 1 (Cycle length = 21 days))