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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

NCT04154189

Description:

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.

Related Conditions:
  • Osteosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: E7080-G000-230
  • SECONDARY ID: 2019-003696-19
  • NCT ID: NCT04154189

Conditions

  • Osteosarcoma

Interventions

DrugSynonymsArms
LenvatinibE7080Randomization Phase: Lenvatinib + Ifosfamide + Etoposide
IfosfamideRandomization Phase: Ifosfamide + Etoposide
EtoposideRandomization Phase: Ifosfamide + Etoposide

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Randomization Phase: Lenvatinib + Ifosfamide + EtoposideExperimentalParticipants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.
  • Lenvatinib
  • Ifosfamide
  • Etoposide
Randomization Phase: Ifosfamide + EtoposideActive ComparatorParticipants with relapsed or refractory osteosarcoma will receive ifosfamide with etoposide.
  • Ifosfamide
  • Etoposide

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed diagnosis of high grade osteosarcoma

          2. Refractory or relapsed osteosarcoma after 1 to 2 prior systemic treatments

          3. Measurable or evaluable disease per RECIST 1.1.

          4. Life expectancy of 12 weeks or more

          5. 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 up in a wheelchair, will be considered
             ambulatory for the purpose of assessing the performance score

          6. Adequate organ function per blood work

          7. Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF)
             >=50% at baseline as determined by echocardiography

          8. 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 1. 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

          9. Washout before Cycle 1 Day 1 of 3 weeks in case of prior chemotherapy, 6 weeks if
             treatment included nitrosoureas; 4 weeks for definitive radiotherapy, 2 weeks for
             palliative radiotherapy; and 3 months from high-dose chemotherapy and stem cell
             rescue. Participants must have recovered [to Grade <=1, except for alopecia,
             ototoxicity, and Grade <=2 peripheral neuropathy, per common terminology criteria for
             adverse events (CTCAE) v5.0] from the acute toxic effects of all prior anticancer
             therapy before Cycle 1 Day 1

        Exclusion Criteria:

          1. Any active infection or infectious illness unless fully recovered prior to Cycle 1 Day
             1 (that is, no longer requiring systemic treatment)

          2. 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

          3. 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)

          4. Has had major surgery within 3 weeks prior to Cycle 1 Day 1. Note: Adequate wound
             healing after major surgery must be assessed clinically, independent of time elapsed
             for eligibility

          5. A clinically significant electrocardiogram (ECG) abnormality, including a marked
             baseline prolonged QT or QTc interval (example, a repeated demonstration of a QTc
             interval greater than [>] 480 millisecond [msec])

          6. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition
             that in the opinion of the investigator might affect the absorption of lenvatinib

          7. Pre-existing Grade >=3 gastrointestinal or non-gastrointestinal fistula

          8. 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

          9. 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

         10. History of ifosfamide-related Grade >=3 nephrotoxicity or encephalopathy

         11. Known to be human immunodeficiency virus (HIV) positive

         12. Active viral hepatitis (B or C) as demonstrated by positive serology
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival Rate at Month 4 (PFS-4m Rate)
Time Frame:Month 4
Safety Issue:
Description:PFS-4m by independent imaging review (IIR) is defined as the percentage of participants who will be alive and without PD at 4 months from the randomization date as determined by IIR of radiological imaging using RECIST 1.1.

Secondary Outcome Measures

Measure:Progression-free Survival Rate at 1 Year or Month 12 (PFS-1y rate)
Time Frame:Month 12
Safety Issue:
Description:Progression-free survival rate at 1 year or 12 months (PFS-1y rate) by IIR is defined as the percentage of participants who will be alive and without PD at 1 year from the randomization date as determined by IIR of radiological imaging using RECIST 1.1.
Measure:Progression-free Survival (PFS)
Time Frame:From the date of randomization to the date of the first documentation of PD or death, whichever occurs first (up to approximately 36 months)
Safety Issue:
Description:PFS by IIR is defined as the time from the date of randomization to the date of the first documentation of PD or death (whichever occurs first) as determined by IIR using RECIST 1.1.
Measure:Overall Survival (OS)
Time Frame:From the date of randomization to the date of death from any cause (up to approximately 36 months)
Safety Issue:
Description:OS is defined as the time from the date of randomization to the date of death from any cause.
Measure:Objective Response Rate (ORR)
Time Frame:Month 4
Safety Issue:
Description:ORR by IIR at 4 months is defined as the percentage of participants who will have best overall response of complete response (CR) or partial response (PR) as determined by IIR using RECIST 1.1 within the first 4 months.
Measure:Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame:From Baseline up to 30 days after the last dose of study drug or until resolution, whichever comes first (up to approximately 36 months)
Safety Issue:
Description:
Measure:Plasma Concentration of Lenvatinib - Arm A
Time Frame:Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 15: Predose, 0.5-4 hours and 6-10 hours postdose; Cycle 2 Day 1: Predose (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Change From Baseline in Score for all Pediatric Quality of Life Inventory (PedsQL) Scales Including Generic Core Scales and Cancer Modules
Time Frame:Up to approximately 36 months
Safety Issue:
Description:Health-Related Quality of Life (HRQOL): The PedsQL is a modular instrument designed to measure HRQoL in pediatric and adults population. The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease specific modules. The PedsQL 3.0 Cancer Module was designed to measure pediatric cancer specific HRQOL.
Measure:Palatability and Acceptability of the Suspension Formulation of Lenvatinib in Participants Receiving the Suspension Formulation, as Assessed Using Palatability Questionnaire
Time Frame:Cycle 1 Day 1 (Cycle length = 21 days)
Safety Issue:
Description:The palatability and acceptability of the suspension formulation questionnaire will assess the following parameters: taste, appearance, smell, how does it feel in the mouth and overall acceptability. Each parameter will be measured using a 7-point Hedonic scale which is a Visual Analog Scale (VAS) grading parameters according to the following values: super bad, really bad, bad, may be good or may be bad, good, really good, or super good. For each parameter, the percentage of responses per grading value will be described.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Inc.

Trial Keywords

  • Osteosarcoma
  • Lenvatinib
  • Ifosfamide
  • Etoposide
  • E7080
  • Relapsed or Refractory Osteosarcoma
  • Pediatrics
  • Chemotherapy

Last Updated

July 10, 2020