OsteosarcomaPhase 2NCT04154189
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
A Phase 2 study testing Lenvatinib, Ifosfamide and Etoposide in people with Osteosarcoma, run by Eisai Inc. at 84 sites in 21 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- Lenvatinib, Ifosfamide and Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 84 sitesin 21 countries
- Study dates
- 23 Mar 2020to 17 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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 (<)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
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- 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 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
- 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. For all other anti-cancer therapies, washout before Cycle 1 Day 1 of at least 5 half-lives (or at least 28 days, whichever is shorter). 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
- Must have no prior history of lenvatinib treatment
- Eligibility for optional lenvatinib crossover:
- Disease progression per RECIST 1.1 (as confirmed by IIR for all participants who crossover prior to the study data-cut)
- No new systemic anti-cancer medication administered after the last dose of study drugs
- Meets all safety parameters listed in the inclusion criteria and none listed in the exclusion criteria
- Study is ongoing
Who cannot join
- 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 1. 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
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- 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
Trial locations and contacts
84 sites in 21 countries.
84 sites in 21 countries
United States16 sites
Childrens Hospital Colorado
Aurora, Colorado, 80045
Children's of Alabama
Birmingham, Alabama, 35233
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Medical Center Dallas
Dallas, Texas, 75235
Cook Children's Health Care System
Fort Worth, Texas, 76104
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital For Children
Indianapolis, Indiana, 46202
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Loma Linda University Medical Center
Loma Linda, California, 92354
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Children's Hospital of Orange County
Orange, California, 92868
UCSF Benioff Children's Hospitals
San Francisco, California, 94143
Children's National Medical Center
Washington D.C., District of Columbia, 20010
France12 sites
Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin
Bordeaux
Centre Oscar Lambret
Lille
Centre Léon Berard
Lyon
Hopitaux de La Timone
Marseille
Hôpital de La Mère Et de L'enfant
Nantes
CHU de Nice
Nice
Hôpital Armand Trousseau
Paris
Institut Curie
Paris
Hopital de Hautepierre
Strasbourg
Hôpital Des Enfants
Toulouse
CHRU Nancy
Vandœuvre-lès-Nancy
Institut Gustave Roussy
Villejuif
United Kingdom10 sites
Birmingham Children's Hospital
Birmingham
The Royal Hospital for Children
Bristol
Royal Hospital for Children
Glasgow
Leeds Children Hospital
Leeds
Alder Hey Children's Hospital
Liverpool
UCL Cancer Institute
London
Royal Manchester Childrens Hospital
Manchester
The Christie NHS Foundation Trust
Manchester
Royal Victoria Infirmary
Newcastle
John Radcliffe Hospital
Oxford
Spain8 sites
Hospital Universitario de Cruces
Barakaldo
Hospital Sant Joan de Deu
Barcelona
Hospital Universitario Vall d'Hebrón
Barcelona
Hospital Infantil Universitario Niño Jesus
Madrid
Hospital Universitario Fundacion Jimenez Diaz
Madrid
Hospital Universitario La Paz
Madrid
Hospital Universitario Virgen del Rocio
Seville
Hospital Universitari i Politecnic La Fe de Valencia
Valencia
Australia5 sites
Chris O'Brien Lifehouse Hospital
Camperdown
Perth Childrens Hospital
Nedlands
Royal Children's Hospital Melbourne
Parkville
Queensland Children's Hospital
South Brisbane
Children's Hospital at Westmead
Westmead
Italy5 sites
Istituti Ortopedici Rizzoli
Bologna
Azienda Ospedaliera A Meyer
Florence
Istituto Giannina Gaslini
Genova
Istituto Nazionale Dei Tumori
Milan
IRCCS Ospedale Pediatrico Bambino Gesù
Roma
South Korea5 sites
National Cancer Center
Goyang-si
Asan Medical Center
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Severance Hospital Yonsei University Health System
Seoul
Singapore3 sites
KK Women's and Children's Hospital
Singapore
National Cancer Centre
Singapore
National University Hospital
Singapore
Sweden3 sites
Drottning Silvias Barn Och Ungdomssjukhus
Gothenburg
Skanes Universitetssjukhus Lund
Lund
Karolinska Universitetssjukhuset Solna
Stockholm
Czechia2 sites
FN Brno 2 Detska Klinika
Brno
Fakultní nemocnice v Motole
Prague
Hong Kong2 sites
Hong Kong Children's Hospital
Hong Kong
Prince of Wales Hospital
Hong Kong
New Zealand2 sites
Auckland City Hospital
Auckland
Starship Children's Hospital
Auckland
Switzerland2 sites
Centre Hospitalier Universitaire Vaudois
Lausanne
Kinderspital Zürich - Eleonorenstiftung
Zurich
Taiwan2 sites
National Taiwan University Hospital
Taipei
Taipei Veterans General Hospital
Taipei
Finland1 site
Tampereen yliopistollinen sairaala
Tampere, Länsi-Suomen Lääni, FI-33520
About this study
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)
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.
- Conditions
- Osteosarcoma
- Being tested
- Lenvatinib, Ifosfamide, Etoposide
- Keywords
- Osteosarcoma, Lenvatinib, Ifosfamide, Etoposide, E7080, Relapsed or Refractory Osteosarcoma, Pediatrics, Chemotherapy
- Medical subject headings
- Osteosarcoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080
Lenvatinib 14 milligrams per square meter (mg/m^2) capsules will be administered once daily on Days 1 to 21 of each 21-day cycle until disease progression (PD), development of unacceptable toxicity, participant request, withdrawal of consent, or discontinuation of study by the sponsor.
An extemporaneous suspension of lenvatinib capsules may be used for participants unable to swallow capsules.
IfosfamideDrug
Ifosfamide 3000 milligrams per square meter per day (mg/m^2/day) intravenous infusion will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.
EtoposideDrug
Etoposide 100 mg/m^2/day intravenous infusion will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.
LenvatinibDrug
Also called E7080
Lenvatinib 14 mg/m^2 capsules will be administered once daily on Days 1 to 21 of each 21-day cycle until the next PD (per response evaluation criteria in solid tumors [RECIST] 1.1 as assessed by investigator), development of unacceptable toxicity, participant request, or withdrawal of consent, whichever occurs first.
| Study group | Role | What they receive |
|---|---|---|
| Randomization Phase: Lenvatinib + Ifosfamide + Etoposide | Experimental | Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide. Receives: Drug: Lenvatinib; Drug: Ifosfamide; Drug: Etoposide |
| Randomization Phase: Ifosfamide + Etoposide | Active comparator | 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. Receives: Drug: Ifosfamide; Drug: Etoposide; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) by Independent Imaging Review (IIR) Assessment
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.
Measured: 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)
Secondary outcomes (11)
Percentage of Participants With PFS at Month 4 (PFS-4m Rate) by IIR Assessment
PFS rate at 4 months as assessed by IIR was defined as the percentage of participants who were alive and without PD at 4 months from the randomization date using RECIST v1.1. PD was defined as at least a 20% increase or 5 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. The PFS-4m was estimated using the Kaplan-Meier method.
Measured: Month 4
Percentage of Participants With PFS at 1 Year or Month 12 (PFS-1y Rate) by IIR Assessment
PFS-1y rate as assessed by IIR was defined as the percentage of participants who were alive and without PD at 1 year from randomization date using RECIST v1.1. PD was defined as at least a 20% increase or 5 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-1y rate was estimated using Kaplan-Meier method.
Measured: Month 12 or 1 Year
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause. The median OS was from Kaplan-Meier product-limit estimates and 2-sided 95% CIs from a generalized Brookmeyer and Crowley method.
Measured: From the date of randomization to the date of death from any cause (up to 37.1 months)
Percentage of Participants With Overall Survival at 1 Year or Month 12 (OS-1y)
OS-1y was defined as the time from the date of randomization to the date of death from any cause assessed up to 1 year. OS was calculated using the Kaplan-Meier method.
Measured: Month 12 or 1 Year
Objective Response Rate at Month 4 (ORR-4m) by IIR Assessment
ORR-4m was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) as determined by IIR using RECIST v1.1 within the first 4 months. CR: 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 to less than (<) 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 95% confidence interval (CI) of ORR was calculated using the method of Clopper and Pearson.
Measured: Month 4
ORR by IIR Assessment
ORR by IIR was defined as the percentage of participants with best overall response of CR or PR determined using RECIST v1.1. CR: 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 to <10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 95% CI of ORR was calculated using the method of Clopper and Pearson.
Measured: 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)
TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Serious adverse events (SAE) was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria.
Measured: 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
Plasma concentration of lenvatinib in participants from Treatment Arm A (Lenvatinib + Ifosfamide + Etoposide) at different time points were reported. As planned, data for this outcome measure was analyzed for treatment arm A only. Lenvatinib concentration in plasma was quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method.
Measured: 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
Health-Related Quality of Life (HRQoL): PedsQL 4.0 Generic Core Scale is a multidimensional scale. It included assessment of 4 dimensions: physical functioning (8 items), emotional functioning (8 items), social functioning (8 items), and school functioning (5 items - children greater than or equal to [>=] 5 years, adults; 3 items - toddlers [aged 2-4 years]). Each item was reported using a 5-point Likert scale, items were then reverse-scored and linearly transformed to a 0 to 100 scale. Generic Core Scale total score: sum of all the items divided by the number of items answered across all the scales. Total score ranges from 0 to 100, where higher scores=better HRQoL, lower scores=worse HRQoL.
Measured: Baseline and Month 4
Change From Baseline in PedsQL Scale: Cancer Module Scale Score at Month 4
HRQoL: PedsQL 3.0 Cancer Module Scale measured pediatric cancer-specific HRQoL. It included assessment of 8 dimensions: pain and hurt (2 items), nausea (5 items), procedural anxiety (3 items), treatment anxiety (3 items), worry (3 items), cognitive problems (3 items - toddlers [aged 2-4], 4 items - young children [aged 5-7]; 5 items for children aged >=8 years, adults), perceived physical appearance (3 items), communication (3 items). Each item was reported using a 5-point Likert scale, items were then reverse-scored and linearly transformed to a 0 to 100 scale. Cancer Module total score: sum of all items divided by the number of items answered on all the scales. Total score ranges from 0 to 100, where higher scores=better HRQoL, lower scores=worse HRQoL.
Measured: Baseline and Month 4
Number of Participants Categorized Based on Overall Palatability and Acceptability Questionnaire Responses for Suspension of Lenvatinib
The palatability and acceptability of lenvatinib oral suspension formulation was assessed using the Palatability Questionnaire. In the questionnaire, participants were asked to answer palatability and acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell, how does it feel in the mouth and overall acceptability in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. In this outcome measure, number of participants have been reported per their overall palatability and acceptability responses.
Measured: Cycle 1 Day 1 (Cycle length = 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2019
- Study start23 Mar 2020
- Primary completion22 Jun 2022
- Study completion17 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04154189
- Sponsor's protocol ID
- E7080-G000-230
- Other IDs
- 2019-003696-19, 2019
- Status last verified
- Jul 2024
- First submitted
- 1 Nov 2019
- Last updated
- 22 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
Publications
Gaspar N, Hung GY, Strauss SJ, Campbell-Hewson Q, Dela Cruz FS, Glade Bender JL, Koh KN, Whittle SB, Chan GC, Gerber NU, Palmu S, Morgenstern DA, Longhi A, Baecklund F, Lee JA, Locatelli F, Marquez Vega C, Janeway KA, McCowage G, McCabe MG, Bidadi B, Huang J, McKenzie J, Okpara CE, Bautista F; OLIE Study Investigators. Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2024 Dec 1;10(12):1645-1653. doi: 10.1001/jamaoncol.2024.4381.
PubMed 39418029Gaspar N, Venkatramani R, Hecker-Nolting S, Melcon SG, Locatelli F, Bautista F, Longhi A, Lervat C, Entz-Werle N, Casanova M, Aerts I, Strauss SJ, Thebaud E, Morland B, Nieto AC, Marec-Berard P, Gambart M, Rossig C, Okpara CE, He C, Dutta L, Campbell-Hewson Q. Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study. Lancet Oncol. 2021 Sep;22(9):1312-1321. doi: 10.1016/S1470-2045(21)00387-9. Epub 2021 Aug 17.
PubMed 34416158Gaspar N, Campbell-Hewson Q, Huang J, Okpara CE, Bautista F. OLIE, ITCC-082: a Phase II trial of lenvatinib plus ifosfamide and etoposide in relapsed/refractory osteosarcoma. Future Oncol. 2021 Nov;17(32):4249-4261. doi: 10.2217/fon-2021-0743. Epub 2021 Aug 12.
PubMed 34382412
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04154189
- Acronym / sponsor ID
- E7080-G000-230
- Conditions
- Osteosarcoma
- Keywords
- Osteosarcoma, Lenvatinib, Ifosfamide, Etoposide, E7080, Relapsed or Refractory Osteosarcoma, Pediatrics, Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 23 Mar 2020 (actual)
- Primary completion
- 22 Jun 2022 (actual)
- Study completion
- 17 Aug 2023 (actual)
- First posted
- 6 Nov 2019 (actual)
- Results
- Posted 7 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Randomization Phase: Lenvatinib + Ifosfamide + Etoposide | Experimental | Drug: Lenvatinib, Drug: Ifosfamide, Drug: EtoposideParticipants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide. |
| Randomization Phase: Ifosfamide + Etoposide | Active comparator | Drug: Ifosfamide, Drug: Etoposide, Drug: LenvatinibParticipants 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. |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- 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 (<)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
Key exclusion criteria (13 listed)
- 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 1. 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])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: E7080Lenvatinib 14 milligrams per square meter (mg/m^2) capsules will be administered once daily on Days 1 to 21 of each 21-day cycle until disease progression (PD), development of unacceptable toxicity, participant request, withdrawal of consent, or discontinuation of study by the sponsor. An extemporaneous suspension of lenvatinib capsules may be used for participants unable to swallow capsules. | Drug | Randomization Phase: Lenvatinib + Ifosfamide + Etoposide |
| IfosfamideIfosfamide 3000 milligrams per square meter per day (mg/m^2/day) intravenous infusion will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. | Drug | Randomization Phase: Ifosfamide + Etoposide, Randomization Phase: Lenvatinib + Ifosfamide + Etoposide |
| EtoposideEtoposide 100 mg/m^2/day intravenous infusion will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. | Drug | Randomization Phase: Ifosfamide + Etoposide, Randomization Phase: Lenvatinib + Ifosfamide + Etoposide |
| LenvatinibAlso: E7080Lenvatinib 14 mg/m^2 capsules will be administered once daily on Days 1 to 21 of each 21-day cycle until the next PD (per response evaluation criteria in solid tumors [RECIST] 1.1 as assessed by investigator), development of unacceptable toxicity, participant request, or withdrawal of consent, whichever occurs first. | Drug | Randomization Phase: Ifosfamide + Etoposide |
Primary outcome
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.
11 secondary outcomes
Percentage of Participants With PFS at Month 4 (PFS-4m Rate) by IIR Assessment
Time frame: Month 4
Percentage of Participants With PFS at 1 Year or Month 12 (PFS-1y Rate) by IIR Assessment
Time frame: Month 12 or 1 Year
Overall Survival (OS)
Time frame: From the date of randomization to the date of death from any cause (up to 37.1 months)
Percentage of Participants With Overall Survival at 1 Year or Month 12 (OS-1y)
Time frame: Month 12 or 1 Year
Objective Response Rate at Month 4 (ORR-4m) by IIR Assessment
Time frame: Month 4
ORR by IIR Assessment
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: Baseline and Month 4
Change From Baseline in PedsQL Scale: Cancer Module Scale Score at Month 4
Time frame: Baseline and Month 4
Number of Participants Categorized Based on Overall Palatability and Acceptability Questionnaire Responses for Suspension of Lenvatinib
Time frame: Cycle 1 Day 1 (Cycle length = 21 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39418029Gaspar N, Hung GY, Strauss SJ, Campbell-Hewson Q, Dela Cruz FS, Glade Bender JL, Koh KN, Whittle SB, Chan GC, Gerber NU, Palmu S, Morgenstern DA, Longhi A, Baecklund F, Lee JA, Locatelli F, Marquez Vega C, Janeway KA, McCowage G, McCabe MG, Bidadi B, Huang J, McKenzie J, Okpara CE, Bautista F; OLIE Study Investigators. Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2024 Dec 1;10(12):1645-1653. doi: 10.1001/jamaoncol.2024.4381.
- Derived from this study: PubMed 34416158Gaspar N, Venkatramani R, Hecker-Nolting S, Melcon SG, Locatelli F, Bautista F, Longhi A, Lervat C, Entz-Werle N, Casanova M, Aerts I, Strauss SJ, Thebaud E, Morland B, Nieto AC, Marec-Berard P, Gambart M, Rossig C, Okpara CE, He C, Dutta L, Campbell-Hewson Q. Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study. Lancet Oncol. 2021 Sep;22(9):1312-1321. doi: 10.1016/S1470-2045(21)00387-9. Epub 2021 Aug 17.
- Derived from this study: PubMed 34382412Gaspar N, Campbell-Hewson Q, Huang J, Okpara CE, Bautista F. OLIE, ITCC-082: a Phase II trial of lenvatinib plus ifosfamide and etoposide in relapsed/refractory osteosarcoma. Future Oncol. 2021 Nov;17(32):4249-4261. doi: 10.2217/fon-2021-0743. Epub 2021 Aug 12.
- Individual participant dataSharing planned: Yes. Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
84 sites in 21 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenvatinib, Ifosfamide and Etoposide in people with Osteosarcoma, run by Eisai Inc. at 84 sites in 21 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 84 sites in United States, France, United Kingdom, Spain, Australia and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04154189, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2024.