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
NCT ID: NCT04154189
Last Updated: 2024-07-22
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
81 participants
INTERVENTIONAL
2020-03-23
2023-08-17
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Randomization Phase: Lenvatinib + Ifosfamide + Etoposide
Participants with relapsed or refractory osteosarcoma will receive lenvatinib in combination with ifosfamide and etoposide.
Lenvatinib
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.
Ifosfamide
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.
Etoposide
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.
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.
Ifosfamide
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.
Etoposide
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.
Lenvatinib
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.
Interventions
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Lenvatinib
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.
Ifosfamide
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.
Etoposide
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.
Lenvatinib
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Refractory or relapsed osteosarcoma after 1 to 2 prior lines of 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 able to perform activities of daily living while wheelchair bound, 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 or multigated acquisition (MUGA) scan
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. 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
10. Must have no prior history of lenvatinib treatment
Eligibility for optional lenvatinib crossover:
1. Disease progression per RECIST 1.1 (as confirmed by IIR for all participants who crossover prior to the study data-cut)
2. No new systemic anti-cancer medication administered after the last dose of study drugs
4. Study is ongoing
Exclusion Criteria
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 corrected QT (QTc) interval (example, a repeated demonstration of a QTc interval greater than \[\>\] 480 millisecond \[msec\])
6. 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
7. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib
8. Pre-existing Grade \>=3 gastrointestinal or non-gastrointestinal fistula
9. 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
10. 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
11. History of ifosfamide-related Grade \>=3 nephrotoxicity or encephalopathy
12. Known to be human immunodeficiency virus (HIV) positive
13. 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
2 Years
25 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Eisai Inc.
INDUSTRY
Responsible Party
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Locations
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Children's of Alabama
Birmingham, Alabama, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Children's Hospital of Orange County
Orange, California, United States
UCSF Benioff Children's Hospitals
San Francisco, California, United States
Childrens Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Riley Hospital For Children
Indianapolis, Indiana, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Children's Medical Center Dallas
Dallas, Texas, United States
Cook Children's Health Care System
Fort Worth, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
Chris O'Brien Lifehouse Hospital
Camperdown, , Australia
Perth Childrens Hospital
Nedlands, , Australia
Royal Children's Hospital Melbourne
Parkville, , Australia
Queensland Children's Hospital
South Brisbane, , Australia
Children's Hospital at Westmead
Westmead, , Australia
St. Anna Kinderspital
Vienna, , Austria
UZ Gent
Ghent, , Belgium
Hospital For Sick Children
Toronto, , Canada
FN Brno 2 Detska Klinika
Brno, , Czechia
Fakultní nemocnice v Motole
Prague, , Czechia
Tampereen yliopistollinen sairaala
Tampere, Länsi-Suomen Lääni, Finland
Centre Hospitalier Universitaire de Bordeaux, Hopital Pellegrin
Bordeaux, , France
Centre Oscar Lambret
Lille, , France
Centre Léon Berard
Lyon, , France
Hopitaux de La Timone
Marseille, , France
Hôpital de La Mère Et de L'enfant
Nantes, , France
CHU de Nice
Nice, , France
Hôpital Armand Trousseau
Paris, , France
Institut Curie
Paris, , France
Hopital de Hautepierre
Strasbourg, , France
Hôpital Des Enfants
Toulouse, , France
CHRU Nancy
Vandœuvre-lès-Nancy, , France
Institut Gustave Roussy
Villejuif, , France
Hong Kong Children's Hospital
Hong Kong, , Hong Kong
Prince of Wales Hospital
Hong Kong, , Hong Kong
Children's Health Ireland at Crumlin
Dublin, , Ireland
Schneider Children's Medical Center of Israel
Petah Tikva, , Israel
Istituti Ortopedici Rizzoli
Bologna, , Italy
Azienda Ospedaliera A Meyer
Florence, , Italy
Istituto Giannina Gaslini
Genova, , Italy
Istituto Nazionale Dei Tumori
Milan, , Italy
IRCCS Ospedale Pediatrico Bambino Gesù
Roma, , Italy
Princess Maxima Center for Pediatric Oncology
Utrecht, , Netherlands
Auckland City Hospital
Auckland, , New Zealand
Starship Children's Hospital
Auckland, , New Zealand
KK Women's and Children's Hospital
Singapore, , Singapore
National Cancer Centre
Singapore, , Singapore
National University Hospital
Singapore, , Singapore
National Cancer Center
Goyang-si, , South Korea
Asan Medical Center
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital Yonsei University Health System
Seoul, , South Korea
Hospital Universitario de Cruces
Barakaldo, , Spain
Hospital Sant Joan de Deu
Barcelona, , Spain
Hospital Universitario Vall d'Hebrón
Barcelona, , Spain
Hospital Infantil Universitario Niño Jesus
Madrid, , Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, , Spain
Drottning Silvias Barn Och Ungdomssjukhus
Gothenburg, , Sweden
Skanes Universitetssjukhus Lund
Lund, , Sweden
Karolinska Universitetssjukhuset Solna
Stockholm, , Sweden
Centre Hospitalier Universitaire Vaudois
Lausanne, , Switzerland
Kinderspital Zürich - Eleonorenstiftung
Zurich, , Switzerland
National Taiwan University Hospital
Taipei, , Taiwan
Taipei Veterans General Hospital
Taipei, , Taiwan
Birmingham Children's Hospital
Birmingham, , United Kingdom
The Royal Hospital for Children
Bristol, , United Kingdom
Royal Hospital for Children
Glasgow, , United Kingdom
Leeds Children Hospital
Leeds, , United Kingdom
Alder Hey Children's Hospital
Liverpool, , United Kingdom
UCL Cancer Institute
London, , United Kingdom
Royal Manchester Childrens Hospital
Manchester, , United Kingdom
The Christie NHS Foundation Trust
Manchester, , United Kingdom
Royal Victoria Infirmary
Newcastle, , United Kingdom
John Radcliffe Hospital
Oxford, , United Kingdom
Countries
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References
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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.
Gaspar 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.
Gaspar 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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2019-003696-19
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
E7080-G000-230
Identifier Type: -
Identifier Source: org_study_id
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