A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720)
24. července 2018 aktualizováno: Merck Sharp & Dohme LLC
A Study to Determine the Activity of SCH 717454 in Subjects With Osteosarcoma or Ewing's Sarcoma That Has Relapsed After Standard Systemic Therapy
Participants with relapsed osteosarcoma that can be treated with surgery will be randomized to robatumumab administered intravenously (IV) at one of two dose levels. These participants will first receive robatumumab, have surgery performed, and continue to receive treatment every two weeks until a year of dosing, or until disease progression.
Participants with unresectable osteosarcoma or Ewing Sarcoma will receive robatumumab IV once every two weeks until disease progression. Participants who achieve a complete response (CR) or partial response (PR) after tumor evaluations may undergo surgical resection. After surgery, participants are eligible to receive 10 mg/kg robatumumab until disease recurrence/progression or one year of total dosing, whichever occurs first.
Přehled studie
Postavení
Ukončeno
Intervence / Léčba
Detailní popis
Participants with resectable osteosarcoma will be randomized to one of two dose levels of robatumumab to be given intravenously. These participants will first receive robatumumab according to randomized treatment, and have surgery performed 10 to 14 days after initial dosing. Participants will be allowed to recover from surgery four to six weeks prior to additional robatumumab administration at their randomized dose level. robatumumab will then be administered on the same calendar day once every two weeks. Participants will continue to receive robatumumab until disease recurrence, or until completing a year of dosing at the same dose level assigned, whichever occurs first.
Participants with unresectable osteosarcoma or Ewing Sarcoma will be assigned treatment to robatumumab IV administered once every two weeks and will continue to receive robatumumab until disease progression. Participants who achieve a CR or PR after tumor evaluations may undergo surgical resection. After surgery, participants are eligible to receive 10 mg/kg robatumumab until disease recurrence/progression or one year of total dosing, whichever occurs first.
Typ studie
Intervenční
Zápis (Aktuální)
219
Fáze
- Fáze 2
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
4 roky a starší (Dítě, Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- A participant must be 11 years of age or older and may be of any race, and gender; participants between 4 and 10 years of age, inclusive, may be considered on a site-by-site basis.
- A participant must have a diagnosis of histologically confirmed osteosarcoma or Ewing sarcoma;
A participant with either:
- relapsed and resectable osteosarcoma
- relapsed and unresectable osteosarcoma that is refractory to standard therapy, ie. has relapsed after prior systemic treatment with active chemotherapy agents
- Ewing sarcoma that is refractory to standard systemic therapies
- A participant >16 years of age must have an Eastern Cooperative Oncology Group (ECOG) performance status of <=2; a participant <=16 years of age must have a Karnofsky performance status between 50% and 100% or a Lansky play scale between 50% and 100%
- A participant must have adequate organ function.
Exclusion Criteria:
- A participant with a history of another malignancy (with the exception of non-melanoma skin cancer or carcinoma in situ of the cervix treated with curative intent at least 2 years prior to start of treatment, or other adequately treated malignancy for which the subject has been disease free for >=5 years)
- A participant who has known treated or untreated leptomeningeal metastasis, or a metastatic central nervous system lesion
- A participant with a history of uncontrolled diabetes mellitus
- A participant with a recent myocardial infarction (within the past year); or a participant who at the time of Screening presents with unstable or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality
- A participant with an active infection
- A participant with clinically significant hepatitis at Screening, or a participant who is hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive
- A participant who has been treated with an anti-insulin-like growth factor receptor 1 (anti-IGF-1R)- targeted drug or antibody
- A participant with known hypersensitivity to other antibodies, or any accompanying excipients associated with these medications.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Group 1: 0.3 mg/kg
Participants received robatumumab 0.3 mg/kg intravenously (IV) as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 0.3 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing.
This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.
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Robatumumab IV every two weeks until disease progression.
Ostatní jména:
|
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Experimentální: Group 1: 10 mg/kg
Participants who received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing.
This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.
|
Robatumumab IV every two weeks until disease progression.
Ostatní jména:
|
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Experimentální: Group 2: 10 mg/kg
Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing.
This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.
|
Robatumumab IV every two weeks until disease progression.
Ostatní jména:
|
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Experimentální: Group 3: 10 mg/kg
Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing.
This group comprised participants with Ewing sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
|
Robatumumab IV every two weeks until disease progression.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)
Časové okno: Up to 1 year following the start of study therapy
|
This is a measure of the number of participants with a complete response (CR) or partial response (PR) to therapy, confirmed by central review.
Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.
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Up to 1 year following the start of study therapy
|
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Number of Participants With >= 25% Change in Tumor Proliferation After Exposure to Robatumumab (Group 1 Only)
Časové okno: Approximately 14 days
|
Tumor proliferation was measured using Ki-67 levels.
Ki-67 is nuclear protein associated with cellular proliferation.
|
Approximately 14 days
|
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Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only)
Časové okno: Up to 1 year following the start of study therapy
|
Responses to treatment (complete response, partial response, or stable disease) confirmed by central review for Participants in Group 2. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.
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Up to 1 year following the start of study therapy
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall Survival
Časové okno: From start of treatment until death or data analysis cut off (Up to 3.4 years)
|
This is a measure of the number of participants known to be alive at the time of data analysis for this study.
|
From start of treatment until death or data analysis cut off (Up to 3.4 years)
|
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Time Until Tumor Relapse (Group 1 Only)
Časové okno: From start of treatment until relapse or data analysis cut off (Up to 3.4 years)
|
This is a measure of the time from the start of the study to documented relapse of disease.
|
From start of treatment until relapse or data analysis cut off (Up to 3.4 years)
|
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Area Under the Concentration-time Curve (AUC) of Serum Levels of Robatumumab (Group 1 Only)
Časové okno: End of infusion on Day 1, and then prior to surgery, before and after the 2nd, 3rd, and 8th doses (up to 20 weeks)
|
End of infusion on Day 1, and then prior to surgery, before and after the 2nd, 3rd, and 8th doses (up to 20 weeks)
|
|
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Incidence of Anti-robatumumab Antibodies
Časové okno: Up to 2 years
|
For biological agents, it is possible for the host (participant) to develop antibodies to the agent.
This outcome measure was planned to find out the number of participants who developed the antibodies after treatment with robatumumab.
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Up to 2 years
|
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Number of Participants Experiencing Treatment-Emergent Adverse Events
Časové okno: Up to 2 years
|
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Treatment-emergent adverse events are those that occur after participants have received study treatment, or existing adverse events that occurred during screening that increase in severity after study treatment.
Adverse events in the Group 1: 0.3 mg/kg arm that occurred after switching to the 10 mg/kg dose are displayed under the originally assigned treatment.
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Up to 2 years
|
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Time to Disease Progression (Groups 2 and 3 Only)
Časové okno: From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years)
|
This is a measure of the time from the start of the study to the time of documented disease progression.
|
From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years)
|
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Overall Survival (Groups 2 and 3 Only)
Časové okno: From start of treatment until death or data analysis cut off (Up to 3.4 years)
|
This is a measure of the time of survival from first dose to documentation of death
|
From start of treatment until death or data analysis cut off (Up to 3.4 years)
|
|
Duration of Response (Groups 2 and 3 Only)
Časové okno: From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)
|
This is a measure of the amount of time in which the tumor responded to therapy.
|
From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- Asmane I, Watkin E, Alberti L, Duc A, Marec-Berard P, Ray-Coquard I, Cassier P, Decouvelaere AV, Ranchere D, Kurtz JE, Bergerat JP, Blay JY. Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas. Eur J Cancer. 2012 Nov;48(16):3027-35. doi: 10.1016/j.ejca.2012.05.009. Epub 2012 Jun 7.
- Anderson PM, Bielack SS, Gorlick RG, Skubitz K, Daw NC, Herzog CE, Monge OR, Lassaletta A, Boldrini E, Papai Z, Rubino J, Pathiraja K, Hille DA, Ayers M, Yao SL, Nebozhyn M, Lu B, Mauro D. A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma. Pediatr Blood Cancer. 2016 Oct;63(10):1761-70. doi: 10.1002/pbc.26087. Epub 2016 Jun 30.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
1. února 2008
Primární dokončení (Aktuální)
31. srpna 2011
Dokončení studie (Aktuální)
31. srpna 2013
Termíny zápisu do studia
První předloženo
17. ledna 2008
První předloženo, které splnilo kritéria kontroly kvality
6. února 2008
První zveřejněno (Odhad)
18. února 2008
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
23. srpna 2018
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
24. července 2018
Naposledy ověřeno
1. července 2018
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Novotvary, pojivové a měkké tkáně
- Novotvary podle histologického typu
- Novotvary
- Novotvary, žlázové a epiteliální
- Novotvary, neuroepiteliální
- Novotvary, zárodečné buňky a embryonální
- Novotvary, nervová tkáň
- Novotvary, kostní tkáň
- Novotvary, pojivová tkáň
- Sarkom
- Sarkom, Ewing
- Osteosarkom
- Neuroektodermální nádory
- Neuroektodermální nádory, primitivní
- Neuroektodermální nádory, primitivní, periferní
- Fyziologické účinky léků
- Imunologické faktory
- Monoklonální protilátky
Další identifikační čísla studie
- P04720
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu IPD
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Studijní data/dokumenty
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
Klinické studie na robatumumab
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