A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720)
24 de julio de 2018 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
219
Fase
- Fase 2
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
4 años y mayores (Niño, Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: 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.
|
Robatumumab IV every two weeks until disease progression.
Otros nombres:
|
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Experimental: 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.
Otros nombres:
|
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Experimental: 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.
Otros nombres:
|
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Experimental: 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.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)
Periodo de tiempo: 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.
|
Up to 1 year following the start of study therapy
|
|
Number of Participants With >= 25% Change in Tumor Proliferation After Exposure to Robatumumab (Group 1 Only)
Periodo de tiempo: 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)
Periodo de tiempo: 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.
|
Up to 1 year following the start of study therapy
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Overall Survival
Periodo de tiempo: 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)
|
|
Time Until Tumor Relapse (Group 1 Only)
Periodo de tiempo: 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)
|
|
Area Under the Concentration-time Curve (AUC) of Serum Levels of Robatumumab (Group 1 Only)
Periodo de tiempo: 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)
|
|
|
Incidence of Anti-robatumumab Antibodies
Periodo de tiempo: 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.
|
Up to 2 years
|
|
Number of Participants Experiencing Treatment-Emergent Adverse Events
Periodo de tiempo: 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.
|
Up to 2 years
|
|
Time to Disease Progression (Groups 2 and 3 Only)
Periodo de tiempo: 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)
|
|
Overall Survival (Groups 2 and 3 Only)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de febrero de 2008
Finalización primaria (Actual)
31 de agosto de 2011
Finalización del estudio (Actual)
31 de agosto de 2013
Fechas de registro del estudio
Enviado por primera vez
17 de enero de 2008
Primero enviado que cumplió con los criterios de control de calidad
6 de febrero de 2008
Publicado por primera vez (Estimar)
18 de febrero de 2008
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
23 de agosto de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
24 de julio de 2018
Última verificación
1 de julio de 2018
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias De Tejidos Conectivos Y Blandos
- Neoplasias por tipo histológico
- Neoplasias
- Neoplasias Glandulares y Epiteliales
- Neoplasias Neuroepiteliales
- Neoplasias De Células Germinales Y Embrionarias
- Neoplasias De Tejido Nervioso
- Neoplasias De Tejido Óseo
- Neoplasias Del Tejido Conectivo
- Sarcoma
- Sarcoma de Ewing
- Osteosarcoma
- Tumores neuroectodérmicos
- Tumores Neuroectodérmicos Primitivos
- Tumores Neuroectodérmicos Primitivos Periféricos
- Efectos fisiológicos de las drogas
- Factores inmunológicos
- Anticuerpos Monoclonales
Otros números de identificación del estudio
- P04720
Plan de datos de participantes individuales (IPD)
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SÍ
Descripción del plan IPD
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Datos del estudio/Documentos
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .