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A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720)

24 juli 2018 bijgewerkt door: 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.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

219

Fase

  • Fase 2

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

4 jaar en ouder (Kind, Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Dubbele

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Biologisch: robatumumab
Robatumumab IV every two weeks until disease progression.
Andere namen:
  • SCH 717454
  • SCH 717454 (19D12)
  • MK-7454
Experimenteel: 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.
Biologisch: robatumumab
Robatumumab IV every two weeks until disease progression.
Andere namen:
  • SCH 717454
  • SCH 717454 (19D12)
  • MK-7454
Experimenteel: 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.
Biologisch: robatumumab
Robatumumab IV every two weeks until disease progression.
Andere namen:
  • SCH 717454
  • SCH 717454 (19D12)
  • MK-7454
Experimenteel: 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.
Biologisch: robatumumab
Robatumumab IV every two weeks until disease progression.
Andere namen:
  • SCH 717454
  • SCH 717454 (19D12)
  • MK-7454

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)
Tijdsspanne: 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)
Tijdsspanne: Approximately 14 days
Tumor proliferation was measured using Ki-67 levels. Ki-67 is nuclear protein associated with cellular proliferation.
Approximately 14 days
Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only)
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Survival
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Merck Sharp & Dohme LLC

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 februari 2008

Primaire voltooiing (Werkelijk)

31 augustus 2011

Studie voltooiing (Werkelijk)

31 augustus 2013

Studieregistratiedata

Eerst ingediend

17 januari 2008

Eerst ingediend dat voldeed aan de QC-criteria

6 februari 2008

Eerst geplaatst (Schatting)

18 februari 2008

Updates van studierecords

Laatste update geplaatst (Werkelijk)

23 augustus 2018

Laatste update ingediend die voldeed aan QC-criteria

24 juli 2018

Laatst geverifieerd

1 juli 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • P04720

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Bestudeer gegevens/documenten

  1. MVO-synopsis

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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