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 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
219
Fas
- Fas 2
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
4 år och äldre (Barn, Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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.
Andra namn:
|
|
Experimentell: 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.
Andra namn:
|
|
Experimentell: 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.
Andra namn:
|
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Experimentell: 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.
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Overall Survival
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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)
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
1 februari 2008
Primärt slutförande (Faktisk)
31 augusti 2011
Avslutad studie (Faktisk)
31 augusti 2013
Studieregistreringsdatum
Först inskickad
17 januari 2008
Först inskickad som uppfyllde QC-kriterierna
6 februari 2008
Första postat (Uppskatta)
18 februari 2008
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
23 augusti 2018
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
24 juli 2018
Senast verifierad
1 juli 2018
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Neoplasmer, bindväv och mjukvävnad
- Neoplasmer efter histologisk typ
- Neoplasmer
- Neoplasmer, körtel och epitel
- Neoplasmer, neuroepitelial
- Neoplasmer, könsceller och embryonala
- Neoplasmer, nervvävnad
- Neoplasmer, benvävnad
- Neoplasmer, bindväv
- Sarkom
- Sarkom, Ewing
- Osteosarkom
- Neuroektodermala tumörer
- Neuroektodermala tumörer, primitiva
- Neuroektodermala tumörer, primitiva, perifera
- Läkemedels fysiologiska effekter
- Immunologiska faktorer
- Antikroppar, monoklonala
Andra studie-ID-nummer
- P04720
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
JA
IPD-planbeskrivning
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Studiedata/dokument
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