A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720)
2018. július 24. frissítette: 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.
A tanulmány áttekintése
Állapot
Megszűnt
Beavatkozás / kezelés
Részletes leírás
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.
Tanulmány típusa
Beavatkozó
Beiratkozás (Tényleges)
219
Fázis
- 2. fázis
Részvételi kritériumok
A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.
Jogosultsági kritériumok
Tanulmányozható életkorok
4 év és régebbi (Gyermek, Felnőtt, Idősebb felnőtt)
Egészséges önkénteseket fogad
Nem
Tanulmányozható nemek
Összes
Leírás
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.
Tanulási terv
Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Kettős
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
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Kísérleti: 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.
Más nevek:
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Kísérleti: 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.
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Robatumumab IV every two weeks until disease progression.
Más nevek:
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Kísérleti: 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.
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Robatumumab IV every two weeks until disease progression.
Más nevek:
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Kísérleti: 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.
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Robatumumab IV every two weeks until disease progression.
Más nevek:
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)
Időkeret: Up to 1 year following the start of study therapy
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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)
Időkeret: Approximately 14 days
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Tumor proliferation was measured using Ki-67 levels.
Ki-67 is nuclear protein associated with cellular proliferation.
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Approximately 14 days
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Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only)
Időkeret: Up to 1 year following the start of study therapy
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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
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Overall Survival
Időkeret: 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.
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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)
Időkeret: From start of treatment until relapse or data analysis cut off (Up to 3.4 years)
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This is a measure of the time from the start of the study to documented relapse of disease.
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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)
Időkeret: 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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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
Időkeret: Up to 2 years
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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
Időkeret: Up to 2 years
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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)
Időkeret: From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years)
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This is a measure of the time from the start of the study to the time of documented disease progression.
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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)
Időkeret: From start of treatment until death or data analysis cut off (Up to 3.4 years)
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This is a measure of the time of survival from first dose to documentation of death
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From start of treatment until death or data analysis cut off (Up to 3.4 years)
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Duration of Response (Groups 2 and 3 Only)
Időkeret: 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.
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From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)
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Együttműködők és nyomozók
Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.
Szponzor
Publikációk és hasznos linkek
A vizsgálattal kapcsolatos információk beviteléért felelős személy önkéntesen bocsátja rendelkezésre ezeket a kiadványokat. Ezek bármiről szólhatnak, ami a tanulmányhoz kapcsolódik.
Általános kiadványok
- 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.
Tanulmányi rekorddátumok
Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
2008. február 1.
Elsődleges befejezés (Tényleges)
2011. augusztus 31.
A tanulmány befejezése (Tényleges)
2013. augusztus 31.
Tanulmányi regisztráció dátumai
Először benyújtva
2008. január 17.
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
2008. február 6.
Első közzététel (Becslés)
2008. február 18.
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
2018. augusztus 23.
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
2018. július 24.
Utolsó ellenőrzés
2018. július 1.
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
- Neoplazmák, kötő- és lágyszövetek
- Neoplazmák szövettani típus szerint
- Neoplazmák
- Neoplazmák, mirigyes és epiteliális
- Neoplazmák, neuroepiteliális
- Neoplazmák, csírasejt és embrionális
- Neoplazmák, idegszövet
- Neoplazmák, csontszövet
- Neoplazmák, kötőszövet
- Szarkóma
- Szarkóma, Ewing
- Osteosarcoma
- Neuroektodermális daganatok
- Neuroektodermális daganatok, primitív
- Neuroektodermális daganatok, primitív, perifériás
- A gyógyszerek élettani hatásai
- Immunológiai tényezők
- Antitestek, monoklonális
Egyéb vizsgálati azonosító számok
- P04720
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
IGEN
IPD terv leírása
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Tanulmányi adatok/dokumentumok
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .