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

NCT ID: NCT00617890

Last Updated: 2018-08-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-01
• Study Completion Date: 2013-08-31

Brief Summary

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.

Detailed Description

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.

Conditions

Osteosarcoma; Sarcoma, Ewing's; Peripheral Neuroectodermal Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

robatumumab

Intervention Type: BIOLOGICAL

Robatumumab IV every two weeks until disease progression.

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.

Group Type: EXPERIMENTAL

robatumumab

Intervention Type: BIOLOGICAL

Robatumumab IV every two weeks until disease progression.

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.

Group Type: EXPERIMENTAL

robatumumab

Intervention Type: BIOLOGICAL

Robatumumab IV every two weeks until disease progression.

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.

Group Type: EXPERIMENTAL

robatumumab

Intervention Type: BIOLOGICAL

Robatumumab IV every two weeks until disease progression.

Interventions

robatumumab

Robatumumab IV every two weeks until disease progression.

Intervention Type: BIOLOGICAL

Other Intervention Names

SCH 717454; SCH 717454 (19D12); MK-7454

Eligibility Criteria

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.

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 27362300 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22682017 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

P04720

Identifier Type: -

Identifier Source: org_study_id