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

NCT00617890 | Terminated Phase 2 Results

• 1 other identifier: P04720
• Study Type: interventional
• Target: 219
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Osteosarcoma; Sarcoma, Ewing's; Peripheral Neuroectodermal Tumor

Keywords

anti-IGF-1R

Outcome Measures

Primary Outcomes (3)

• Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)

  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)

  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)

  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

Secondary Outcomes (8)

• Overall Survival

  From start of treatment until death or data analysis cut off (Up to 3.4 years)

• Time Until Tumor Relapse (Group 1 Only)

  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)

  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

  Up to 2 years

• Number of Participants Experiencing Treatment-Emergent Adverse Events

  Up to 2 years

Study Arms (4)

Group 1: 0.3 mg/kg

EXPERIMENTAL

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.

Biological: robatumumab

Group 1: 10 mg/kg

EXPERIMENTAL

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.

Biological: robatumumab

Group 2: 10 mg/kg

EXPERIMENTAL

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.

Biological: robatumumab

Group 3: 10 mg/kg

EXPERIMENTAL

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.

Biological: robatumumab

Interventions

robatumumab BIOLOGICAL

Robatumumab IV every two weeks until disease progression.

Also known as: SCH 717454, SCH 717454 (19D12), MK-7454

Group 1: 0.3 mg/kg; Group 1: 10 mg/kg; Group 2: 10 mg/kg; Group 3: 10 mg/kg

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• 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.

  PMID: 27362300 RESULT

• 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.

  PMID: 22682017 DERIVED

MeSH Terms

Conditions

Osteosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral

Interventions

robatumumab

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Limitations and Caveats

The study was stopped prematurely for administrative reasons; not all planned endpoints were analyzed.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: February 18, 2008
• Study Start: February 1, 2008
• Primary Completion: August 31, 2011
• Study Completion: August 31, 2013
• Last Updated: August 23, 2018
• Results First Posted: December 11, 2015

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share