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

Phase 2TerminatedNCT00617890

Merck Sharp & Dohme LLC219 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Eligibility

Sex: ALLMin age: 4 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 1 year following the start of study therapy

Secondary Outcomes

Overall Survival

This is a measure of the number of participants known to be alive at the time of data analysis for this study.

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

Time Until Tumor Relapse (Group 1 Only)

This is a measure of the time from the start of the study to documented relapse of disease.

Time frame: 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)

Time frame: 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

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.

Time frame: Up to 2 years

Number of Participants Experiencing Treatment-Emergent Adverse Events

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.

Time frame: Up to 2 years

Time to Disease Progression (Groups 2 and 3 Only)

This is a measure of the time from the start of the study to the time of documented disease progression.

Time frame: 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)

This is a measure of the time of survival from first dose to documentation of death

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

Duration of Response (Groups 2 and 3 Only)

This is a measure of the amount of time in which the tumor responded to therapy.

Time frame: From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)