Clinical trial NCT00617890: A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720)
Official title: A Study to Determine the Activity of SCH 717454 in Subjects With Osteosarcoma or Ewing's Sarcoma That Has Relapsed After Standard Systemic Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteosarcoma
Sarcoma, Ewing's
Peripheral Neuroectodermal Tumor
Keywords: anti-IGF-1R
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-02-18
Enrollment: 219
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)
timeFrame: Up to 1 year following the start of study therapy
measure: Number of Participants With >= 25% Change in Tumor Proliferation After Exposure to Robatumumab (Group 1 Only)
timeFrame: Approximately 14 days
measure: Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only)
timeFrame: Up to 1 year following the start of study therapy
Secondary outcomes:
measure: Overall Survival
timeFrame: From start of treatment until death or data analysis cut off (Up to 3.4 years)
measure: Time Until Tumor Relapse (Group 1 Only)
timeFrame: From start of treatment until relapse or data analysis cut off (Up to 3.4 years)
measure: Area Under the Concentration-time Curve (AUC) of Serum Levels of Robatumumab (Group 1 Only)
timeFrame: End of infusion on Day 1, and then prior to surgery, before and after the 2nd, 3rd, and 8th doses (up to 20 weeks)
measure: Incidence of Anti-robatumumab Antibodies
timeFrame: Up to 2 years
measure: Number of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: Up to 2 years
measure: Time to Disease Progression (Groups 2 and 3 Only)
timeFrame: From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years)
measure: Overall Survival (Groups 2 and 3 Only)
timeFrame: From start of treatment until death or data analysis cut off (Up to 3.4 years)
measure: Duration of Response (Groups 2 and 3 Only)
timeFrame: From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.