Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been terminated.
(The study was prematurely terminated for strategic reasons, not for a safety concern.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00617890
First received: January 17, 2008
Last updated: July 19, 2016
Last verified: July 2016
Results First Received: November 9, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Osteosarcoma
Sarcoma, Ewing's
Peripheral Neuroectodermal Tumor
Intervention: Biological: robatumumab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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 1: 10 mg/kg Participants 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 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 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's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.

Participant Flow:   Overall Study
    Group 1: 0.3 mg/kg     Group 1: 10 mg/kg     Group 2: 10 mg/kg     Group 3: 10 mg/kg  
STARTED     35     33     35     116  
Received Treatment     34     33     34     115  
COMPLETED     4     5     0     1  
NOT COMPLETED     31     28     35     115  
Treatment ongoing at data cut-off                 0                 0                 0                 5  
Lack of Efficacy                 23                 26                 30                 97  
Lost to Follow-up                 0                 0                 1                 2  
Withdrawal by Subject                 4                 1                 0                 2  
Protocol Violation                 2                 1                 0                 0  
Adverse Event                 1                 0                 3                 8  
Not treated                 1                 0                 1                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Three participants did not receive study treatment but are included in the baseline population.

Reporting Groups
  Description
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 1: 10 mg/kg Participants 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 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 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's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Total Total of all reporting groups

Baseline Measures
    Group 1: 0.3 mg/kg     Group 1: 10 mg/kg     Group 2: 10 mg/kg     Group 3: 10 mg/kg     Total  
Number of Participants  
[units: participants]
  35     33     35     116     219  
Age  
[units: Years]
Mean (Standard Deviation)
  23.7  (15.5)     20.1  (10.3)     27.5  (15.3)     24.6  (11.4)     24.3  (12.8)  
Gender  
[units: Participants]
         
Female     14     13     11     43     81  
Male     21     20     24     73     138  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)   [ Time Frame: Up to 1 year following the start of study therapy ]

2.  Primary:   Number of Participants With >= 25% Change in Tumor Proliferation After Exposure to Robatumumab (Group 1 Only)   [ Time Frame: Approximately 14 days ]

3.  Primary:   Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only)   [ Time Frame: Up to 1 year following the start of study therapy ]

4.  Secondary:   Overall Survival   [ Time Frame: From start of treatment until death or data analysis cut off (Up to 3.4 years) ]

5.  Secondary:   Time Until Tumor Relapse (Group 1 Only)   [ Time Frame: From start of treatment until relapse or data analysis cut off (Up to 3.4 years) ]

6.  Secondary:   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) ]

7.  Secondary:   Incidence of Anti-robatumumab Antibodies   [ Time Frame: Up to 2 years ]

8.  Secondary:   Number of Participants Experiencing Treatment-Emergent Adverse Events   [ Time Frame: Up to 2 years ]

9.  Secondary:   Time to Disease Progression (Groups 2 and 3 Only)   [ Time Frame: From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years) ]

10.  Secondary:   Overall Survival (Groups 2 and 3 Only)   [ Time Frame: From start of treatment until death or data analysis cut off (Up to 3.4 years) ]

11.  Secondary:   Duration of Response (Groups 2 and 3 Only)   [ Time Frame: From time of documented response until disease progression or data analysis cut off (Up to 3.4 years) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was stopped prematurely for administrative reasons; not all planned endpoints were analyzed.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00617890     History of Changes
Other Study ID Numbers: P04720
Study First Received: January 17, 2008
Results First Received: November 9, 2015
Last Updated: July 19, 2016
Health Authority: United States: Food and Drug Administration