A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Terminated
CT.gov ID
NCT00617890
Collaborator
(none)
219
4
67
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
219 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Feb 1, 2008
Actual Primary Completion Date
:
Aug 31, 2011
Actual Study Completion Date
:
Aug 31, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Biological: robatumumab
Robatumumab IV every two weeks until disease progression.
Other Names:
|
| Experimental: 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. |
Biological: robatumumab
Robatumumab IV every two weeks until disease progression.
Other Names:
|
| Experimental: 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. |
Biological: robatumumab
Robatumumab IV every two weeks until disease progression.
Other Names:
|
| Experimental: 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. |
Biological: robatumumab
Robatumumab IV every two weeks until disease progression.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only) [Up to 1 year following the start of study therapy]
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.
- Number of Participants With >= 25% Change in Tumor Proliferation After Exposure to Robatumumab (Group 1 Only) [Approximately 14 days]
Tumor proliferation was measured using Ki-67 levels. Ki-67 is nuclear protein associated with cellular proliferation.
- Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only) [Up to 1 year following the start of study therapy]
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.
Secondary Outcome Measures
- Overall Survival [From start of treatment until death or data analysis cut off (Up to 3.4 years)]
This is a measure of the number of participants known to be alive at the time of data analysis for this study.
- Time Until Tumor Relapse (Group 1 Only) [From start of treatment until relapse or data analysis cut off (Up to 3.4 years)]
This is a measure of the time from the start of the study to documented relapse of disease.
- 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]
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.
- Number of Participants Experiencing Treatment-Emergent Adverse Events [Up to 2 years]
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 to Disease Progression (Groups 2 and 3 Only) [From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years)]
This is a measure of the time from the start of the study to the time of documented disease progression.
- Overall Survival (Groups 2 and 3 Only) [From start of treatment until death or data analysis cut off (Up to 3.4 years)]
This is a measure of the time of survival from first dose to documentation of death
- Duration of Response (Groups 2 and 3 Only) [From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)]
This is a measure of the amount of time in which the tumor responded to therapy.
Eligibility Criteria
Criteria
Ages Eligible for Study:
4 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00617890
Other Study ID Numbers:
- P04720
First Posted:
Feb 18, 2008
Last Update Posted:
Aug 23, 2018
Last Verified:
Jul 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Merck Sharp & Dohme LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 35 | 33 | 35 | 116 |
| Received Treatment | 34 | 33 | 34 | 115 |
| COMPLETED | 4 | 5 | 0 | 1 |
| NOT COMPLETED | 31 | 28 | 35 | 115 |
Baseline Characteristics
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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 of all reporting groups |
| Overall Participants | 35 | 33 | 35 | 116 | 219 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
23.7
(15.5)
|
20.1
(10.3)
|
27.5
(15.3)
|
24.6
(11.4)
|
24.3
(12.8)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
14
40%
|
13
39.4%
|
11
31.4%
|
43
37.1%
|
81
37%
|
| Male |
21
60%
|
20
60.6%
|
24
68.6%
|
73
62.9%
|
138
63%
|
Outcome Measures
| Title | Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in Group 3 with evaluable data. |
| Arm/Group Title | Group 3: 10 mg/kg |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 84 |
| Number [Participants] |
6
17.1%
|
| Title | Number of Participants With >= 25% Change in Tumor Proliferation After Exposure to Robatumumab (Group 1 Only) |
|---|---|
| Description | Tumor proliferation was measured using Ki-67 levels. Ki-67 is nuclear protein associated with cellular proliferation. |
| Time Frame | Approximately 14 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group 1 Participants; this outcome was not evaluated due to early termination of the study. |
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 0 | 0 |
| Title | Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group 2 participants with evaluable data. |
| Arm/Group Title | Group 2: 10 mg/kg |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 29 |
| Number [Participants] |
6
17.1%
|
| Title | Overall Survival |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All study participants |
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 35 | 33 | 35 | 116 |
| Number [Participants] |
17
48.6%
|
16
48.5%
|
7
20%
|
28
24.1%
|
| Title | Time Until Tumor Relapse (Group 1 Only) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group 1 participants; this outcome was not evaluated due to early termination of the study. |
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 0 | 0 |
| Title | Area Under the Concentration-time Curve (AUC) of Serum Levels of Robatumumab (Group 1 Only) |
|---|---|
| Description | |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group 1, both dose levels: this outcome was not evaluated due to early termination of the study. |
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 0 | 0 |
| Title | Incidence of Anti-robatumumab Antibodies |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was not evaluated due to early termination of the study. |
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Number of Participants Experiencing Treatment-Emergent Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants receiving study drug. |
| Arm/Group Title | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 34 | 33 | 34 | 115 |
| Number [Participants] |
31
88.6%
|
30
90.9%
|
31
88.6%
|
112
96.6%
|
| Title | Time to Disease Progression (Groups 2 and 3 Only) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Groups 2 and 3; this outcome was not evaluated due to early termination of the study |
| Arm/Group Title | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 0 | 0 |
| Title | Overall Survival (Groups 2 and 3 Only) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group 2 and 3 Participants |
| Arm/Group Title | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 35 | 116 |
| Median (95% Confidence Interval) [Months] |
8.18
|
6.93
|
| Title | Duration of Response (Groups 2 and 3 Only) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Group 2 and 3 participants; this outcome was not evaluated due to early termination of the study |
| Arm/Group Title | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | Adverse events are reported from enrollment up to 5 weeks after the end of treatment (up to 2 years) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All treated participants; 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. | |||||||
| Arm/Group Title | Group 1: 0.3mg/kg | Group 1: 10mg/kg | Group 2: 10mg/kg | Group 3: 10mg/kg | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| Group 1: 0.3mg/kg | Group 1: 10mg/kg | Group 2: 10mg/kg | Group 3: 10mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Group 1: 0.3mg/kg | Group 1: 10mg/kg | Group 2: 10mg/kg | Group 3: 10mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/34 (50%) | 8/33 (24.2%) | 12/34 (35.3%) | 57/115 (49.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 3/115 (2.6%) | 3 |
| FEBRILE BONE MARROW APLASIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| FEBRILE NEUTROPENIA | 2/34 (5.9%) | 2 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| THROMBOCYTOPENIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 2 | 4/115 (3.5%) | 6 |
| Cardiac disorders | ||||||||
| ATRIAL FIBRILLATION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| CARDIAC FAILURE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| CARDIO-RESPIRATORY ARREST | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| TACHYCARDIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Congenital, familial and genetic disorders | ||||||||
| APLASIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 2 |
| Eye disorders | ||||||||
| BLINDNESS UNILATERAL | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 1/115 (0.9%) | 1 |
| VISION BLURRED | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Gastrointestinal disorders | ||||||||
| ABDOMINAL PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 3/115 (2.6%) | 3 |
| CONSTIPATION | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| DIARRHOEA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| GASTROINTESTINAL PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| ILEUS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| NAUSEA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| RETROPERITONEAL HAEMORRHAGE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| UPPER GASTROINTESTINAL HAEMORRHAGE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| VOMITING | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| General disorders | ||||||||
| ASTHENIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| CHEST PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 4/115 (3.5%) | 4 |
| CONDITION AGGRAVATED | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| DEVICE DISLOCATION | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| DRUG WITHDRAWAL SYNDROME | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| FATIGUE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| GENERAL PHYSICAL HEALTH DETERIORATION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| HYPERTHERMIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| INFLUENZA LIKE ILLNESS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| MALAISE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| MUCOSAL INFLAMMATION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| MULTI-ORGAN FAILURE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| OEDEMA PERIPHERAL | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| PAIN | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 11/115 (9.6%) | 13 |
| PERFORMANCE STATUS DECREASED | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| PYREXIA | 1/34 (2.9%) | 1 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 7/115 (6.1%) | 11 |
| Hepatobiliary disorders | ||||||||
| HEPATIC HAEMORRHAGE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| JAUNDICE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Infections and infestations | ||||||||
| APPENDICITIS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| BRONCHOPNEUMONIA | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| CENTRAL NERVOUS SYSTEM INFECTION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| GASTROENTERITIS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| GASTROENTERITIS VIRAL | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| HERPES ZOSTER | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| INFECTION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| OTITIS MEDIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| PNEUMONIA | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| PNEUMONIA VIRAL | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| POST PROCEDURAL INFECTION | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| POSTOPERATIVE WOUND INFECTION | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| SEPSIS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| URINARY TRACT INFECTION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 2 |
| Injury, poisoning and procedural complications | ||||||||
| BRAIN HERNIATION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| HUMERUS FRACTURE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| POSTOPERATIVE RESPIRATORY DISTRESS | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| PROCEDURAL HYPOTENSION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| RIB FRACTURE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 2 |
| TOXICITY TO VARIOUS AGENTS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| WOUND NECROSIS | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| Investigations | ||||||||
| BIOPSY BONE ABNORMAL | 0/34 (0%) | 0 | 1/33 (3%) | 2 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| BLOOD POTASSIUM DECREASED | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| DECREASED APPETITE | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| HYPERGLYCAEMIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| ARTHRALGIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| BACK PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 3/115 (2.6%) | 4 |
| BURSITIS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| FLANK PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| HYPERCREATINAEMIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| MUSCULOSKELETAL PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| CANCER PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| MALIGNANT PLEURAL EFFUSION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| METASTASES TO LUNG | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| OSTEOSARCOMA RECURRENT | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| TUMOUR PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 3/115 (2.6%) | 3 |
| Nervous system disorders | ||||||||
| ALTERED STATE OF CONSCIOUSNESS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| COMA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 1/115 (0.9%) | 1 |
| CONVULSION | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| ENCEPHALOPATHY | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| HEADACHE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| HEPATIC ENCEPHALOPATHY | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| MENINGEAL DISORDER | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| MYOCLONUS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| NERVE COMPRESSION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| PERIPHERAL SENSORY NEUROPATHY | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 2 |
| SPINAL CORD COMPRESSION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| SYNCOPE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| TOXIC ENCEPHALOPATHY | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Psychiatric disorders | ||||||||
| AGITATION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| ANXIETY | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| CONFUSIONAL STATE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| INSOMNIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| MENTAL STATUS CHANGES | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Renal and urinary disorders | ||||||||
| NEPHROLITHIASIS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| ACUTE RESPIRATORY DISTRESS SYNDROME | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| ACUTE RESPIRATORY FAILURE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| BRONCHIAL DISORDER | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| DYSPNOEA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 2/34 (5.9%) | 2 | 3/115 (2.6%) | 3 |
| DYSPNOEA AT REST | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| DYSPNOEA EXERTIONAL | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| EPISTAXIS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| HAEMOTHORAX | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| HYPOXIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| PLEURAL EFFUSION | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| PNEUMOTHORAX | 4/34 (11.8%) | 4 | 1/33 (3%) | 2 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| PULMONARY EMBOLISM | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| PULMONARY TOXICITY | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| RESPIRATORY DISTRESS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 6/115 (5.2%) | 7 |
| RESPIRATORY FAILURE | 3/34 (8.8%) | 3 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 5/115 (4.3%) | 5 |
| Skin and subcutaneous tissue disorders | ||||||||
| PETECHIAE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Surgical and medical procedures | ||||||||
| LEG AMPUTATION | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| MEDICAL DEVICE REMOVAL | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| THORACOTOMY | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| WOUND TREATMENT | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| Vascular disorders | ||||||||
| HAEMORRHAGE | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| HYPOTENSION | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| SHOCK HAEMORRHAGIC | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Group 1: 0.3mg/kg | Group 1: 10mg/kg | Group 2: 10mg/kg | Group 3: 10mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/34 (82.4%) | 30/33 (90.9%) | 29/34 (85.3%) | 104/115 (90.4%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 6/34 (17.6%) | 8 | 2/33 (6.1%) | 3 | 3/34 (8.8%) | 4 | 22/115 (19.1%) | 44 |
| LEUKOPENIA | 1/34 (2.9%) | 1 | 2/33 (6.1%) | 2 | 0/34 (0%) | 0 | 3/115 (2.6%) | 4 |
| NEUTROPENIA | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 6/115 (5.2%) | 6 |
| THROMBOCYTOPENIA | 1/34 (2.9%) | 2 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 17/115 (14.8%) | 35 |
| Cardiac disorders | ||||||||
| SINUS TACHYCARDIA | 2/34 (5.9%) | 2 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| TACHYCARDIA | 2/34 (5.9%) | 2 | 1/33 (3%) | 1 | 1/34 (2.9%) | 1 | 4/115 (3.5%) | 4 |
| Ear and labyrinth disorders | ||||||||
| TINNITUS | 2/34 (5.9%) | 2 | 3/33 (9.1%) | 3 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Gastrointestinal disorders | ||||||||
| ABDOMINAL PAIN | 1/34 (2.9%) | 1 | 3/33 (9.1%) | 3 | 0/34 (0%) | 0 | 9/115 (7.8%) | 13 |
| ABDOMINAL PAIN UPPER | 2/34 (5.9%) | 2 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 9/115 (7.8%) | 10 |
| CONSTIPATION | 9/34 (26.5%) | 9 | 9/33 (27.3%) | 10 | 3/34 (8.8%) | 3 | 34/115 (29.6%) | 43 |
| DIARRHOEA | 3/34 (8.8%) | 6 | 6/33 (18.2%) | 11 | 2/34 (5.9%) | 2 | 29/115 (25.2%) | 42 |
| DYSPEPSIA | 1/34 (2.9%) | 1 | 1/33 (3%) | 2 | 2/34 (5.9%) | 2 | 4/115 (3.5%) | 5 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 6/115 (5.2%) | 6 |
| NAUSEA | 13/34 (38.2%) | 20 | 12/33 (36.4%) | 18 | 5/34 (14.7%) | 6 | 35/115 (30.4%) | 48 |
| STOMATITIS | 2/34 (5.9%) | 2 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 6/115 (5.2%) | 6 |
| VOMITING | 9/34 (26.5%) | 12 | 8/33 (24.2%) | 9 | 3/34 (8.8%) | 4 | 25/115 (21.7%) | 40 |
| General disorders | ||||||||
| ASTHENIA | 0/34 (0%) | 0 | 1/33 (3%) | 4 | 1/34 (2.9%) | 1 | 13/115 (11.3%) | 18 |
| CHEST PAIN | 7/34 (20.6%) | 8 | 3/33 (9.1%) | 3 | 3/34 (8.8%) | 3 | 10/115 (8.7%) | 12 |
| FATIGUE | 7/34 (20.6%) | 10 | 7/33 (21.2%) | 8 | 7/34 (20.6%) | 7 | 23/115 (20%) | 28 |
| MUCOSAL INFLAMMATION | 0/34 (0%) | 0 | 2/33 (6.1%) | 7 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| OEDEMA PERIPHERAL | 2/34 (5.9%) | 2 | 2/33 (6.1%) | 2 | 3/34 (8.8%) | 3 | 4/115 (3.5%) | 4 |
| PAIN | 4/34 (11.8%) | 4 | 4/33 (12.1%) | 4 | 2/34 (5.9%) | 2 | 9/115 (7.8%) | 11 |
| PYREXIA | 9/34 (26.5%) | 11 | 11/33 (33.3%) | 13 | 6/34 (17.6%) | 7 | 21/115 (18.3%) | 37 |
| Infections and infestations | ||||||||
| BRONCHITIS | 2/34 (5.9%) | 2 | 1/33 (3%) | 1 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| NASOPHARYNGITIS | 1/34 (2.9%) | 1 | 2/33 (6.1%) | 2 | 2/34 (5.9%) | 2 | 1/115 (0.9%) | 2 |
| RHINITIS | 2/34 (5.9%) | 2 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| SINUSITIS | 2/34 (5.9%) | 2 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 5/115 (4.3%) | 6 |
| UPPER RESPIRATORY TRACT INFECTION | 7/34 (20.6%) | 7 | 3/33 (9.1%) | 4 | 1/34 (2.9%) | 1 | 7/115 (6.1%) | 13 |
| URINARY TRACT INFECTION | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 4/34 (11.8%) | 4 | 8/115 (7%) | 12 |
| Injury, poisoning and procedural complications | ||||||||
| INCISION SITE PAIN | 1/34 (2.9%) | 1 | 2/33 (6.1%) | 2 | 1/34 (2.9%) | 1 | 2/115 (1.7%) | 3 |
| POST PROCEDURAL HAEMORRHAGE | 2/34 (5.9%) | 2 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 0/115 (0%) | 0 |
| POST-THORACOTOMY PAIN SYNDROME | 3/34 (8.8%) | 3 | 1/33 (3%) | 1 | 1/34 (2.9%) | 1 | 0/115 (0%) | 0 |
| PROCEDURAL PAIN | 13/34 (38.2%) | 16 | 6/33 (18.2%) | 7 | 1/34 (2.9%) | 1 | 2/115 (1.7%) | 2 |
| Investigations | ||||||||
| ASPARTATE AMINOTRANSFERASE INCREASED | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 8/115 (7%) | 11 |
| BLOOD ALKALINE PHOSPHATASE INCREASED | 1/34 (2.9%) | 1 | 2/33 (6.1%) | 2 | 1/34 (2.9%) | 1 | 3/115 (2.6%) | 3 |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 9/115 (7.8%) | 11 |
| HAEMOGLOBIN DECREASED | 5/34 (14.7%) | 6 | 6/33 (18.2%) | 12 | 1/34 (2.9%) | 1 | 3/115 (2.6%) | 4 |
| PLATELET COUNT DECREASED | 3/34 (8.8%) | 4 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 2/115 (1.7%) | 6 |
| WEIGHT DECREASED | 1/34 (2.9%) | 1 | 1/33 (3%) | 1 | 2/34 (5.9%) | 2 | 11/115 (9.6%) | 13 |
| Metabolism and nutrition disorders | ||||||||
| DECREASED APPETITE | 5/34 (14.7%) | 6 | 4/33 (12.1%) | 5 | 4/34 (11.8%) | 4 | 27/115 (23.5%) | 37 |
| DEHYDRATION | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 1/34 (2.9%) | 1 | 6/115 (5.2%) | 6 |
| HYPERGLYCAEMIA | 6/34 (17.6%) | 11 | 3/33 (9.1%) | 6 | 1/34 (2.9%) | 1 | 12/115 (10.4%) | 18 |
| HYPOALBUMINAEMIA | 2/34 (5.9%) | 2 | 3/33 (9.1%) | 3 | 0/34 (0%) | 0 | 5/115 (4.3%) | 5 |
| HYPOCALCAEMIA | 3/34 (8.8%) | 6 | 0/33 (0%) | 0 | 2/34 (5.9%) | 2 | 4/115 (3.5%) | 8 |
| HYPOKALAEMIA | 3/34 (8.8%) | 4 | 2/33 (6.1%) | 3 | 0/34 (0%) | 0 | 6/115 (5.2%) | 8 |
| HYPONATRAEMIA | 4/34 (11.8%) | 5 | 2/33 (6.1%) | 2 | 1/34 (2.9%) | 1 | 2/115 (1.7%) | 2 |
| HYPOPHOSPHATAEMIA | 1/34 (2.9%) | 1 | 2/33 (6.1%) | 2 | 1/34 (2.9%) | 1 | 2/115 (1.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||
| ARTHRALGIA | 4/34 (11.8%) | 4 | 2/33 (6.1%) | 4 | 3/34 (8.8%) | 3 | 10/115 (8.7%) | 12 |
| BACK PAIN | 5/34 (14.7%) | 5 | 4/33 (12.1%) | 4 | 6/34 (17.6%) | 7 | 15/115 (13%) | 19 |
| BONE PAIN | 0/34 (0%) | 0 | 1/33 (3%) | 1 | 4/34 (11.8%) | 4 | 6/115 (5.2%) | 6 |
| FLANK PAIN | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 2/34 (5.9%) | 3 | 2/115 (1.7%) | 5 |
| MUSCLE SPASMS | 2/34 (5.9%) | 3 | 3/33 (9.1%) | 6 | 2/34 (5.9%) | 2 | 11/115 (9.6%) | 13 |
| MUSCULAR WEAKNESS | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 2/34 (5.9%) | 2 | 3/115 (2.6%) | 3 |
| MUSCULOSKELETAL CHEST PAIN | 0/34 (0%) | 0 | 2/33 (6.1%) | 2 | 4/34 (11.8%) | 4 | 7/115 (6.1%) | 8 |
| MUSCULOSKELETAL PAIN | 3/34 (8.8%) | 3 | 2/33 (6.1%) | 2 | 1/34 (2.9%) | 1 | 13/115 (11.3%) | 16 |
| MYALGIA | 1/34 (2.9%) | 1 | 0/33 (0%) | 0 | 2/34 (5.9%) | 2 | 6/115 (5.2%) | 7 |
| NECK PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 2/34 (5.9%) | 2 | 6/115 (5.2%) | 6 |
| PAIN IN EXTREMITY | 7/34 (20.6%) | 9 | 4/33 (12.1%) | 8 | 6/34 (17.6%) | 8 | 12/115 (10.4%) | 25 |
| PAIN IN JAW | 2/34 (5.9%) | 2 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 2/115 (1.7%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| TUMOUR PAIN | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 2/34 (5.9%) | 2 | 8/115 (7%) | 11 |
| Nervous system disorders | ||||||||
| DIZZINESS | 1/34 (2.9%) | 1 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 7/115 (6.1%) | 10 |
| HEADACHE | 9/34 (26.5%) | 16 | 7/33 (21.2%) | 8 | 7/34 (20.6%) | 10 | 24/115 (20.9%) | 57 |
| SOMNOLENCE | 1/34 (2.9%) | 1 | 1/33 (3%) | 1 | 0/34 (0%) | 0 | 7/115 (6.1%) | 9 |
| Psychiatric disorders | ||||||||
| ANXIETY | 2/34 (5.9%) | 2 | 3/33 (9.1%) | 3 | 3/34 (8.8%) | 3 | 18/115 (15.7%) | 24 |
| DEPRESSION | 1/34 (2.9%) | 1 | 3/33 (9.1%) | 4 | 2/34 (5.9%) | 2 | 4/115 (3.5%) | 4 |
| INSOMNIA | 4/34 (11.8%) | 4 | 3/33 (9.1%) | 4 | 2/34 (5.9%) | 2 | 20/115 (17.4%) | 20 |
| Renal and urinary disorders | ||||||||
| DYSURIA | 0/34 (0%) | 0 | 0/33 (0%) | 0 | 3/34 (8.8%) | 3 | 2/115 (1.7%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| COUGH | 10/34 (29.4%) | 10 | 7/33 (21.2%) | 9 | 6/34 (17.6%) | 6 | 16/115 (13.9%) | 19 |
| DYSPNOEA | 6/34 (17.6%) | 7 | 4/33 (12.1%) | 4 | 4/34 (11.8%) | 4 | 7/115 (6.1%) | 7 |
| DYSPNOEA EXERTIONAL | 4/34 (11.8%) | 5 | 2/33 (6.1%) | 2 | 2/34 (5.9%) | 2 | 11/115 (9.6%) | 11 |
| EPISTAXIS | 3/34 (8.8%) | 6 | 2/33 (6.1%) | 5 | 0/34 (0%) | 0 | 9/115 (7.8%) | 11 |
| HAEMOPTYSIS | 3/34 (8.8%) | 3 | 2/33 (6.1%) | 2 | 2/34 (5.9%) | 3 | 2/115 (1.7%) | 3 |
| OROPHARYNGEAL PAIN | 3/34 (8.8%) | 4 | 1/33 (3%) | 1 | 2/34 (5.9%) | 2 | 11/115 (9.6%) | 15 |
| PLEURAL EFFUSION | 3/34 (8.8%) | 4 | 1/33 (3%) | 1 | 1/34 (2.9%) | 2 | 6/115 (5.2%) | 6 |
| PNEUMOTHORAX | 4/34 (11.8%) | 5 | 2/33 (6.1%) | 3 | 1/34 (2.9%) | 1 | 2/115 (1.7%) | 2 |
| RHINORRHOEA | 1/34 (2.9%) | 1 | 5/33 (15.2%) | 10 | 1/34 (2.9%) | 1 | 1/115 (0.9%) | 1 |
| WHEEZING | 3/34 (8.8%) | 4 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 3/115 (2.6%) | 4 |
| Skin and subcutaneous tissue disorders | ||||||||
| ALOPECIA | 1/34 (2.9%) | 1 | 2/33 (6.1%) | 2 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| PRURITUS | 6/34 (17.6%) | 8 | 4/33 (12.1%) | 6 | 2/34 (5.9%) | 2 | 5/115 (4.3%) | 6 |
| RASH | 3/34 (8.8%) | 6 | 2/33 (6.1%) | 2 | 1/34 (2.9%) | 1 | 11/115 (9.6%) | 12 |
| SUBCUTANEOUS EMPHYSEMA | 2/34 (5.9%) | 2 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| URTICARIA | 3/34 (8.8%) | 4 | 0/33 (0%) | 0 | 0/34 (0%) | 0 | 1/115 (0.9%) | 1 |
| Vascular disorders | ||||||||
| HYPOTENSION | 2/34 (5.9%) | 2 | 1/33 (3%) | 1 | 2/34 (5.9%) | 2 | 6/115 (5.2%) | 6 |
Limitations/Caveats
The study was stopped prematurely for administrative reasons; not all planned endpoints were analyzed.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of the Sponsor. The Investigator further agrees to provide to the Sponsor 45 days prior to submission any publication, presentation, abstracts, manuscripts, or electronic media that report any results of the study. The Sponsor shall have the right to review and comment.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00617890
Other Study ID Numbers:
- P04720
First Posted:
Feb 18, 2008
Last Update Posted:
Aug 23, 2018
Last Verified:
Jul 1, 2018