Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone
Primary Purpose
GCT, Giant Cell Tumor of Bone
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Denosumab
Calcium/Vitamin D
Sponsored by
About this trial
This is an interventional treatment trial for GCT focused on measuring Giant Cell Tumor of Bone
Eligibility Criteria
Inclusion Criteria:
- Adults, 18 years and older
- Histologically confirmed and measurable giant cell tumor (GCT)
- Recurrent GCT confirmed by radiology or unresectable GCT
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion Criteria:
- Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab
- Radiation to affected region within 28 days before enrollment to study
- Known diagnosis of osteosarcoma or brown tumor of bone
- Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ
- Concurrent treatment with bisphosphonates, calcitonin, or interferon.
Other criteria also apply.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Denosumab
Arm Description
Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
Outcomes
Primary Outcome Measures
Percentage of Participants With Giant Cell Tumor Response
A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent < 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.
Secondary Outcome Measures
Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine
Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time.
Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)
Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time.
Serum Denosumab Trough Concentrations
Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).
Number of Participants With Adverse Events (AEs)
An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug.
Number of Participants With Anti-Denosumab Antibodies
Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00396279
Brief Title
Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone
Official Title
An Open-Label, Multi-Center, Phase 2 Safety and Efficacy Study of Denosumab (AMG 162) in Subjects With Recurrent or Unresectable Giant Cell Tumor (GCT) of Bone
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
July 10, 2006 (Actual)
Primary Completion Date
April 7, 2008 (Actual)
Study Completion Date
February 1, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GCT, Giant Cell Tumor of Bone
Keywords
Giant Cell Tumor of Bone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Denosumab
Arm Type
Experimental
Arm Description
Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg doses on Days 8 and 15 of the first month of treatment. All participants were instructed to take daily supplements of at least 500 mg of calcium and 400 IU of vitamin D. Participants were to continue to receive denosumab until one of the following occurred: complete tumor resection, disease progression without clinical benefit, or decision by the participant to discontinue for any reason.
Intervention Type
Biological
Intervention Name(s)
Denosumab
Other Intervention Name(s)
Xgeva®
Intervention Description
Administered by subcutaneous injection
Intervention Type
Dietary Supplement
Intervention Name(s)
Calcium/Vitamin D
Primary Outcome Measure Information:
Title
Percentage of Participants With Giant Cell Tumor Response
Description
A treatment response was defined for participants with tissue samples obtained and measured by histopathology as: • at least 90% elimination of giant cells relative to Baseline, or • complete elimination of giant cells in cases where giant cells represent < 5% of tumor cells. A response was defined for participants who have only radiographs (histopathology not available) as lack of progression of the target lesion at week 25 by radiographic measurements compared with Baseline. For participants with both a core biopsy and resected tissue obtained, the sample closest to week 25 was used in the analysis.
Time Frame
From enrollment until 25 weeks
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Urinary N-telopeptide Corrected for Urine Creatinine
Description
Urinary N-telopeptide (of type 1 collagen) corrected for urine creatinine (uNTX/Cr) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in uNTX/Cr was measured over time.
Time Frame
Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
Title
Percent Change From Baseline in Serum C-terminus Peptide (of Type 1 Collagen)
Description
Serum C-terminus peptide (of type 1 collagen; CTX1) is a bone turnover marker used to measure the activity of denosumab. Percent change from Baseline in CTX was measured over time.
Time Frame
Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81
Title
Serum Denosumab Trough Concentrations
Description
Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA).
Time Frame
Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49.
Title
Number of Participants With Adverse Events (AEs)
Description
An adverse event is defined as an undesirable medical occurrence (e.g., sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the participant at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) based on the following general guideline: Grade 1: Mild AE Grade 2: Moderate AE Grade 3: Severe AE Grade 4: Life-threatening or disabling AE Grade 5: Death related to AE. AEs were assessed by the Investigator for relatedness to study drug.
Time Frame
From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months
Title
Number of Participants With Anti-Denosumab Antibodies
Description
Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study.
Time Frame
From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults, 18 years and older
Histologically confirmed and measurable giant cell tumor (GCT)
Recurrent GCT confirmed by radiology or unresectable GCT
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion Criteria:
Pateints for whom surgery to the affected limb/area is planned within 27 days after receiving 1st dose of denosumab
Radiation to affected region within 28 days before enrollment to study
Known diagnosis of osteosarcoma or brown tumor of bone
Known history of second malignancy within the past 5 years, except for basal cell carcinoma or cervical carcinoma in situ
Concurrent treatment with bisphosphonates, calcitonin, or interferon.
Other criteria also apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
22711702
Citation
Branstetter DG, Nelson SD, Manivel JC, Blay JY, Chawla S, Thomas DM, Jun S, Jacobs I. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24. doi: 10.1158/1078-0432.CCR-12-0578. Epub 2012 Jun 18.
Results Reference
background
PubMed Identifier
20149736
Citation
Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, Dansey R, Jun S. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80. doi: 10.1016/S1470-2045(10)70010-3. Epub 2010 Feb 10.
Results Reference
background
PubMed Identifier
30231890
Citation
Engellau J, Seeger L, Grimer R, Henshaw R, Gelderblom H, Choy E, Chawla S, Reichardt P, O'Neal M, Feng A, Jacobs I, Roberts ZJ, Braun A, Bach BA. Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone. World J Surg Oncol. 2018 Sep 19;16(1):191. doi: 10.1186/s12957-018-1478-3.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone
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