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To determine how safe and effective denosumab is in treating patients with giant cell tumor of bone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Denosumab | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Denosumab | Biological | Administered by subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From enrollment until 25 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 |
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Inclusion Criteria:
Exclusion Criteria:
Other criteria also apply.
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22711702 | Background | 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. | |
| 20149736 | Background | 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. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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First patient enrolled 10 July 2006; Last patient enrolled 25 January 2008. Results data are reported as of the data cut-off date of 07 April 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Denosumab | Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Denosumab | Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The efficacy analysis set included participants with a Baseline histology assessment and at least 1 postdose histology assessment from weeks 5-25; or a Baseline radiology assessment and at least 1 postdose radiology assessment from weeks 5-25. Evaluable participants had to be on study for at least 28 days after administration of the first dose. | Posted | Number | 95% Confidence Interval | percentage of participants | From enrollment until 25 weeks |
|
up to 1 year 6 months
The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Denosumab 120 mg Q4W | Participants received a dose loading regimen of 3 subcutaneous injections of denosumab 120 mg every week for 3 weeks (study Days 1, 8, and 15), followed by a week of rest, and then 120 mg denosumab once every 4 weeks (Q4W) from Day 29. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 |
| ID | Term |
|---|---|
| D018212 | Giant Cell Tumor of Bone |
| ID | Term |
|---|---|
| D005870 | Giant Cell Tumors |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D000069448 | Denosumab |
| D002118 | Calcium |
| D014807 | Vitamin D |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Calcium/Vitamin D | Dietary Supplement |
|
| 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. | Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 |
| Serum Denosumab Trough Concentrations | Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA). | Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49. |
| 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. | From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months |
| Number of Participants With Anti-Denosumab Antibodies | Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study. | From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months. |
| 30231890 | Derived | 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. |
| Physician Decision |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Giant Cell Tumor Disease Type | Number | participants |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status | 0: Fully active, able to carry on all pre-disease performance without restriction;
| Number | participants |
|
| Percent of giant cells in tumor on pre-treatment biopsy | Mean | Standard Deviation | percentage of giant cells in tumor |
|
| Location of target lesion | Number | participants |
|
| OG000 | Denosumab | Participants received denosumab 120 mg once every 4 weeks (Q4W), with an additional 120 mg dose 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. |
|
|
| Secondary | 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. | Efficacy Analysis Set with available data at each time point (n). | Posted | Median | Inter-Quartile Range | percent change | Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 |
|
|
|
| Secondary | 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. | Efficacy Analysis Set with available data at each time point (n). | Posted | Median | Inter-Quartile Range | percent change | Baseline and Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 |
|
|
|
| Secondary | Serum Denosumab Trough Concentrations | Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA). | The pharmacokinetics analysis set included participants who received at least 1 dose of denosumab and for whom at least 1 serum denosumab trough concentration was available. 'n' indicates the number of participants with available data at each time point. | Posted | Mean | Standard Deviation | ng/mL | Blood samples were collected on Days 1 (baseline), 8, 15 and Weeks 5 (Day 29), 9, 13, 25, and 49. |
|
|
|
| Secondary | 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. | All participants who received at least 1 dose of denosumab. | Posted | Number | participants | From the first dose of study drug until the data cut-off date of April 7 2008; a maximum of 18 months |
|
|
|
| Secondary | Number of Participants With Anti-Denosumab Antibodies | Validated immunoassays were used to test for the presence of anti-denosumab antibodies throughout the study. | Participants who received at least 1 dose of denosumab and had at least 1 anti-denosumab antibody sample. | Posted | Number | participants | From enrollment until the data cut-off date of April 7 2008; a maximum time of 18 months. |
|
|
|
| 5 |
| 37 |
| 25 |
| 37 |
| Lower respiratory tract infection | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 11.0 | Systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 11.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 11.0 | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA 11.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 11.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 11.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| D009369 | Neoplasms |
| D018213 | Neoplasms, Bone Tissue |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D008673 | Metals, Alkaline Earth |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D008670 | Metals |
| D001779 | Blood Coagulation Factors |
| D001685 | Biological Factors |
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| Title | Measurements |
|---|---|
|
| Week 17 (n=26) |
|
| Week 21 (n=24) |
|
| Week 25 (n=20) |
|
| Week 29 (n=21) |
|
| Week 33 (n=15) |
|
| Week 37 (n=13) |
|
| Week 41 (n=11) |
|
| Week 45 (n=8) |
|
| Week 49 (n=7) |
|
| Week 53 (N=8) |
|
| Week 57 (n=6) |
|
| Week 61 (n=3) |
|
| Week 65 (n=3) |
|
| Week 69 (n=4) |
|
| Week 73 (n=1) |
|
| Week 77 (n=2) |
|
| Week 81 (n=2) |
|
| Title | Measurements |
|---|---|
|
| Week 17 (n=28) |
|
| Week 21 (n=26) |
|
| Week 25 (n=24) |
|
| Week 29 (n=21) |
|
| Week 33 (n=16) |
|
| Week 37 (n=14) |
|
| Week 41 (n=10) |
|
| Week 45 (n=8) |
|
| Week 49 (n=7) |
|
| Week 53 (N=8) |
|
| Week 57 (n=6) |
|
| Week 61 (n=4) |
|
| Week 65 (n=3) |
|
| Week 69 (n=4) |
|
| Week 73 (n=2) |
|
| Week 77 (n=2) |
|
| Week 81 (n=2) |
|
|
| Day 29 (n=33) |
|
| Week 9 (n=32) |
|
| Week 13 (n=25) |
|
| Week 25 (n=23) |
|
| Week 49 (n=9) |
|
| Title | Measurements |
|---|
|
| AE leading to study discontinuation |
|
| AE leading to study drug discontinuation |
|
| CTCAE Grade 3, 4, or 5 |
|
| Any AE related to study drug |
|