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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-001662-42 | EudraCT Number |
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This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.
This is a global randomized double-blind placebo-controlled study in patients with Stage IV untreated non-small cell lung cancer (NSCLC) with or without bone metastasis. Eligible participants are to receive 4 to 6 cycles of a standard of care platinum-doublet chemotherapy regimen. Participants will be randomized in a 2:1 ratio to receive denosumab or matching placebo with the first investigational product dose coinciding with participant's first cycle of chemotherapy and continuing until the primary analysis, unacceptable toxicity, withdrawal of consent, death, or lost to follow-up. Participants who discontinued the investigational product early (ie, before primary analysis) were followed for disease status and survival. The primary analysis took place when 149 events of death had been reported. All participants were followed for 2 years after the last dose of blinded investigational product.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W. |
|
| Denosumab | Experimental | Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Denosumab | Drug | Administered by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8; could be administered as often as every 3 weeks (Q3W) to participants receiving Q3W chemotherapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | Overall survival was calculated as the time from the date of randomization to the date of death from any cause. Participants last known to be alive were censored at the last contact date. | From randomization until the end of study; median time on study was 9.64 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of Tumor Tissue RANK Expression With Overall Survival | To assess whether the treatment effect on overall survival was correlated with receptor activator of nuclear factor (NF)-κB (RANK) protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANK expression level and OS was evaluated using a Cox proportional hazard models that included RANK expression level stratified by the randomization stratification factors in the corresponding treatment group. |
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Inclusion Criteria:
Histologically or cytologically confirmed stage IV non-small cell lung carcinoma (NSCLC), according to 7th Tumor/Node/Metastasis (TNM) classification (cytological specimens obtained by bronchial washing or brushing, or fine-needle aspiration are acceptable)
Subject has available and has provided consent to release to the sponsor (or designee) a tumor block with confirmed tumor content (or approximately 20 unstained charged slides [a minimum of 7 slides is mandatory]) and the corresponding pathology report
Planned to receive 4 to 6 cycles of pemetrexed or gemcitabine in combination with cisplatin or carboplatin
• For subjects to receive pemetrexed, planned to receive vitamin B12 and folate per pemetrexed approved labeling
Radiographically evaluable (measurable or non-measurable) disease (according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
Other inclusion criteria may apply
Exclusion Criteria:
Known presence of documented sensitizing epidermal growth factor receptor (EGFR) activating mutation or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation (screening following local standards, but strongly encouraged in non-squamous histology)
Known brain metastases (systematic screening of patients not mandatory)
Any prior systemic therapy (before randomization) for the treatment of NSCLC (including chemoradiation), except if for non-metastatic disease and was completed at least 6 months prior to randomization
Planned to receive bevacizumab
Significant dental/oral disease, including prior history or current evidence of osteonecrosis/ osteomyelitis of the jaw, or with the following:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Goodyear | Arizona | 85338 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34543941 | Background | Peters S, Danson S, Ejedepang D, Dafni U, Hasan B, Radcliffe HS, Bustin F, Crequit J, Coate L, Guillot M, Surmont V, Rauch D, Rudzki J, O'Mahony D, Barneto Aranda I, Scherz A, Tsourti Z, Roschitzki-Voser H, Pochesci A, Demonty G, Stahel RA, O'Brien M. Combined, patient-level, analysis of two randomised trials evaluating the addition of denosumab to standard first-line chemotherapy in advanced NSCLC - The ETOP/EORTC SPLENDOUR and AMGEN-249 trials. Lung Cancer. 2021 Nov;161:76-85. doi: 10.1016/j.lungcan.2021.09.002. Epub 2021 Sep 9. |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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Participants were randomized in a 2:1 ratio to receive denosumab or placebo. Randomization was stratified based on the presence of bone metastasis (yes or no), histology (squamous versus non-squamous), and geographic region (North America, Western Europe/Australia, and rest of world [ROW]).
This study was conducted at 57 centers in 10 countries including the United Kingdom, Netherlands, France, Italy, Germany, Czech Republic, United States, Canada, Australia and Greece. Participants were enrolled from 31 December 2013 to 21 May 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Zoledronic acid | Drug | Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy. |
|
|
| Placebo to Denosumab | Drug | Administered by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8; could be administered as often as every 3 weeks (Q3W) to participants receiving Q3W chemotherapy. |
|
| Standard Chemotherapy | Drug | Standard of care chemotherapy consisting of pemetrexed or gemcitabine in combination with cisplatin or carboplatin administered according to local practice. |
|
| Placebo to Zoledronic Acid | Drug | Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy. |
|
| From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
| Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival | To assess whether the treatment effect on overall survival was correlated with RANK ligand (RANKL) protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANKL expression level and OS was evaluated using a Cox proportional hazard models that included RANKL expression level stratified by the randomization stratification factors in the corresponding treatment group. | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
| Objective Response Rate | Objective response rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) based on modified RECIST 1.1 achieved over the study duration. CR: Disappearance of all target and non target lesions, normalization of tumor marker levels and no new lesions. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, disappearance of target lesions with persistence of one or more non-target lesions and/or maintenance of tumor marker levels above normal limits and no new lesions. Participants who underwent surgical resection while on study were not evaluated for response after the surgery. Participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non-responders. | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
| Correlation of Tumor Tissue RANK Expression With Objective Response Rate | To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANK protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANK expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANK expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported. | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
| Correlation of Tumor Tissue RANKL Expression With Objective Response Rate | To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANKL protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANKL expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANKL expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported. | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
| Clinical Benefit Rate | Clinical benefit rate was defined as the percentage of participants with an objective response (CR or PR) or stable disease (SD) or better for at least 16 weeks achieved over the study duration. If a participant underwent surgical resection while on study, the participant was not evaluated for response after the surgery. Participants who did not meet the criteria for clinical benefit by the analysis cutoff date were considered as non-responders. | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
| Progression-free Survival (PFS) | Progression-free survival was defined as the time from randomization to the first observed disease progression per modified RECIST 1.1 criteria or death from any cause. Participants last known to be alive who did not experience disease progression were censored at their last imaging assessment date, last contact date if they were in the survival follow up phase, end of the study date, or the primary analysis cut-off date, whichever was first. If a participant underwent surgical resection while on study, the participant was censored at the last evaluable imaging assessment prior to the surgery. | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
| Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing | Serum samples were analyzed for denosumab using enzyme-linked immunosorbent assay (ELISA) following a validated procedure. The lower limit of quantification for the assay was 20 ng/mL. | Prior to dosing at day 8 and weeks 3, 6, 9, 12, 15, 18, 21 and 24. |
| Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing | Serum samples were analyzed for denosumab using enzyme-linked immunosorbent assay (ELISA) following a validated procedure. The lower limit of quantification for the assay was 20 ng/mL. | Prior to dosing at day 8 and weeks 4, 8, 12, 16, 20 and 24 |
| Number of Participants With Treatment-emergent Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following criteria
Fatal adverse events include only deaths reported on the Adverse Event Case Report Form. | From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. |
| Anaheim |
| California |
| 92801 |
| United States |
| Research Site | Long Beach | California | 90813 | United States |
| Research Site | Los Angeles | California | 90024 | United States |
| Research Site | Los Angeles | California | 90048 | United States |
| Research Site | Farmington | Connecticut | 06030-1628 | United States |
| Research Site | Alexandria | Louisiana | 71301 | United States |
| Research Site | Brewer | Maine | 04412 | United States |
| Research Site | Westminster | Maryland | 21157 | United States |
| Research Site | Fairhaven | Massachusetts | 02719 | United States |
| Research Site | Detroit | Michigan | 48202 | United States |
| Research Site | East Setauket | New York | 11733 | United States |
| Research Site | Durham | North Carolina | 27710 | United States |
| Research Site | Hickory | North Carolina | 28602 | United States |
| Research Site | Winston-Salem | North Carolina | 27157 | United States |
| Research Site | Bismarck | North Dakota | 58501 | United States |
| Research Site | Cincinnati | Ohio | 45267 | United States |
| Research Site | Nashville | Tennessee | 37203 | United States |
| Research Site | Kogarah | New South Wales | 2217 | Australia |
| Research Site | Wahroonga | New South Wales | 2076 | Australia |
| Research Site | Adelaide | South Australia | 5000 | Australia |
| Research Site | Footscray | Victoria | 3011 | Australia |
| Research Site | Parkville | Victoria | 3050 | Australia |
| Research Site | Wodonga | Victoria | 3690 | Australia |
| Research Site | Edmonton | Alberta | T6G 1Z2 | Canada |
| Research Site | Saint John | New Brunswick | E2L 4L2 | Canada |
| Research Site | Greater Sudbury | Ontario | P3E 5J1 | Canada |
| Research Site | Kitchener | Ontario | N2G 1G3 | Canada |
| Research Site | Toronto | Ontario | M5G 2M9 | Canada |
| Research Site | Toronto | Ontario | M9N 1N8 | Canada |
| Research Site | Montreal | Quebec | H2W 1S6 | Canada |
| Research Site | Chomutov | 430 12 | Czechia |
| Research Site | Ostrava-Poruba | 708 52 | Czechia |
| Research Site | Pardubice | 532 03 | Czechia |
| Research Site | Prague | 180 81 | Czechia |
| Research Site | Ústí nad Labem | 401 13 | Czechia |
| Research Site | Caen | 14076 | France |
| Research Site | Dijon | 21079 | France |
| Research Site | Nantes | 44202 | France |
| Research Site | Paris | 75020 | France |
| Research Site | Paris | 75475 | France |
| Research Site | Paris | 75674 | France |
| Research Site | Pessac | 33604 | France |
| Research Site | Reims | 51056 | France |
| Research Site | Saint-Quentin | 02321 | France |
| Research Site | Tours | 37044 | France |
| Research Site | Berlin | 14165 | Germany |
| Research Site | Großhansdorf | 22927 | Germany |
| Research Site | Köln-Merheim | 51109 | Germany |
| Research Site | Ulm | 89081 | Germany |
| Research Site | Athens | 11522 | Greece |
| Research Site | Athens | 12462 | Greece |
| Research Site | Heraklion | 71110 | Greece |
| Research Site | Pátrai | 26504 | Greece |
| Research Site | Thessaloniki | 54622 | Greece |
| Research Site | Thessaloniki | 57010 | Greece |
| Research Site | Monza (MB) | 20900 | Italy |
| Research Site | Orbassano (TO) | 10043 | Italy |
| Research Site | Pavia | 27100 | Italy |
| Research Site | Roma | 00128 | Italy |
| Research Site | Saronno VA | 21047 | Italy |
| Research Site | 's-Hertogenbosch | 5223 GZ | Netherlands |
| Research Site | Arnhem | 6815 AD | Netherlands |
| Research Site | Harderwijk | 3844 DG | Netherlands |
| Research Site | Tilburg | 5022 GC | Netherlands |
| Research Site | Zutphen | 7207 AE | Netherlands |
| Research Site | Bristol | BS2 8ED | United Kingdom |
| Research Site | Exeter | EX2 5DW | United Kingdom |
| Research Site | Glasgow | G42 9LF | United Kingdom |
| Research Site | Guildford | GU2 7XX | United Kingdom |
| Research Site | London | SE1 9RT | United Kingdom |
| Research Site | London | W6 8RF | United Kingdom |
| Research Site | Plymouth | PL6 8DH | United Kingdom |
| Research Site | Preston | PR2 9HT | United Kingdom |
| FG001 | Denosumab | Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
| Received Study Drug |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W. |
| BG001 | Denosumab | Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Presence of Bone Metastasis | Data are based on randomized strata. | Count of Participants | Participants |
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| Histology | Data are based on randomized strata. | Count of Participants | Participants |
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| Geographic region | Count of Participants | Participants |
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| Eastern Cooperative Oncology Group (ECOG) Performance Status | Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self- Care; 4 = Completely Disabled, no self-care, confined to bed or chair; 5 = Dead. | Count of Participants | Participants |
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| Time from Initial Diagnosis of NSCLC to Randomization | Mean | Standard Deviation | months |
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Overall Survival (OS) | Overall survival was calculated as the time from the date of randomization to the date of death from any cause. Participants last known to be alive were censored at the last contact date. | All randomized participants | Posted | Median | 95% Confidence Interval | months | From randomization until the end of study; median time on study was 9.64 months. |
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| Secondary | Correlation of Tumor Tissue RANK Expression With Overall Survival | To assess whether the treatment effect on overall survival was correlated with receptor activator of nuclear factor (NF)-κB (RANK) protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANK expression level and OS was evaluated using a Cox proportional hazard models that included RANK expression level stratified by the randomization stratification factors in the corresponding treatment group. | All randomized participants who had evaluable pre-treatment tumor RANK expression. | Posted | Number | 95% Confidence Interval | hazard ratio | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
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| Secondary | Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival | To assess whether the treatment effect on overall survival was correlated with RANK ligand (RANKL) protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANKL expression level and OS was evaluated using a Cox proportional hazard models that included RANKL expression level stratified by the randomization stratification factors in the corresponding treatment group. | All randomized participants who had evaluable pre-treatment tumor RANKL expression. | Posted | Number | 95% Confidence Interval | hazard ratio | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
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| Secondary | Objective Response Rate | Objective response rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) based on modified RECIST 1.1 achieved over the study duration. CR: Disappearance of all target and non target lesions, normalization of tumor marker levels and no new lesions. PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, disappearance of target lesions with persistence of one or more non-target lesions and/or maintenance of tumor marker levels above normal limits and no new lesions. Participants who underwent surgical resection while on study were not evaluated for response after the surgery. Participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non-responders. | Randomized participants with at least one baseline measurable lesion per modified RECIST 1.1. | Posted | Number | percentage of participants | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
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| Secondary | Correlation of Tumor Tissue RANK Expression With Objective Response Rate | To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANK protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANK expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANK expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported. | All randomized participants with at least one baseline measurable lesion per modified RECIST 1.1 who had evaluable pre-treatment tumor RANK expression. | Posted | Number | 95% Confidence Interval | odds ratio | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
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| Secondary | Correlation of Tumor Tissue RANKL Expression With Objective Response Rate | To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANKL protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity. The correlation between RANKL expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANKL expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported. | All randomized participants with at least one baseline measurable lesion per modified RECIST 1.1 who had evaluable pre-treatment tumor RANKL expression. | Posted | Number | 95% Confidence Interval | odds ratio | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
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| Secondary | Clinical Benefit Rate | Clinical benefit rate was defined as the percentage of participants with an objective response (CR or PR) or stable disease (SD) or better for at least 16 weeks achieved over the study duration. If a participant underwent surgical resection while on study, the participant was not evaluated for response after the surgery. Participants who did not meet the criteria for clinical benefit by the analysis cutoff date were considered as non-responders. | Randomized participants with at least one baseline measurable lesion per modified RECIST 1.1. | Posted | Number | percentage of participants | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
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| Secondary | Progression-free Survival (PFS) | Progression-free survival was defined as the time from randomization to the first observed disease progression per modified RECIST 1.1 criteria or death from any cause. Participants last known to be alive who did not experience disease progression were censored at their last imaging assessment date, last contact date if they were in the survival follow up phase, end of the study date, or the primary analysis cut-off date, whichever was first. If a participant underwent surgical resection while on study, the participant was censored at the last evaluable imaging assessment prior to the surgery. | All randomized participants | Posted | Median | 95% Confidence Interval | months | From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months. |
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| Secondary | Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing | Serum samples were analyzed for denosumab using enzyme-linked immunosorbent assay (ELISA) following a validated procedure. The lower limit of quantification for the assay was 20 ng/mL. | Randomized participants who received denosumab every 3 weeks with at least one valid denosumab concentration measurement. | Posted | Mean | Standard Deviation | ng/mL | Prior to dosing at day 8 and weeks 3, 6, 9, 12, 15, 18, 21 and 24. |
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| Secondary | Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing | Serum samples were analyzed for denosumab using enzyme-linked immunosorbent assay (ELISA) following a validated procedure. The lower limit of quantification for the assay was 20 ng/mL. | Randomized participants who received denosumab every 4 weeks with at least one valid denosumab concentration measurement. | Posted | Mean | Standard Deviation | ng/mL | Prior to dosing at day 8 and weeks 4, 8, 12, 16, 20 and 24 |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following criteria
Fatal adverse events include only deaths reported on the Adverse Event Case Report Form. | All randomized participants who received at least one dose of study drug (denosumab or placebo) | Posted | Number | participants | From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. |
|
From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively.
Data are included for all participants who received at least one dose of study drug.
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W. | 68 | 76 | 71 | 76 | ||
| EG001 | Denosumab | Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. | 129 | 145 | 139 | 145 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cardiac tamponade | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Coronary artery insufficiency | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hereditary angioedema | Congenital, familial and genetic disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal wall haematoma | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Condition aggravated | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Infusion site extravasation | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Gangrene | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Gastroenteritis shigella | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Lung abscess | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pleural infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Radiation oesophagitis | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| General physical condition abnormal | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Glomerular filtration rate decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Nutritional condition abnormal | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vertebral lesion | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Bronchial carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Lung adenocarcinoma stage IV | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Lung squamous cell carcinoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Lymphangiosis carcinomatosa | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Metastases to bone marrow | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Metastases to meninges | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Metastatic neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Non-small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Non-small cell lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Non-small cell lung cancer stage IV | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Consciousness fluctuating | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Depressed level of consciousness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Stroke in evolution | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Device issue | Product Issues | MedDRA 20.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Renal haemorrhage | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Laryngeal mass | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Laryngeal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Aortic thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Embolism venous | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Superior vena cava syndrome | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069448 | Denosumab |
| D000077211 | Zoledronic Acid |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| White or Caucasian |
|
| Others |
|
| No |
|
| Non-squamous |
|
| Western Europe |
|
| Rest of World |
|
| 1 (Restrictive but ambulatory) |
|
| OG001 | Denosumab | Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
|
|
|
| OG001 | Denosumab | Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
|
|
|
| Denosumab |
Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
|
|
|
| OG001 | Denosumab | Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
|
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| OG001 | Denosumab | Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
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| Denosumab |
Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W. |
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