Non-Small Cell Lung CancerPhase 2NCT01951586
Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
A Phase 2 study testing Denosumab, Zoledronic acid and Standard Chemotherapy in people with Non-Small Cell Lung Cancer, run by Amgen at 74 sites in 10 countries.
Trial summary
This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Denosumab, Zoledronic acid and Standard Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 226 participants
- Where
- 74 sitesin 10 countries
- Study dates
- 31 Dec 2013to 28 Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
- Active dental or jaw condition which requires oral surgery
- Non-healed dental/oral surgery
- Planned invasive dental procedures for the course of the study.
Trial locations and contacts
74 sites in 10 countries.
74 sites in 10 countries
United States18 sites
Research Site
Alexandria, Louisiana, 71301
Research Site
Anaheim, California, 92801
Research Site
Bismarck, North Dakota, 58501
Research Site
Brewer, Maine, 04412
Research Site
Cincinnati, Ohio, 45267
Research Site
Detroit, Michigan, 48202
Research Site
Durham, North Carolina, 27710
Research Site
East Setauket, New York, 11733
Research Site
Fairhaven, Massachusetts, 02719
Research Site
Farmington, Connecticut, 06030-1628
Research Site
Goodyear, Arizona, 85338
Research Site
Hickory, North Carolina, 28602
Research Site
Long Beach, California, 90813
Research Site
Los Angeles, California, 90024
Research Site
Los Angeles, California, 90048
Research Site
Nashville, Tennessee, 37203
Research Site
Westminster, Maryland, 21157
Research Site
Winston-Salem, North Carolina, 27157
France10 sites
Research Site
Caen, 14076
Research Site
Dijon, 21079
Research Site
Nantes, 44202
Research Site
Paris, 75020
Research Site
Paris, 75475
Research Site
Paris, 75674
Research Site
Pessac, 33604
Research Site
Reims, 51056
Research Site
Saint-Quentin, 02321
Research Site
Tours, 37044
United Kingdom8 sites
Research Site
Bristol, BS2 8ED
Research Site
Exeter, EX2 5DW
Research Site
Glasgow, G42 9LF
Research Site
Guildford, GU2 7XX
Research Site
London, SE1 9RT
Research Site
London, W6 8RF
Research Site
Plymouth, PL6 8DH
Research Site
Preston, PR2 9HT
Canada7 sites
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Greater Sudbury, Ontario, P3E 5J1
Research Site
Kitchener, Ontario, N2G 1G3
Research Site
Montreal, Quebec, H2W 1S6
Research Site
Saint John, New Brunswick, E2L 4L2
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Toronto, Ontario, M9N 1N8
Australia6 sites
Research Site
Adelaide, South Australia, 5000
Research Site
Footscray, Victoria, 3011
Research Site
Kogarah, New South Wales, 2217
Research Site
Parkville, Victoria, 3050
Research Site
Wahroonga, New South Wales, 2076
Research Site
Wodonga, Victoria, 3690
Greece6 sites
Research Site
Athens, 11522
Research Site
Athens, 12462
Research Site
Heraklion, 71110
Research Site
Pátrai, 26504
Research Site
Thessaloniki, 54622
Research Site
Thessaloniki, 57010
Czechia5 sites
Research Site
Chomutov, 430 12
Research Site
Ostrava-Poruba, 708 52
Research Site
Pardubice, 532 03
Research Site
Prague, 180 81
Research Site
Ústí nad Labem, 401 13
Italy5 sites
Research Site
Monza (MB), 20900
Research Site
Orbassano (TO), 10043
Research Site
Pavia, 27100
Research Site
Roma, 00128
Research Site
Saronno VA, 21047
Netherlands5 sites
Research Site
's-Hertogenbosch, 5223 GZ
Research Site
Arnhem, 6815 AD
Research Site
Harderwijk, 3844 DG
Research Site
Tilburg, 5022 GC
Research Site
Zutphen, 7207 AE
Germany4 sites
Research Site
Berlin, 14165
Research Site
Großhansdorf, 22927
Research Site
Köln-Merheim, 51109
Research Site
Ulm, 89081
About this study
Official title: A Randomized, Double-blind, Multi-center Phase 2 Trial of Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.
Read the detailed description
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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Denosumab, Zoledronic acid, Placebo to Denosumab, Standard Chemotherapy, Placebo to Zoledronic Acid
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called XGEVA
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.
Zoledronic acidDrug
Also called Zometa
Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.
Placebo to DenosumabDrug
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 ChemotherapyDrug
Standard of care chemotherapy consisting of pemetrexed or gemcitabine in combination with cisplatin or carboplatin administered according to local practice.
Placebo to Zoledronic AcidDrug
Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Zoledronic acid; Drug: Placebo to Denosumab; Drug: Standard Chemotherapy |
| 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. Receives: Drug: Denosumab; Drug: Standard Chemotherapy; Drug: Placebo to Zoledronic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization until the end of study; median time on study was 9.64 months.
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
- life threatening
- requires in-patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event Treatment-related AEs include only TEAEs for which the investigator indicated there was a reasonable possibility they may have been caused by study drug.
Fatal adverse events include only deaths reported on the Adverse Event Case Report Form.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2013 (estimated)
- Study start31 Dec 2013
- Primary completion29 Jul 2016
- Study completion28 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01951586
- Sponsor's protocol ID
- 20120249
- Other IDs
- 2013-001662-42
- Status last verified
- Oct 2021
- First submitted
- 24 Sep 2013
- Last updated
- 25 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 34543941
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Multi-center Phase 2 Trial of Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01951586
- Acronym / sponsor ID
- 20120249
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 31 Dec 2013 (actual)
- Primary completion
- 29 Jul 2016 (actual)
- Study completion
- 28 Nov 2017 (actual)
- First posted
- 26 Sep 2013 (estimated)
- Results
- Posted 28 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Zoledronic acid, Drug: Placebo to Denosumab, Drug: Standard ChemotherapyParticipants 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 | Drug: Denosumab, Drug: Standard Chemotherapy, Drug: Placebo to Zoledronic AcidParticipants 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
- 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
Key exclusion criteria (8 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: XGEVAAdministered 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. | Drug | Denosumab |
| Zoledronic acidAlso: ZometaAdministered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy. | Drug | Placebo |
| Placebo to DenosumabAdministered 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. | Drug | Placebo |
| Standard ChemotherapyStandard of care chemotherapy consisting of pemetrexed or gemcitabine in combination with cisplatin or carboplatin administered according to local practice. | Drug | Denosumab, Placebo |
| Placebo to Zoledronic AcidAdministered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy. | Drug | Denosumab |
Primary outcome
Overall Survival (OS)
Time frame: From randomization until the end of study; median time on study was 9.64 months.
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.
10 secondary outcomes
Correlation of Tumor Tissue RANK Expression With Overall Survival
Time frame: 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
Time frame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Objective Response Rate
Time frame: 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
Time frame: 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
Time frame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Clinical Benefit Rate
Time frame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Progression-free Survival (PFS)
Time frame: 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
Time frame: 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
Time frame: Prior to dosing at day 8 and weeks 4, 8, 12, 16, 20 and 24
Number of Participants With Treatment-emergent Adverse Events
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34543941Peters 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
74 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab, Zoledronic acid and Standard Chemotherapy in people with Non-Small Cell Lung Cancer, run by Amgen at 74 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 74 sites in United States, France, United Kingdom, Canada, Australia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: From randomization until the end of study; median time on study was 9.64 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01951586, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2021.