Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
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
2 other identifiers
interventional
226
10 countries
74
Brief Summary
This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 nonsmall-cell-lung-cancer
Started Dec 2013
Typical duration for phase_2 nonsmall-cell-lung-cancer
74 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 24, 2013
CompletedFirst Posted
Study publicly available on registry
September 26, 2013
CompletedStudy Start
First participant enrolled
December 31, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 29, 2016
CompletedResults Posted
Study results publicly available
August 28, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 28, 2017
CompletedOctober 25, 2021
October 1, 2021
2.6 years
September 24, 2013
July 27, 2017
October 4, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
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.
Secondary Outcomes (10)
Correlation of Tumor Tissue RANK Expression With Overall Survival
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
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Objective Response Rate
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
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
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
- +5 more secondary outcomes
Study Arms (2)
Placebo
PLACEBO COMPARATORParticipants 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
EXPERIMENTALParticipants 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.
Interventions
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.
Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.
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 of care chemotherapy consisting of pemetrexed or gemcitabine in combination with cisplatin or carboplatin administered according to local practice.
Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (74)
Research Site
Goodyear, Arizona, 85338, United States
Research Site
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
Related Publications (1)
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.
PMID: 34543941BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Amgen Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 24, 2013
First Posted
September 26, 2013
Study Start
December 31, 2013
Primary Completion
July 29, 2016
Study Completion
November 28, 2017
Last Updated
October 25, 2021
Results First Posted
August 28, 2017
Record last verified: 2021-10