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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01951586




Registration number
NCT01951586
Ethics application status
Date submitted
24/09/2013
Date registered
26/09/2013
Date last updated
25/10/2021

Titles & IDs
Public title
Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
Scientific 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
Secondary ID [1] 0 0
2013-001662-42
Secondary ID [2] 0 0
20120249
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Denosumab
Treatment: Drugs - Zoledronic acid
Treatment: Drugs - Placebo to Denosumab
Treatment: Drugs - Standard Chemotherapy
Treatment: Drugs - Placebo to Zoledronic Acid

Placebo Comparator: Placebo - 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.

Experimental: 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 with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.


Treatment: Drugs: Denosumab
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.

Treatment: Drugs: Zoledronic acid
Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.

Treatment: Drugs: Placebo to Denosumab
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.

Treatment: Drugs: Standard Chemotherapy
Standard of care chemotherapy consisting of pemetrexed or gemcitabine in combination with cisplatin or carboplatin administered according to local practice.

Treatment: Drugs: Placebo to Zoledronic Acid
Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization until the end of study; median time on study was 9.64 months.
Secondary outcome [1] 0 0
Correlation of Tumor Tissue RANK Expression With Overall Survival
Timepoint [1] 0 0
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Secondary outcome [2] 0 0
Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival
Timepoint [2] 0 0
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Secondary outcome [3] 0 0
Objective Response Rate
Timepoint [3] 0 0
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Secondary outcome [4] 0 0
Correlation of Tumor Tissue RANK Expression With Objective Response Rate
Timepoint [4] 0 0
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Secondary outcome [5] 0 0
Correlation of Tumor Tissue RANKL Expression With Objective Response Rate
Timepoint [5] 0 0
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Secondary outcome [6] 0 0
Clinical Benefit Rate
Timepoint [6] 0 0
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Secondary outcome [7] 0 0
Progression-free Survival (PFS)
Timepoint [7] 0 0
From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
Secondary outcome [8] 0 0
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing
Timepoint [8] 0 0
Prior to dosing at day 8 and weeks 3, 6, 9, 12, 15, 18, 21 and 24.
Secondary outcome [9] 0 0
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing
Timepoint [9] 0 0
Prior to dosing at day 8 and weeks 4, 8, 12, 16, 20 and 24
Secondary outcome [10] 0 0
Number of Participants With Treatment-emergent Adverse Events
Timepoint [10] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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:

- Active dental or jaw condition which requires oral surgery

- Non-healed dental/oral surgery

- Planned invasive dental procedures for the course of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/11/2017
Sample size
Target
Accrual to date
Final
226
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Research Site - Kogarah
Recruitment hospital [2] 0 0
Research Site - Wahroonga
Recruitment hospital [3] 0 0
Research Site - Adelaide
Recruitment hospital [4] 0 0
Research Site - Footscray
Recruitment hospital [5] 0 0
Research Site - Parkville
Recruitment hospital [6] 0 0
Research Site - Wodonga
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2076 - Wahroonga
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3011 - Footscray
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment postcode(s) [6] 0 0
3690 - Wodonga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Maine
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
North Dakota
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
New Brunswick
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Czechia
State/province [18] 0 0
Chomutov
Country [19] 0 0
Czechia
State/province [19] 0 0
Ostrava-Poruba
Country [20] 0 0
Czechia
State/province [20] 0 0
Pardubice
Country [21] 0 0
Czechia
State/province [21] 0 0
Praha 8
Country [22] 0 0
Czechia
State/province [22] 0 0
Usti nad Labem
Country [23] 0 0
France
State/province [23] 0 0
Caen Cedex 5
Country [24] 0 0
France
State/province [24] 0 0
Dijon cedex
Country [25] 0 0
France
State/province [25] 0 0
Nantes Cedex 2
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 10
Country [27] 0 0
France
State/province [27] 0 0
Paris Cedex 14
Country [28] 0 0
France
State/province [28] 0 0
Paris Cedex 20
Country [29] 0 0
France
State/province [29] 0 0
Pessac Cedex
Country [30] 0 0
France
State/province [30] 0 0
Reims Cedex
Country [31] 0 0
France
State/province [31] 0 0
Saint Quentin
Country [32] 0 0
France
State/province [32] 0 0
Tours Cedex 9
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Grosshansdorf
Country [35] 0 0
Germany
State/province [35] 0 0
Köln-Merheim
Country [36] 0 0
Germany
State/province [36] 0 0
Ulm
Country [37] 0 0
Greece
State/province [37] 0 0
Athens
Country [38] 0 0
Greece
State/province [38] 0 0
Heraklion
Country [39] 0 0
Greece
State/province [39] 0 0
Patra
Country [40] 0 0
Greece
State/province [40] 0 0
Thessaloniki
Country [41] 0 0
Italy
State/province [41] 0 0
Monza (MB)
Country [42] 0 0
Italy
State/province [42] 0 0
Orbassano (TO)
Country [43] 0 0
Italy
State/province [43] 0 0
Pavia
Country [44] 0 0
Italy
State/province [44] 0 0
Roma
Country [45] 0 0
Italy
State/province [45] 0 0
Saronno VA
Country [46] 0 0
Netherlands
State/province [46] 0 0
's Hertogenbosch
Country [47] 0 0
Netherlands
State/province [47] 0 0
Arnhem
Country [48] 0 0
Netherlands
State/province [48] 0 0
Harderwijk
Country [49] 0 0
Netherlands
State/province [49] 0 0
Tilburg
Country [50] 0 0
Netherlands
State/province [50] 0 0
Zutphen
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Bristol
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Exeter
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Glasgow
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Guildford
Country [55] 0 0
United Kingdom
State/province [55] 0 0
London
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Plymouth
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Preston

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT01951586
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries