Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01951586