Clinical trial NCT01951586: Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-09-26
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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:

  * Active dental or jaw condition which requires oral surgery
  * Non-healed dental/oral surgery
  * Planned invasive dental procedures for the course of the study.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until the end of study; median time on study was 9.64 months.
Secondary outcomes:
measure: Correlation of Tumor Tissue RANK Expression With Overall Survival
timeFrame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
measure: Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival
timeFrame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
measure: Objective Response Rate
timeFrame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
measure: Correlation of Tumor Tissue RANK Expression With Objective Response Rate
timeFrame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
measure: Correlation of Tumor Tissue RANKL Expression With Objective Response Rate
timeFrame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
measure: Clinical Benefit Rate
timeFrame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
measure: Progression-free Survival (PFS)
timeFrame: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.
measure: Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing
timeFrame: Prior to dosing at day 8 and weeks 3, 6, 9, 12, 15, 18, 21 and 24.
measure: Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing
timeFrame: Prior to dosing at day 8 and weeks 4, 8, 12, 16, 20 and 24
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 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.
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Farmington
country: United States
facility: Research Site
state: Connecticut
city: Alexandria
country: United States
facility: Research Site
state: Louisiana
city: Brewer
country: United States
facility: Research Site
state: Maine
city: Westminster
country: United States
facility: Research Site
state: Maryland
city: Fairhaven
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: East Setauket
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Hickory
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Bismarck
country: United States
facility: Research Site
state: North Dakota
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Kogarah
country: Australia
facility: Research Site
state: New South Wales
city: Wahroonga
country: Australia
facility: Research Site
state: New South Wales
city: Adelaide
country: Australia
facility: Research Site
state: South Australia
city: Footscray
country: Australia
facility: Research Site
state: Victoria
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Wodonga
country: Australia
facility: Research Site
state: Victoria
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Saint John
country: Canada
facility: Research Site
state: New Brunswick
city: Kitchener
country: Canada
facility: Research Site
state: Ontario
city: Sudbury
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Chomutov
country: Czechia
facility: Research Site
city: Ostrava-Poruba
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Usti nad Labem
country: Czechia
facility: Research Site
city: Caen Cedex 5
country: France
facility: Research Site
city: Dijon cedex
country: France
facility: Research Site
city: Nantes Cedex 2
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Paris Cedex 14
country: France
facility: Research Site
city: Paris Cedex 20
country: France
facility: Research Site
city: Pessac Cedex
country: France
facility: Research Site
city: Reims Cedex
country: France
facility: Research Site
city: Saint Quentin
country: France
facility: Research Site
city: Tours Cedex 9
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Köln-Merheim
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraklion
country: Greece
facility: Research Site
city: Patra
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Monza (MB)
country: Italy
facility: Research Site
city: Orbassano (TO)
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Saronno VA
country: Italy
facility: Research Site
city: 's Hertogenbosch
country: Netherlands
facility: Research Site
city: Arnhem
country: Netherlands
facility: Research Site
city: Harderwijk
country: Netherlands
facility: Research Site
city: Tilburg
country: Netherlands
facility: Research Site
city: Zutphen
country: Netherlands
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Exeter
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
city: Preston
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.