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Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer

NCT ID: NCT01951586

Last Updated: 2021-10-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

226 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-31

Study Completion Date

2017-11-28

Brief Summary

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This randomized phase 2 trial is studying the effect of adding denosumab to standard chemotherapy in the treatment of advanced lung cancer.

Detailed Description

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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

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Zoledronic acid

Intervention Type DRUG

Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.

Placebo to Denosumab

Intervention Type DRUG

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 Chemotherapy

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Denosumab

Intervention Type DRUG

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 Chemotherapy

Intervention Type DRUG

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

Placebo to Zoledronic Acid

Intervention Type DRUG

Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.

Interventions

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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.

Intervention Type DRUG

Zoledronic acid

Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.

Intervention Type DRUG

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.

Intervention Type DRUG

Standard Chemotherapy

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

Intervention Type DRUG

Placebo to Zoledronic Acid

Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.

Intervention Type DRUG

Other Intervention Names

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XGEVA Zometa

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Goodyear, Arizona, United States

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Anaheim, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Farmington, Connecticut, United States

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Alexandria, Louisiana, United States

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Brewer, Maine, United States

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Westminster, Maryland, United States

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Fairhaven, Massachusetts, United States

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Detroit, Michigan, United States

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East Setauket, New York, United States

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Durham, North Carolina, United States

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Hickory, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Bismarck, North Dakota, United States

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Cincinnati, Ohio, United States

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Nashville, Tennessee, United States

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Kogarah, New South Wales, Australia

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Wahroonga, New South Wales, Australia

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Adelaide, South Australia, Australia

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Footscray, Victoria, Australia

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Parkville, Victoria, Australia

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Wodonga, Victoria, Australia

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Edmonton, Alberta, Canada

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Saint John, New Brunswick, Canada

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Greater Sudbury, Ontario, Canada

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Kitchener, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Chomutov, , Czechia

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Ostrava-Poruba, , Czechia

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Pardubice, , Czechia

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Prague, , Czechia

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Ústí nad Labem, , Czechia

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Caen, , France

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Dijon, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Pessac, , France

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Reims, , France

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Saint-Quentin, , France

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Tours, , France

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Berlin, , Germany

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Großhansdorf, , Germany

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Köln-Merheim, , Germany

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Ulm, , Germany

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Athens, , Greece

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Athens, , Greece

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Heraklion, , Greece

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Pátrai, , Greece

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Thessaloniki, , Greece

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Thessaloniki, , Greece

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Monza (MB), , Italy

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Orbassano (TO), , Italy

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Pavia, , Italy

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Roma, , Italy

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Saronno VA, , Italy

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's-Hertogenbosch, , Netherlands

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Arnhem, , Netherlands

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Harderwijk, , Netherlands

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Tilburg, , Netherlands

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Zutphen, , Netherlands

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Bristol, , United Kingdom

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Exeter, , United Kingdom

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Glasgow, , United Kingdom

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Guildford, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Plymouth, , United Kingdom

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Preston, , United Kingdom

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Countries

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United States Australia Canada Czechia France Germany Greece Italy Netherlands United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 34543941 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2013-001662-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20120249

Identifier Type: -

Identifier Source: org_study_id