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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2013-001662-42-GB
• Date of registration: 02/10/2013
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• 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
• Date of first enrolment: 06/12/2013
• Target sample size: 216
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001662-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Czech Republic, European Union, Germany, Greece, Italy, Netherlands, United Kingdom, United States

Contacts

• Name: IHQ Medical Info – Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info – Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
• Adult subjects with histologically or cytologically confirmed stage IV NSCLC who provide a tumor sample and are planned to receive 4-6 cycles of platinum-doublet based chemotherapy
• Radiographically evaluable disease according to modified RECIST 1.1 criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 119
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 97

Exclusion criteria:
• Known presence of epidermal growth factor receptor (EGFR) mutation
• Known brain metastases
• Prior therapy for the treatment of NSCLC, except if for non-metastatic disease and was completed at least 6 months prior to randomization
• Planned to receive bevacizumab
• Subjects with sarcomatoid, carcinoid, and mesenchymal histologies
• More than 1 year of cumulative oral bisphosphonate usage prior to randomization
• More than 1 previous dose of IV bisphosphonate administration prior to randomization
• Significant dental/oral disease, including prior history or current
evidence of osteonecrosis/ osteomyelitis of the jaw
• Known sensitivity to any of the products to be administered during the study (eg, mammalian derived products, calcium, or vitamin D)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-small Cell Lung Cancer
MedDRA version: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: XGEVA
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Denosumab
CAS Number: 615258-40-7
Current Sponsor code: AMG 162
Other descriptive name: Immunoglobulin G2 Human Monoclonal Antibody to RANK Ligand
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Overall survival

Main Objective: To estimate the treatment effect of the combination of denosumab and
standard of care (SOC) versus SOC alone on overall survival (OS).

Timepoint(s) of evaluation of this end point: Primary analysis cut-off date is event-driven (i.e. when approximately 149 deaths occur)

Secondary Objective: To assess whether any relative benefit on OS from the combination of denosumab and SOC versus SOC alone in NSCLC is associated with tumor
RANK expression
• To assess whether any relative benefit on objective response(OR) from the combination of denosumab and SOC versus SOC alone in NSCLC is associated with tumor RANK expression
• To assess whether any relative benefit on OS from the combination of denosumab and SOC versus SOC alone in NSCLC is associated with tumor RANK ligand expression
• To assess whether any relative benefit on OR from the combination of denosumab and SOC versus SOC alone in NSCLC is associated with tumor
RANKL expression
• To estimate the treatment effect of the combination of denosumab and SOC versus SOC alone on:
o Objective response rate
o Clinical benefit rate
o Progression-free survival
• To assess serum denosumab trough levels
• To assess the safety and tolerability of denosumab compared with placebo in combination with standard of care therapy

Secondary Outcome(s)

Secondary end point(s): • Tumor tissue RANK expression in correlation with
o OS
o Objective response rate (complete response [CR] + partial response [PR]) based on modified RECIST 1.1
• Tumor tissue RANKL expression in correlation with
o OS
o Objective response rate (complete response [CR] + partial response [PR]) based on modified RECIST 1.1
• Objective response rate based on modified RECIST 1.1
• Clinical benefit rate ([all objective response] + [SD or better for at least 16 weeks]) based on modified RECIST 1.1
• PFS based on modified RECIST 1.1
• Serum denosumab trough levels
• Treatment-emergent adverse events

Timepoint(s) of evaluation of this end point: Primary analysis cut-off date is event-driven (i.e. when approximately 149 deaths occur)

Secondary ID(s)

20120249

2013-001662-42-DE

Source(s) of Monetary Support

Amgen Inc

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 07/12/2018
• Date Completed: 28/11/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-001662-42/results