advanced NSCLC MedDRA version: 17.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 100000004864
Conditions
Interventions
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
Other descriptive name: DENOSUMAB
Con
Sponsors
ETOP (European Thoracic Oncology Platform)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically or cytologically confirmed advanced stage IV non-small cell lung carcinoma (NSCLC), according to 7th TNM classification - Age = 18 years - ECOG performance status 0-2 - Measurable or evaluable disease (according to RECIST 1.1 criteria) - Availability of tumour tissue for translational research: - preferred: FFPE block from primary tumour or metastasis, - alternatively: cell block - if no block available: 10 unstained slides with wax protection - Adequate haematological function: neutrophils = 1.5 ×109/L, platelets = 100×109/L, and hemoglobin = 9 g/dL - Adequate liver function: - ALT = 3 × ULN ( = 5 × ULN if liver metastasis are present) - Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 450
Exclusion criteria
Exclusion criteria: - Patients with presence of documented sensitizing EGFR activating mutation or ALK rearrangements (screening following local standards is optional, but strongly encouraged in non-squamous histology) - Patients with documented brain metastases (systematic screening of patients not mandatory) - Prior chemotherapy or molecular targeted therapy for metastatic disease, with the exception of neoadjuvant or adjuvant chemotherapy or definitive radiochemotherapy, if terminated more than 6 months before registration. - Any investigational agent(s) within 30 days prior to randomisation - Concurrent bisphosphonate administration - Oral/ dental conditions (by visual inspection): - Prior history or current evidence of osteomyelitis / osteonecrosis of the jaw - Active dental or jaw condition which requires oral surgery - Planned invasive dental procedure for the course of the trial - Non-healed dental or oral surgery - Evidence of any medical condition which would impair the ability of the patient to participate in the trial or might preclude therapy with trial drugs (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, active infection, uncontrolled diabetes mellitus; uncontrolled arterial hypertension = 150/100 mmHg, history of myocardial infarction in the last 3 months) - Documented active infection with Hepatitis B virus or Hepatitis C virus, known infection with human immunodeficiency virus (HIV) - Known hypersensitivity to any of the components of the treatment - Severe, uncorrected hypocalcaemia or hypercalcaemia - hypercalcaemia: total calcium >3.1 mmol/l, corrected calcium (with albumin level) >3 mmol/l - hypocalcaemia: total calcium <2 mmol/l, corrected calcium (with albumin level) < 1.9 mmol/l - Legal incapacity or limited legal capacity - Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the trial or sign meaningful informed consent - Women who are pregnant or breastfeeding - Any concurrent malignancy other than adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma. (Patients with a previous malignancy but without evidence of disease for = 2 years will be allowed to enter the trial) - Any previous exposure to denosumab, with the exception of a maximum of 2 previous doses of denosumab (Prolia®) more than 6 month before enrolment for osteoporosis treatment/prevention - Previous bisphosphonate exposure which - exceeds 2 prior doses of i.v. bisphosphonates AND/OR - exceeds a cumulative exposure of 1 year oral bisphosphonates
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether the addition of denosumab to standard firstline chemotherapy in advanced NSCLC improves overall survival.;Secondary Objective: - to compare progression free survival (PFS) and response rate (RR, based on RECIST 1.1) in patients treated with standard first-line chemotherapy with or without denosumab - to assess the tolerability of the two regimens - to evaluate potential predictive biomarkers for denosumab activity;Primary end point(s): Overall survival ;Timepoint(s) of evaluation of this end point: Time from the date of randomisation until death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-free survival (PFS) based on RECIST 1.1 - Response based on RECIST 1.1 - Toxicity profile of denosumab - Evaluation of potential predictive biomarkers for denosumab activity;Timepoint(s) of evaluation of this end point: - PFS: time from date of randomisation until objective disease progression or death, whichever occurs first - Response of the tumour is defined according to RECIST 1.1 criteria - Toxicity profile of denosumab: Adverse events classified according to NCI CTCAE V4 - Evaluation of potential predictive biomarkers for denosumab activity: collection of tumor at randomisation and collection of serum samples at baseline, at dady 1 of cycles 3 and at first progression | — |
Countries
Austria, Belgium, Bulgaria, France, Germany, Ireland, Israel, Italy, Poland, Romania, Slovenia, Spain, Switzerland, United Kingdom
Contacts
Public ContactETOP Coordinating Office
ETOP
Outcome results
None listed