second-line therapy for patients with stage IV non-small cell lung cancer (squamous and non-squamous) with bone metastases
Conditions
Interventions
Trade Name: XGEVA
Pharmaceutical Form: Suspension for injection
Trade Name: OPDIVO
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Centre Hospitalier Annecy Genevois
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - =18 years old; - Cytologically or histologically proven stage IV Non-Small Cell Lung Cancer; - ECOG PS 0/1; - For non-squamous cell Non-Small Cell Lung Cancer, patients without activating Epidermal Growth Factor-Receptor mutation, Anaplastic Lymphoma Kinase or ROS-1 translocation, or BRAF V600 mutation. - Patients who had received first-line platin salt-based chemotherapy and will be given second-line nivolumab; - Patients with bone metastases, symptomatic or not, confirmed by X-rays, CT scan, MRI, PET–CT scan or technetium bone scintigraphy; - Presence of at least 1 measurable target lesion, according to RECIST criteria 1.1, in a non-irradiated site; - PD-L1 status known and expressed as a percentage of tumor cells; assessed at the diagnosis or the more recent PD-L1 expression status available. - Estimated life-expectancy =12 weeks; - No prior malignant tumor during the previous 5 years, except for adequately treated in situ carcinomas of the cervix or basal or squamous cell carcinomas of the skin; - Adequate organ function determined by laboratory analyses less than 7 days before inclusion: - Normal hepatic function: bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: - Patients previously treated with bisphosphonates and/or denosumab; - Patients previously treated with immunotherapy; - Patients with symptomatic cerebral metastases; - Contraindication to nivolumab use: - Prior autoimmune disease(s), define as disease required systemic treatment in the past (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. - Prior diffuse interstitial pneumopathy, - Systemic immunosuppressive therapy; define as steroid medication at a dose greater than Prednisone 10 mg/day or equivalent. For patients with MMR-deficient high-grade gliomas, concurrent steroid medication at a dose greater than Prednisone 20mg/day or equivalent. - Contraindication for denosumab use: - Poor dental status requiring immediate specialized management, like oral surgery, - Prior or current signs of osteonecrosis of the jaw/osteomyelitis, - Invasive dental intervention schedule during the study or not yet healed; - Subject has known sensitivity to any of the products to be administered during the study - Concomitant administration of bisphosphonates; - Hypocalcemia or severe uncorrected hypercalcemia; - Medical or psychological condition preventing informed consent; - Pregnant or breastfeeding woman; - PD-L1–status results unavailable. - Simultaneous participation of the patients in another clinical research trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the Objective Response Rate (Complete Responses and Partial Responses) according to the PD-L1–expression rate (determined by immunohistochemistry and considered positive when =1% of the tumor cells are labeled) in Non-Small Cell Lung Cancer patients with bone metastases treated with the second-line denosumab–nivolumab combination.;Secondary Objective: - To evaluate, for the entire population, the disease-control rate (Complete Response, Partial Response, Stable Disease), the Objective Response Rate, the Overall Survival and progression-free survival; - To evaluate according to the PD-L1–expression level, the disease-control rate (Complete Response, Partial Response, Stable Disease), Overall Survival and progression-free survival; - To evaluate according to the histological type (adenocarcinoma vs. squamous cell), the disease-control rate (Complete Response, Partial Response, Stable Disease), the Objective Response Rate, the Overall Survival and progression-free survival; - To evaluate the time to the first Skeletal-Related Event; - To evaluate the toxicities of the association of Denosumab with Nivolumab. ;Primary end point(s): The Objective Response Rate according to the PD-L1 expression rate, defined as the number of treated patients having a Complete Response or Partial Response (according to RECIST 1.1 criteria) to treatment divided by the number of patients included.;Timepoint(s) of evaluation of this end point: Evaluation of this end point 7 weeks after the cycle 1 and then every 8 weeks +/- 5 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Disease Control Rate: percentage of patients with a Complete Response or Partial Response or Stable Disease, evaluated for the entire population, then according to the PD-L1–expression rate and histological type (adenocarcinoma vs squamous cell). - Objective Response Rate: percentage of patients with a Complete Response or Partial Response, evaluated for the entire population, then according to the histological type (adenocarcinoma vs squamous-cell). - Overall Survival at 24 months evaluated for the entire population, then according to the PD-L1–expression rate and histological type (adenocarcinoma vs squamous cell). - Progression-Free Survival at 24 months evaluated for the entire population, then according to the PD-L1–expression rate and histological type (adenocarcinoma vs squamous cell). - Time to the first Skeletal-Related Event in months. - The incidence of Adverse Events, severe Adverse Events, deaths and biological abnormalities scored according to NCI CTCAE V4.0 terminology. Prior Adverse Events and laboratory-test results will be recorded at inclusion then collected throughout the trial, notably at the start of each treatment cycle. ;Timepoint(s) of evaluation of this end point: - Evaluation of the Disease Control Rate (for the entire population, then according to the PD-L1–expression rate and histological type (adenocarcinoma vs squamous cell)) and the Objective Response Rate (for the entire population, then according to the histological type (adenocarcinoma vs squamous cell)): 7 weeks after the cycle 1 and then every 8 weeks +/- 5 days - Evaluation of the Overall Survival and the Progression-Free Survival for the entire population, then according to the PD-L1–expression rate and histological type (adenocarcinoma vs squamous cell) at 24 months - Evaluation of the Time to the first Skeletal-Related Event and toxicities according to NCI CTCAE V4.0 terminology at each cycle | — |
Countries
France
Contacts
Public ContactFlorence ENNAHDI
Centre Hospitalier Annecy Genevois
Outcome results
None listed