A Multicenter Phase II Study Evaluating Denosumab (XGEVA®) in Combination With Nivolumab (OPDIVO®) as Second-line Therapy for Patients With Stage IV Non-small-Cell Lung Cancer (Squamous and Non-squamous) With Bone Metastases: DENIVOS STUDY

Who is this study for? Adult patients with Non-Small Cell Lung Cancer
Status: Active, not recruiting
Location: See all (27) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2

Bone metastases are common in Non-Small Cell Lung Cancer (NSCLC). They most often occur during disease progression. It is thought that more than half of the patients with bone metastases will have at least 1 skeletal-related event (SRE, i.e. pathological fractures, medullary compression, analgesic radiotherapy, preventive and/or analgesic surgery and hypercalcemia). Expert and medical Society guidelines, notably European Society for Medical Oncology in 2014, then in 2016, recommended using anti-resorptive agents (bisphosphonates or denosumab) to prevent SREs, attenuate pain and improve the quality of life, and decrease the medical-economic impact of this major metastatic site. Denosumab was accorded marketing authorization in France in 2011 as an anti-resorptive agent for bone metastases to delay the occurrence of SREs in lung-cancer patients. Immunotherapy, notably immune-checkpoint inhibitors, like nivolumab (anti-programed death-1), has recently become an integral part of the therapeutic arsenal against NSCLCs. Nivolumab was accorded marketing authorization based on the phase III CHECKMATE 017 (squamous cell NSCLCs) and CHECKMATE 057 (non-squamous cell NSCLCs) trials versus docetaxel, after the phase II CHECKMATE 063 trial. The denosumab-nivolumab combination is commonly used in current practice but has not been evaluated prospectively. The aim of this trial is to evaluate the combination of denosumab and nivolumab in second line of NSCLC with bone metastases.

Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No

• Cytologically or histologically proven stage IV NSCLC

• 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

• For non-squamous cell NSCLC, patients without known activating epidermal growth factor receptor mutation, anaplastic lymphoma kinase (ALK) or reactive oxygen species (ROS)-1 translocation, or B-Raf proto-oncogene, serine/threonine kinase (BRAF V600) mutation

• 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.

• Eastern Cooperative Oncology Group Performance Status 0/1

• Estimated life-expectancy ≥12 weeks

• No prior malignant tumor during the previous 5 years, except for in situ carcinomas of the cervix or basal or squamous cell carcinomas of the skin adequately treated;

• Adequate organ function determined by laboratory analyses less than 7 days before inclusion:

• Normal hepatic function: bilirubin < 1.5× normal (N), alanine aminotransferase and aspartate aminotransferase <2.5× N or <5× N if hepatic metastases are present

• Renal function (renal clearance of creatinine at least ≥45 mL/min)

• Hematological function: absolute number of neutrophils ≥1.5×109/L and/or platelets ≥100×109/L, hemoglobin ≥8 g/dL

• Women of child-bearing age must use an effective contraceptive method and mechanical contraception during and up to 6 months after the end of treatment;

• Men must use effective contraception during and up to 6 months after the treatment period

• Patient with asymptomatic brain metastases (treated or not) OR symptomatic brain metastases but adequately treated and controlled at the time of enrolment (without or with corticotherapy ≤ 10mg/day), can be included. Carcinomatous meningitis is excluded regardless of clinical stability

• Subjects must have signed and dated an approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care

• Patient affiliated or benefitting from the French national health insurance program

Other Locations
CH du Pays d'Aix
Chu Angers
Centre Hospitalier de Beauvais
Centre Hospitalier Fleyriat
CHU Morvan - Institut de Cancérologie et d'Hématologie
CH Intercommunal
Ch Intercommunal Elbeuf Louvier Val de Reuil
CH Intercommunal des Alpes du Sud
Hôpital Robert Boulin
Chu Dupuytren
CH Marne La Vallée
Hopital Européen
Hopital Nord APHM
CH Meaux
Centre Catalan d'Oncologie
CH Annecy-Genevois
CHU Hôpital Pontchailloux
CHU Rouen
CHU La Réunion - Site de Bellepierre
Groupe Hospitalier Sud Réunion - CHU de la Réunion
Institut de Cancérologie de la Loire
CLCC Paul Strauss
Centre Hospitalier de Bigorre
CHITS Toulon Sainte-Musse
Hôpital d'Instruction des Armées Saint-Anne
Hôpital André Mignot Centre Hospitalier de Versailles
CH Villefranche sur Saone
Time Frame
Start Date: November 6, 2018
Estimated Completion Date: December 31, 2024
Target number of participants: 82
Experimental: Denosumab-nivolumab combination
Both drugs to be continued until progression or unacceptable toxicity and for a maximum of two years
Leads: Centre Hospitalier Annecy Genevois
Collaborators: French Lung Cancer Group

This content was sourced from clinicaltrials.gov

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