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
SUMMARY

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.

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

• 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

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

This content was sourced from clinicaltrials.gov

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