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

Phase 1

• Conditions: second-line therapy for patients with stage IV non-small cell lung cancer (squamous and non-squamous) with bone metastases; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001105-85-FR
• Lead Sponsor: Centre Hospitalier Annecy Genevois

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-27
• Last Update Posted: 30 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 86

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 < 1.5× normal (N), ALAT and ASAT <2.5× N or <5× N if hepatic metastases are present;
- Renal function (calculation of renal clearance and creatininemia 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;
- The men must use effective contraception during and up to 6 months after the treatment period;
- Subjects with cerebral metastases may be enrolled, provided that all lesions are controlled, and adequately treated by radiotherapy (stereotactic or not), craniotomy, or gamma knife therapy, with no evidence of progression, and have not required steroids for at least 2 months prior to enrolment. Carcinomatous meningitis is excluded regardless of clinical stability ;
- Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines;
- Patient affiliated or benefitting from the French national health insurance program (Sécurité Sociale).

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 69
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified