Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Denosumab; Zoledronic acid; Placebo to Denosumab; Standard Chemotherapy; Placebo to Zoledronic Acid
Intervention description: Administered by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8; could be administered as often as every 3 weeks (Q3W) to participants receiving Q3W chemotherapy.; Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.; Administered by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8; could be administered as often as every 3 weeks (Q3W) to participants receiving Q3W chemotherapy.; Standard of care chemotherapy consisting of pemetrexed or gemcitabine in combination with cisplatin or carboplatin administered according to local practice.; Administered by intravenous infusion in participants with bone metastasis upon investigative site request for IV bone-targeted therapy.
Intervention MeSH terms: Zoledronic Acid; Denosumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 226.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

Summary:

      This randomized phase 2 trial is studying the effect of adding denosumab to standard
      chemotherapy in the treatment of advanced lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed stage IV non-small cell lung carcinoma
             (NSCLC), according to 7th Tumor/Node/Metastasis (TNM) classification (cytological
             specimens obtained by bronchial washing or brushing, or fine-needle aspiration are
             acceptable)

          -  Subject has available and has provided consent to release to the sponsor (or designee)
             a tumor block with confirmed tumor content (or approximately 20 unstained charged
             slides [a minimum of 7 slides is mandatory]) and the corresponding pathology report

          -  Planned to receive 4 to 6 cycles of pemetrexed or gemcitabine in combination with
             cisplatin or carboplatin

             • For subjects to receive pemetrexed, planned to receive vitamin B12 and folate per
             pemetrexed approved labeling

          -  Radiographically evaluable (measurable or non-measurable) disease (according to
             modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria

          -  Other inclusion criteria may apply

        Exclusion Criteria:

          -  Known presence of documented sensitizing epidermal growth factor receptor (EGFR)
             activating mutation or echinoderm microtubule-associated protein-like 4-anaplastic
             lymphoma kinase (EML4-ALK) translocation (screening following local standards, but
             strongly encouraged in non-squamous histology)

          -  Known brain metastases (systematic screening of patients not mandatory)

          -  Any prior systemic therapy (before randomization) for the treatment of NSCLC
             (including chemoradiation), except if for non-metastatic disease and was completed at
             least 6 months prior to randomization

          -  Planned to receive bevacizumab

          -  Significant dental/oral disease, including prior history or current evidence of
             osteonecrosis/ osteomyelitis of the jaw, or with the following:

               -  Active dental or jaw condition which requires oral surgery

               -  Non-healed dental/oral surgery

               -  Planned invasive dental procedures for the course of the study.