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Pre-Operative Programmed Death-1 (PD1) Checkpoint Blockade and Receptor Activator of NFkB Ligand (RANKL) Inhibition in Non-Small Cell Lung Cancer (NSCLC) (POPCORN) – a trial for patients with resectable NSCLC

ACTRN 12618001121257

Brief Summary

This study is designed to test the potential activity/benefit, safety and feasibility of adding a drug commonly used for bone protection (denosumab) to an immunotherapy drug (nivolumab) before surgery in patients with non-small cell lung cancer (NSCLC) for whom surgery has been recommended.

Intervention/Treatment

  • Drug: Nivolumab
  • Drug: Denosumab

Inclusion Criteria

  1. Histological or cytological diagnosis of NSCLC.
  2. Baseline histological specimen from primary tumor (and locoregional lymph node metastasis if clinically suspected) must be available for all patients.
  3. Primary tumor must be measurable on CT scan (RECIST v.1.1 criteria).
  4. Stage IA (>2cm) – IIIA confirmed by FDG-PET scan (it is strongly recommended that mediastinal nodal status in patients with N2 nodes is pathologically confirmed). Staging is according to 8th edition UICC/AJCC 2017.
  5. Considered to be surgically resectable by thoracic surgeon.
  6. No prior therapy for NSCLC.
  7. Age greater than or equal to 18 years.
  8. ECOG Performance Status 0-1.
  9. Peripheral neuropathy no worse than grade I.
  10. Patients on study with reproductive potential, or female partners with reproductive potential, must use an effective contraceptive method during the trial and for 3 months after the completion of chemotherapy.
  11. Adequate organ function including the following:
    • ­Expected FEV1 following surgery greater than or equal to 1.0 L/sec.
    • Adequate bone marrow reserve: ANC at least 1.5 x 109/L, platelets at least 100 x 109/L, haemoglobin at least 100 g/L.
    • Hepatic: bilirubin at least 1.5 times ULN; ALP, AST and/or ALT at least 3 times ULN.
    • Renal: creatinine clearance at least 60 mL/min (calculated). If the creatinine clearance is between 50 and 60 mL/min, then determination of glomerular filtration rate by nuclear medicine scan may be carried out and this result used for eligibility.
  12. Ability to give written informed consent.

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