Phase II Study of Diclofenac Salvage in Patients Metastatic Non-Small Cell Lung Cancer With Early Signs of Progression on Single Agent PD(L)-1 Blockade
This phase II trial tests how well diclofenac works in treating patients non-small cell lung cancer (NSCLC) that may have spread from where it first started (primary site) to other places in the body (metastatic) on single agent immunotherapy. Diclofenac, a type of non-steroidal anti-inflammatory (NSAID), blocks the body's production of a substance that causes inflammation and may decrease tumor growth and improve the effectiveness of immunotherapy. Immunotherapy with pembrolizumab, atezolizumab, nivolumab or cemiplimab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving diclofenac may kill more tumor cells in patients with metastatic NSCLC on single agent immunotherapy.
• Capable of signing informed consent
• Age ≥ 18 years at time of study entry
• Stage III or IV pathologically proven NSCLC with advanced or metastatic disease, currently on treatment with an Food and Drug Administration (FDA) approved single agent monoclonal antibody inhibiting the PD(L)-1 pathway (pembrolizumab, atezolizumab, nivolumab, or cemiplimab) for a minimum of 12 weeks
⁃ May include frontline single agent immune checkpoint inhibitors (ICI), maintenance single agent ICI after chemo-ICI, or subsequent line therapy
• Radiographic evidence of clinical progression as determined by the treating physician, not warranting immediate change of therapy. Progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria is not required. This can include mixed response, will need at least one growing lesion. Exposure to PD1 inhibitor for at least 12 weeks will minimize the risk of pseudo-progression
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy of ≥ 26 weeks
• Absolute neutrophil count (ANC) ≥ 1,000 cell/mm\^3
• Platelets ≥ 100,000 cells/mm\^3
• Hemoglobin ≥ 8 gm/dL
• Creatinine clearance ≥ 45 ml/ml
• Bilirubin ≤ 1.5 x institutional upper limit of normal
⁃ Bilirubin must be ≤ 3 x institutional upper limit of normal in patients with documented Gilbert's syndrome
• Serum glutamic oxaloacetic transaminase (SGOT) / serum gluatmic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal
• Ability to take oral medications
• Willingness and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up