Selumetinib and Paclitaxel as Second-Line Treatment in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVE: I. To determine the safety and tolerability of three pre-planned arms of continuous, intermittent, and pulsatile selumetinib with paclitaxel as second-line treatment in patients with stage IIIB or IV NSCLC. SECONDARY OBJECTIVE: I. To determine the preliminary clinical response of continuous, intermittent, and pulsatile selumetinib with paclitaxel as second-line treatment in patients with stage IIIB or IV NSCLC. EXPLORATORY OBJECTIVES: II. To determine progression-free survival (PFS) and overall survival (OS) in patients treated with selumetinib/paclitaxel. II. To assess correlations between cell-free deoxyribonucleic acid (DNA) (cfDNA) molecular features from blood and molecular features and pathways from the biopsy samples, and use this as a surrogate measure of tumor response and duration of response as evaluated in the primary and secondary objectives. OUTLINE: This is a dose-finding study of selumetinib. The goal is to find out what dose and dosing schedule is the most effective in this population. Patients are randomized to 1 of 3 treatment arms. ARM I: Patients receive selumetinib orally (PO) twice daily (BID) on days 1-21 and paclitaxel intravenously (IV) over a fixed rate on days 1 and 8. ARM II: Patients receive selumetinib PO BID on days 1-5, 8-12, and 15-19 and paclitaxel as in Arm I. ARM III: Patients receive selumetinib PO BID on days 1-3, 8-10, and 15-17 and paclitaxel as in Arm I. In all three arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing clinical benefit from study treatment may continue treatment based on the principal investigator (PI) approval on a patient-by-patient basis. After completion of study treatment, patients are followed up at 30 days, every 8 weeks for 12 months, and then every 3 months thereafter.