Nintedanib Compared With Placebo in Treating Against Radiation-Induced Pneumonitis in Patients With Non-small Cell Lung Cancer That Cannot Be Removed by Surgery and Are Undergoing Chemoradiation Therapy

PRIMARY OBJECTIVES: I. To evaluate the safety of the combination of durvalumab with nintedanib in patients with unresectable Stage II/III/oligometastatic IV non-small cell lung carcinoma (NSCLC). (Phase I) II. To compare the rate of symptomatic radiation pneumonitis at 6 months after completion of chemoradiation in patients with unresectable stage II/III/ oligometastatic IV NSCLC who completed chemoradiation followed by nintedanib versus placebo. (Phase II) SECONDARY OBJECTIVES: I. To compare the quality of life (QOL) in patients who received nintedanib versus placebo during active treatment until 6 months after completion of treatment. II. To compare the progression-free survival, overall survival and 1-year progression-free survival rate in patients who received nintedanib versus placebo. III. To compare pulmonary function test (PFT) results and radiation pneumonitis (RP) score in patients who received nintedanib versus placebo. IV. To compare the composite index (based on PFT, RP score and QOL) at the end of active treatment and 6 months after completion of treatment between patients who received nintedanib versus placebo. EXPLORATORY OBJECTIVES: I. To investigate blood-based biomarkers in evaluating risk of developing radiation pneumonitis as well as the efficacy of nintedanib. OUTLINE: This is a phase I, dose-escalation study of nintedanib followed by a phase II study. Patients who are not receiving durvalumab as standard of care prior to establishment of the recommended phase II dose are randomized to 1 of 2 arms. Patients receiving durvalumab are assigned to Arm III. ARM I: Beginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Beginning 4-8 weeks after completion of radiation therapy, patients receive placebo capsules PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM III: Beginning 4-8 weeks after completion of radiation therapy, patients receive nintedanib PO BID on days 1-28 and standard of care durvalumab intravenously (IV) over 60 minutes on days 1 and 15. Treatment with nintedanib repeats every 28 days for up to 6 cycles and treatment with durvalumab repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, between 76-97 days, between 166-187 days, and then between 2.5 years.