PRIMARY OBJECTIVE:~I. To determine the maximally tolerated dose of papaverine (PPV) in combination with chemoradiation (CRT) and immunotherapy in patients with unresectable locally advanced (LA) non-small cell lung cancer (NSCLC).~SECONDARY OBJECTIVES:~I. To estimate the rates of primary tumor control, local control, time to local-regional progression, disease-free survival (DFS), and overall survival (OS). II. To assess whether blood oxygen level determination (BOLD) functional magnetic resonance imaging (MRI) studies can predict which patients may respond best to PPV + CRT, and detect changes in oxygenation before and after PPV administration.~III. To assess whether blood-based and tissue-based biomarkers can predict which patients may respond best to PPV + CRT.~OUTLINE: This is a dose-escalation study of PPV.~Patients receive PPV intravenously (IV) or subcutaneously (SC) and undergo 5 fractions of radiation therapy (RT) per week. Patients also receive paclitaxel IV over 1 hour and carboplatin IV once weekly (QW) over 1-6 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 month of completing CRT, patients with PD-L1 positive disease receive durvalumab IV every 2 weeks (Q2W) for 12 months.~After completion of the study treatment, patients are followed for 2 years at 1, 3, 6, 9, 12, 16, 20, and 24 months, then periodically for up to 5 years.
This phase I trial finds out the best dose, possible benefits and/or side effects of papaverine when given together with chemoradiation intreating patients with stage II-III non-small cell lung cancer. Papaverine targets mitochondrial metabolism to decrease the cancer growth process. Giving papaverine with chemoradiation may work best to treat patients with non-small cell lung cancer.