Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers

PRIMARY OBJECTIVE: I. To identify the maximally tolerated dose of adavosertib (AZD1775) to be used in combination with radiation therapy for patients with esophageal/gastroesophageal junction (GEJ) cancer that is metastatic or inoperable and not eligible for definitive chemoradiation. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the efficacy of AZD1775 when administered in combination with radiation therapy by assessing changes in Ogilvie dysphagia score following treatment, time to second intervention for dysphagia, and overall survival. III. To identify biomarkers that are predictive for response to experimental therapy. OUTLINE: This is a dose escalation study of adavosertib. Patients undergo radiation therapy once daily (QD) 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib orally (PO) QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 weeks, every 3 months for 2 years, then every 6 months for 3 years.