This is a phase II study of Nintedanib in patients with metastatic or recurrent esophagogastric cancer. The goal of the study is to evaluate the efficacy of Nintedanib, an orally available triple kinase inhibitor targeting the receptors of the vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) receptor pathways.

Inclusion Criteria:

• Pathologically or cytologically MSKCC confirmed esophagogastric adenocarcinoma.
• Metastatic diseases measurable or evaluable on a CT or MRI scan according to RECIST 1.1 criteria. Locally recurrent disease that is not amenable to potentially curative surgery or radiation therapy is also allowed. Lesions must be ≥10mm in size. Recurrent or metastatic disease within a prior radiation field is acceptable as long as the disease has progressed in the radiation field by RECIST criteria.
• Patients are allowed to have had a maximum of 1 prior chemotherapy regimen for metastatic disease. Patients are allowed to have a maximum of two prior regimens if they previously received neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for their initial localized disease.
• Patients aged 18 years or older.
• Life expectancy of at least 6 months.
• Karnofsky Performance Status (KPS) performance score ≥ 70%.
• Patients must be able to reliably take and swallow oral medications.
• Patients with prior deep vein thrombosis (DVT) or pulmonary embolism (PE) currently on anticoagulation regimen will be permitted.
• Adequate bone marrow, liver, and renal function as assessed by the following:
• Hemoglobin ≥ 9.0 g/dL.
• Absolute neutrophil count (ANC) ≥ 1,500/mm3.
• Platelet count ≥ 100,000/mm3.
• Total bilirubin within normal limits, 0-1 mg/dL.
• AST and ALT< 1.5 times ULN. (For patients with liver involvement: AST and ALT≤ 2.5 ULN).
• International normalized ratio (INR) < 2, prothrombin time (PT) < 20 sec, and partial thromboplastin time (PTT) < 55 sec .
• Creatinine < 1.5 x the ULN or GFR<45 ml/min.

Exclusion Criteria:

• HER-2 positive esophagogastric cancer. Patients with unknown HER2 status are permitted.
• Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating esophagogastric cancer. Last prior therapy must have been completed at least 2 weeks (14 days) prior to starting Nintedanib.
• Concurrent radiotherapy is not permitted for disease progression on treatment on protocol. However, symptomatic treatment for pre-existing non-target lesions would be allowed with approval from the principal investigator.
• Prior treatment with VEGFR inhibitor.
• Brain metastases or leptomeningeal disease.
• History of arterial thromboembolic (arterial blood clot) or hemorrhagic event with the exception of patients with pulmonary embolism stable on an anticoagulation regimen.
• Patients with a cerebrovascular accident or transient ischemic attack within the past six months.
• Patients on warfarin for any reason.
• Patient with known pre-existing interstitial lung disease.
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure, New York Heart Association (NYHA) functional classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 month prior to the study entry.
• Patients with history of proteinuria grade ≥ 2.
• Women of childbearing potential (WOCBP), or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial and for at least three months after the end of active therapy.
• Women who are pregnant or breast-feeding. Persistence of clinically relevant therapy related toxicity from previous chemotherapy and/or radiotherapy. This does not include hemoglobin or other hematologic or laboratory criteria, as long as eligibility criteria are met
• Other malignancies within the past 5 years other than non-melanoma superficial skin cancer or carcinoma in situ of the cervix.
• Concurrent medical conditions or injury which may increase the risk of toxicity, including ongoing or active infection, history of significant bleeding disorder unrelated to cancer (congenital bleeding disorders, acquired bleeding disorders within one year), history of HIV-positive, or active or chronic hepatitis C and/or B infection.
• Known or suspected active drug or alcohol abuse.
• Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug. Patients who are unable to orally swallow the study medication.
• Known hypersensitivity to trial drug.

3 years