Nintedanib in Patients With Advanced Esophagogastric Cancer
Condition: Esophagogastric Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Nintedanib
Intervention description: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.
Intervention MeSH terms: Nintedanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Nintedanib; 14-094

Summary:

      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.
    

Eligibility criteria:

        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.