The purpose of this study is to determine whether nab-Paclitaxel (Abraxane®) and ramucirumab (Cyramza®) are effective when used in combination for treating patients with metastatic gastroesophageal cancer who have either progressed or not responded to prior therapy.

Adenocarcinoma of the esophagus and the gastroesophageal junction (GE junction) is the ninth most common cancer worldwide. Ramucirumab (Cyramza®), a monoclonal antibody, is approved as a single agent and in combination with paclitaxel as a treatment for patients with metastatic gastric or GE junction adenocarcinoma whose cancer has progressed after prior chemotherapy. Nab-paclitaxel (Abraxane®) is an albumin-based formulation of paclitaxel which was developed to improve the therapeutic index and reduce toxicity. Nab-paclitaxel is approved in over 40 countries/regions for treatment of various metastatic cancers including breast cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer. In this Phase II study, the investigators propose to combine the less toxic nab-paclitaxel to increase tumor uptake of the drug and improve efficacy while minimizing side effects. The biological rationale of using this combination is that ramucirumab will inhibit tumor angiogenesis and nab-paclitaxel will induce apoptosis of the rapidly dividing tumor cell.

Inclusion Criteria:

1. Patients with histologically confirmed metastatic adenocarcinoma of the esophagus, GE junction, or stomach who progressed on one prior line of chemotherapy in the metastatic setting.
2. Measurable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
4. Adequate hematologic, renal, and hepatic functions
5. Patients must have < Grade 2 pre-existing peripheral neuropathy (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v 4.03)
6. Life expectancy > 3 months

Exclusion Criteria:

1. Patients who have received any other investigational agents, chemotherapy, biologic therapy, or radiation therapy within the 28 days prior to Day 1 of the study. For investigational, chemotherapy, or biologic therapy, patients will be allowed on study if five half-lives or greater have elapsed since last dose of drug or 28 days, whichever is shorter.
2. Patients with prior taxane chemotherapy or agents which act by primary anti-angiogenic mechanisms.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results.
4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study initiation, or anticipation of need for major surgical procedure during the course of the study.
5. Evidence or history of uncontrolled hypertension, proteinuria, non-healing wound, ulcer, bone fracture, hemoptysis, valvular disease, abdominal fistula, GI perforation, intra-abdominal abscess, bleeding diathesis or coagulopathy that would exclude patients from treatment with anti-angiogenesis agents.
6. Therapeutic anticoagulation with coumarin-derivatives will not be permitted. However, a maximum daily dose of 1 mg will be permitted for port line patency. Anticoagulation with low molecular weight heparin or anti-Factor Xa agents will be allowed.
7. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise safety of treatment as so judged by treating physician (i.e., severely impaired lung function, severe infection, ventricular arrhythmias active ischemic heart disease, known active vasculitis of any cause, chronic liver or renal disease).