Sorafenib is a drug being studied for the treatment of cancer. Sorafenib has been shown to block certain proteins on the surface of some cancer cells called "growth factor receptors." Blocking these growth factor receptors can slow or stop cancer cell growth.

Sorafenib is also known as Nexavar®. It has been studied in other types of cancers, including kidney cancer, and has been approved by the Food and Drug Administration (FDA) for treating advanced kidney cancer. Because it is not approved by the FDA for treating esophageal cancer, it is considered an experimental treatment.

The purpose of this study is to determine what effects sorafenib has on advanced esophageal cancer. These effects include whether sorafenib can shrink the tumor or slow down its growth and what side effects sorafenib will have on the tumor.

Inclusion Criteria:

• Patients must have histologically proven or cytologically confirmed esophageal cancer (squamous cell carcinoma or adenocarcinoma) or adenocarcinoma of the gastroesophageal (GE) junction documented at MSKCC.

• Metastatic disease measurable on a CT or MRI scan. Locally recurrent disease that is not amenable to potentially curative surgery or radiation therapy is also allowed. Lesions must be ≥ 10 mm in size. The primary tumor is not considered measurable disease. Recurrent or metastatic lesions within a prior radiation field are acceptable as long as disease has progressed in the radiation field by RECIST criteria. The same imaging modality performed at baseline (CT or MRI) will be repeated at subsequent imaging.

• Patients are allowed to have a maximum of two prior chemotherapy regimens for metastatic disease. Patients are allowed to have a maximum of three prior regimens if they also previously received neoadjuvant/adjuvant chemotherapy or chemoradiotherapy. The last treatment must have been administered > 3 weeks prior to initiation of therapy with sorafenib.

• Pathologic tissue must be available for immunohistochemistry (IHC) staining for phosphorylated extracellular signal-regulated kinase (pERK). Both patients with and without pERK staining are eligible for treatment. Submission of slides and IHC testing for pERK may be done during the course of therapy and are not required prior to protocol therapy.

• Age ≥ 18 years.

• Life expectancy > 3 months.

• Karnofsky performance status ≥ 60%.

• Patients must have the ability to comprehend and willingness to sign an informed consent document.

• At baseline, patients must have normal organ and marrow function as defined:

  • 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 ≤ 1.5 times ULN
    • ALT and AST ≤ 2.5 times the ULN ( < or = to 5 x ULN for patients with liver involvement)
    • Creatinine ≤ 1.5 times ULN

Exclusion Criteria:

• Patients who have not recovered from adverse events related to therapy administered > 3 weeks earlier. This does not include hemoglobin or other hematologic or laboratory criteria.
• Patients may not be receiving any other investigational agents.
• Prior therapy with sorafenib-related compounds or compounds of similar biologic or chemical components, including compounds targeting VEGF, VEGF-R or RAF kinase.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, greater than New York Heart Association (NYHA) Class II congestive heart failure, unstable or new onset angina pectoris or myocardial infarction within the past six months, unstable arrhythmia, or psychiatric illness/social situation, e.g., severe schizophrenia, that would limit compliance with study requirements. Patients with chronic arrhythmias, such as paroxysmal atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible.
• Uncontrolled hypertension, defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg, despite optimal medical management.
• Thrombotic or embolic event, including cerebrovascular accident or transient ischemic attack within the past six months. Patients with prior deep vein thromboses or pulmonary emboli on a stable anticoagulation regimen will be eligible for enrollment.
• Any factor that would significantly interfere with the inability to consume or absorb an oral medication, e.g. severe nausea/vomiting not controlled by an aggressive anti-emetic regimen, grade 3/4 dysphagia, extensive small bowel resection or active inflammatory bowel disease leading to chronic malabsorption. Patients with enteral feeding tubes are eligible as sorafenib can be crushed.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C infection.
• Patients with any other concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for participation in the study.
• Patients who are taking St. John's wort or rifampin (as there may be drug-drug interactions with sorafenib.
• Patients with known brain metastases or meningeal carcinomatosis are excluded. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Pregnant women are excluded because sorafenib has the potential for teratogenic or abortifacient effects. Female patients must either not be of childbearing potential or must have a negative pregnancy test ≤ 7 days prior to treatment. Female patients are considered not of childbearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or if they are post-menopausal. Men must use effective birth control if their partners are of child-bearing potential.
• No other malignancy is allowed except for adequately treated carcinoma in-situ of the cervix, superficial transitional cell carcinoma of the bladder or basal/squamous cell skin cancer. Other cancers are permissible if the patient has been disease free for ≥ 3 years.
• Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
• Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Known or suspected allergy to sorafenib or any agent given in the course of this trial.

Up to 2 years