Sorafenib for Patients With Metastatic or Recurrent Esophageal and Gastroesophageal Junction Cancer

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 ( 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.
• Patien