Sorafenib for Patients With Metastatic or Recurrent Esophageal and Gastroesophageal Junction Cancer
Condition: Esophageal Cancer; Gastroesophageal Junction Cancer
Intervention: Sorafenib, administered orally; CT/MRI
Intervention description: Sorafenib 400 mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days. The cycle start date will coincide with the physician visit date. Because of the potential need for physician visit scheduling to vary (due to both physician and patient issues), to avoid violation of, and deviation from, the protocol, these visits may vary by up to one to fourteen (1-14) days. A study diary will be completed by patients to ensure compliance with the study drug.; A CT (computerized tomography) or MRI (magnetic resonance imaging) scan of the chest and abdomen will be obtained at baseline, after the first four weeks of therapy, at eight weeks, and then every eight weeks there afterwith a scheduling window of up to one to fourteen (1-14) days. The same imaging modality performed at baseline (CT or MRI) will be repeated at subsequent imaging.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ESOPHAGUS; BAY 43-9006 (SORAFENIB); 09-016; Nexavar®.

Summary:

      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.
    

Eligibility criteria:

        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.