Capecitabine With or Without Sunitinib Malate as First-Line Therapy in Treating Patients With Metastatic Cancer of the Esophagus or Gastroesophageal Junction
Condition: Adenocarcinoma of the Gastroesophageal Junction; Esophageal Cancer
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Intervention: capecitabine; sunitinib malate
Intervention description: Given orally; Given orally
Intervention MeSH terms: Capecitabine; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the esophagus; adenocarcinoma of the gastroesophageal junction; recurrent esophageal cancer; stage IV esophageal cancer; stage III esophageal cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth and by blocking blood flow to the tumor. It is not yet known whether
      capecitabine is more effective when given alone or together with sunitinib malate in treating
      patients with metastatic esophageal cancer or gastroesophageal junction cancer.

      PURPOSE: This randomized phase II trial is studying how well capecitabine works compared with
      capecitabine given together with sunitinib malate as first-line therapy in treating patients
      with metastatic cancer of the esophagus or gastroesophageal junction.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed adenocarcinoma of the esophagus or
             gastroesophageal junction

               -  Metastatic disease

               -  Unresectable disease with no curative options

          -  Measurable disease with ≥ 1 lesion whose longest diameter can be accurately measured
             as ≥ 2.0 cm by conventional techniques or ≥ 1.0 cm by spiral CT

          -  Not a candidate for a conventional multi-drug chemotherapy regimen with fairly
             standard dosing (i.e., patient is able to tolerate at least 80% of standard dosing)

               -  Patients who have been offered and declined conventional multi-drug chemotherapy
                  are eligible

          -  No known CNS metastases

        PATIENT CHARACTERISTICS:

          -  ECOG performance status (PS) 0-2 and age ≥ 65 years OR PS 2 and age ≥ 18 years but <
             65 years

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Total bilirubin normal

          -  Alkaline phosphatase ≤ 2 times upper limit of normal (ULN)

          -  Creatinine ≤ 1.5 times ULN

          -  Creatinine clearance ≥ 60mL/min

          -  AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Willing to provide tissue samples for central review and research purposes

          -  Able to swallow pills

          -  No immunocompromised patients (other than related to the use of corticosteroids),
             including patients known to be HIV-positive

          -  No co-morbid systemic illnesses or other severe concurrent disease that, in the
             judgment of the investigator, would make the patient inappropriate for this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  No uncontrolled intercurrent illness including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness or social situations that would limit compliance with study
                  requirements

          -  No NYHA class III or IV heart failure

          -  No uncontrolled hypertension except at the discretion of treating oncologist

          -  No other active malignancy except for nonmelanoma skin cancer or carcinoma in situ of
             the cervix

          -  No known dihydropyrimidine dehydrogenase deficiency (DPD)

        PRIOR CONCURRENT THERAPY:

          -  No prior chemotherapy, radiotherapy, immunotherapy, or biological therapy for
             recurrent or metastatic cancer

               -  Prior chemotherapy or radiotherapy are allowed if they had been administered as
                  adjuvant or neoadjuvant therapy and a complete surgical resection of the original
                  cancer had been achieved

          -  No prior sunitinib malate

          -  No prior radiotherapy to > 30% of the marrow cavity at any time

          -  More then 4 weeks since prior major surgery

          -  At least 12 days since prior and no concurrent CYP3A4 inducers, including rifampin,
             rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's wort, efavirenz, and
             tipranavir

          -  At least 7 days since prior and no concurrent CYP3A4 inhibitors, including azole
             antifungals (ketoconazole, itraconazole), clarithromycin, erythromycin, diltiazem,
             verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir,
             nelfinavir), and delavirdine

          -  No other concurrent specific treatment (other than hormonal therapy) in patients with
             a history of prior malignancy