Irinotecan, Cisplatin, Bevacizumab, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Esophageal Cancer
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
      ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others
      interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the
      growth of esophageal cancer by blocking blood flow to the tumor. Radiation therapy uses
      high-energy x-rays to kill tumor cells. Giving chemotherapy and monoclonal antibody therapy
      together with radiation therapy before surgery may make the tumor smaller and reduce the
      amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill
      any tumor cells that remain after surgery.

      PURPOSE: This phase II trial is studying how well giving irinotecan, cisplatin, and
      bevacizumab together with radiation therapy followed by surgery and bevacizumab works in
      treating patients with locally advanced esophageal cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Evaluate the toxicity and safety of bevacizumab when given together with cisplatin,
           irinotecan hydrochloride, and radiotherapy followed by surgery and adjuvant bevacizumab
           in patients with locally advanced esophageal adenocarcinoma.

      Secondary

        -  Observe the rate of pathologic complete response in patients treated with this regimen.

        -  Observe overall survival, disease-free survival, and patterns of failure in these
           patients.

        -  Clarify toxicity and tolerability of this regimen.

        -  Evaluate pre-treatment levels of vascular endothelial growth factor in patient serum as
           a corollary of response to this regimen.

        -  Correlate serum proteomics data with complete pathologic response.

      OUTLINE: This is a nonrandomized, open-label study.

        -  Induction therapy: Patients receive cisplatin IV over 30 minutes and irinotecan
           hydrochloride IV over 30 minutes on days 1, 8, 22, and 29. Patients also receive
           bevacizumab IV over 30-90 minutes on days 1 and 22.

        -  Combination therapy and radiotherapy: Patients receive cisplatin and irinotecan
           hydrochloride as in induction chemotherapy on days 43, 50, 64, and 71. Patients also
           receive bevacizumab IV over 30-90 minutes on days 43 and 64. Patients undergo external
           beam radiotherapy 5 days a week for 6 weeks beginning on day 43.

        -  Surgery: Patients undergo surgery 6-8 weeks after finishing combination therapy and
           radiotherapy.

        -  Maintenance therapy: Approximately 6 weeks after surgery, patients receive bevacizumab
           IV over 30-90 minutes every 3 weeks for 6 months.

      Blood samples are obtained at baseline, after finishing chemoradiotherapy, and prior to
      maintenance therapy and are examined by the matrix-assisted laser-desorption ionization time
      of flight (MALDI-TOF) mass spectometry for proteomic profiling.

      After completion of study treatment, patients are followed every 3 months for 1 year, every 4
      months for 1 year, every 6 months for 3 years, and then annually thereafter.
    

Intervention name(s): bevacizumab; cisplatin; irinotecan hydrochloride; proteomic profiling; diagnostic laboratory biomarker analysis; mass spectrometry; adjuvant therapy; neoadjuvant therapy; therapeutic conventional surgery; radiation therapy
Intervention type(s): Biological; Drug; Drug; Genetic; Other; Other; Procedure; Procedure; Procedure; Radiation
Intervention MeSH terms: Bevacizumab; Irinotecan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the esophagus; recurrent esophageal cancer; stage III esophageal cancer; stage II esophageal cancer