Bevacizumab, Combination Chemotherapy, and Radiation Therapy in Treating Patients Undergoing Surgery For Locally Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as
      gemcitabine, oxaliplatin, and fluorouracil, work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy
      uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with combination
      chemotherapy and radiation therapy may kill more tumor cells.

      PURPOSE: The phase II trial is studying the side effects and how well giving bevacizumab
      together with gemcitabine, oxaliplatin, fluorouracil, and radiation therapy works in treating
      patients undergoing surgery for locally advanced pancreatic cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To describe the toxicity of bevacizumab with gemcitabine and oxaliplatin, when therapy
           is given before chemoradiotherapy, in patients with locally advanced pancreatic cancer.

        -  To describe the toxicity of bevacizumab with oxaliplatin, fluorouracil, and concomitant
           radiotherapy in these patients.

        -  To define progression-free survival, time to progression, and overall survival of
           patients treated with this regimen.

      Second

        -  To determine the percentage of potentially resectable patients who are ultimately able
           to proceed to successful resection.

        -  To determine the relationship between markers of apoptosis in tumor cells (including
           MIF, CREB, HIF-1-alpha expression/polymorphism, and others) and response to therapy.

        -  To define response rates in patients treated with this regimen.

      OUTLINE:

        -  Neoadjuvant therapy: Patients receive gemcitabine IV over 100 minutes and bevacizumab IV
           over 30-90 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats
           every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable
           toxicity. Between 4-6 weeks after completion of initial therapy, patients undergo
           radiotherapy once daily, 5 days a week, for 5-6 weeks. Beginning within 48 hours after
           initiation of radiotherapy, patients receive fluorouracil IV continuously through
           completion of radiotherapy. Patients also receive concurrent oxaliplatin IV over 2 hours
           on days 1, 15 and 29 and bevacizumab IV on days 1 and 15.

        -  Surgery: Four to six weeks after completion of neoadjuvant therapy, patients undergo
           resection of the tumor. Patients with no evidence of disease progression and who undergo
           successful surgical intervention (i.e., R0 resection) proceed to adjuvant chemotherapy
           within the next 6-10 weeks.

        -  Adjuvant therapy: Patients receive gemcitabine and bevacizumab for 4 courses as in
           neoadjuvant therapy.

      Patients undergo collection of tumor tissue samples at the time of diagnosis, prior to
      treatment by endoscopic ultrasound or laparoscopy, or during surgical resection following
      neoadjuvant therapy. Paraffin-embedded tumor tissue specimens obtained at baseline are
      analyzed by immunohistochemistry to assess tumor vascularity and angiogenic activity. Tumor
      vascularity is assessed via immunostaining of tumor specimens with the pan-endothelial cell
      marker, anti-CD34, for evaluation of tumor blood vessels. Angiogenic activity is assessed by
      analyzing pERK1/2, Ki67, and the pericyte coverage index in tumor specimens. Patients also
      undergo blood collection to determine plasma levels of VEGF at 4 weeks prior to initial
      chemotherapy and bevacizumab, at up to 48 hours prior to chemoradiotherapy and bevacizumab,
      and at up to 48 hours prior to adjuvant chemotherapy and bevacizumab.

      After completion of study therapy, patients are followed every 2 months for the first year,
      and then every 3 months thereafter.
    

Intervention name(s): bevacizumab; fluorouracil; gemcitabine hydrochloride; oxaliplatin; immunohistochemistry staining method; laboratory biomarker analysis; conventional surgery; endoscopic biopsy; laparoscopy; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Other; Other; Procedure; Procedure; Procedure; Radiation
Intervention MeSH terms: Bevacizumab; Gemcitabine; Fluorouracil; Oxaliplatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV pancreatic cancer; recurrent pancreatic cancer