Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
Condition: Colorectal Cancer
MeSH terms: Colorectal 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. Bevacizumab may also stop the
      growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy
      work in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Giving bevacizumab together with combination chemotherapy may
      kill more tumor cells. It is not yet known which combination chemotherapy regimen is more
      effective when given together with bevacizumab in treating patients with colorectal cancer.

      PURPOSE: This randomized phase II trial is studying bevacizumab to compare how well it works
      when given together with two different combination chemotherapy regimens as first-line
      therapy in treating patients with metastatic colorectal cancer that cannot be removed by
      surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the progression-free survival at 6 months in patients with unresectable
           metastatic colorectal cancer treated with first-line therapy comprising bevacizumab and
           irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) vs bevacizumab
           and irinotecan hydrochloride and capecitabine (XELIRI).

      Secondary

        -  Compare the toxicities of these regimens in these patients.

        -  Compare the objective response rate and duration of response in patients treated with
           these regimens.

        -  Compare the tumor control in patients treated with these regimens.

        -  Compare the progression-free and overall survival of patients treated with these
           regimens.

        -  Compare the quality of life of patients treated with these regimens.

      OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified
      according to participating center, WHO performance status (0 or 1 vs 2), age (< 65 years vs ≥
      65 years), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2
      treatment arms.

        -  Arm I: Patients receive bevacizumab IV over 30-90 minutes, irinotecan hydrochloride IV
           over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV
           continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 12
           courses in the absence of disease progression or unacceptable toxicity. Patients may
           then continue to receive bevacizumab alone every 2 weeks in the absence of disease
           progression.

        -  Arm II: Patients receive bevacizumab IV over 30-90 minutes and irinotecan hydrochloride
           IV over 90 minutes on day 1 and oral capecitabine on days 1-14. Treatment repeats every
           3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
           Patients may then continue to receive bevacizumab alone every 3 weeks in the absence of
           disease progression.

      Quality of life is assessed periodically.

      After completion of study therapy, patients are followed periodically.

      PROJECTED ACCRUAL: A total of 144 patients will be accrued for this study.
    

Intervention name(s): bevacizumab; capecitabine; fluorouracil; irinotecan hydrochloride; leucovorin calcium
Intervention type(s): Biological; Drug; Drug; Drug; Drug
Intervention MeSH terms: Leucovorin; Bevacizumab; Capecitabine; Fluorouracil; Irinotecan; Calcium; Levoleucovorin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer