Combination Chemotherapy and Bevacizumab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, leucovorin, and
      fluorouracil, 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 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.
      Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

      PURPOSE: This randomized phase III trial is comparing two combination chemotherapy regimens
      given together with bevacizumab to see how well they work as first-line therapy in treating
      patients with metastatic colorectal cancer that cannot be removed by surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To compare the progression-free survival of bevacizumab in combination with oxaliplatin,
           irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFOXIRI) versus
           bevacizumab in combination with irinotecan hydrochloride, fluorouracil, and leucovorin
           calcium (FOLFIRI) in patients with unresectable, metastatic colorectal cancer.

      Secondary

        -  To evaluate the safety profile, including long-term adverse events of these regimens in
           these patients.

        -  To compare the overall response rate, duration of response, and secondary R0 surgery
           rates of metastases and overall survival between treatment arms.

        -  To evaluate potential surrogate markers predictive of bevacizumab activity.

      OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance
      status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center.
      Patients are randomized to 1 of 2 treatment arms.

        -  Arm I (FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin
           IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1.
           Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.

        -  Arm II (FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin
           calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil
           IV continuously over 48 hours beginning on day 1.

      In both arms, treatment repeats every 2 weeks for up to 12 courses. Treatment with
      bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease
      progression or unacceptable toxicity.

      Patients undergo serum extraction and blood sample collection periodically for genotyping
      studies. Patients also undergo collection of tumoral sections from paraffin embedded primary
      and/or metastatic lesions periodically for immunohistochemical analyses.

      After completion of study treatment, patients are followed every 8 weeks.
    

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