Combination Chemotherapy and Bevacizumab With or Without Bevacizumab Maintenance Therapy in Treating Patients With Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium,
      and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing
      the cells or by stopping them from dividing. Bevacizumab may stop the growth of colorectal
      cancer by blocking blood flow to the tumor. It is not yet known whether giving more than one
      drug (combination chemotherapy) is more effective when given with or without bevacizumab in
      treating patients with metastatic colorectal cancer.

      PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with or
      without bevacizumab to see how well it works in treating patients with metastatic colorectal
      cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare disease-control duration in patients with metastatic colorectal cancer receiving
           FOLFIRI chemotherapy in combination with bevacizumab with or without bevacizumab
           maintenance therapy.

      Secondary

        -  Determine objective response rate.

        -  Determine non-hematologic grade 3-4 (except alopecia) toxicity rate.

        -  Determine overall toxicity rate.

        -  Determine duration of chemotherapy-free interval.

        -  Determine progression-free survival.

        -  Determine overall survival.

        -  Determine time-to-treatment failure.

        -  Determine quality of life (EORTC QLQ-C30).

        -  Complete geriatric evaluation.

      OUTLINE: This is a multicenter study. Patients are stratified according to cancer center,
      primary tumor (resected vs unresected), and Köhne criteria (low vs intermediate vs high).
      Patients are randomized to 1 of 2 treatment arms.

        -  Arm A: Patients receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over
           90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46
           hours on days 1-2. Chemotherapy treatment repeats every 2 weeks for 12 courses. Patients
           also receive bevacizumab IV over 30-90 minutes once every 2 weeks during chemotherapy.
           Patients then receive bevacizumab maintenance therapy once every 2 weeks during the
           chemotherapy-free interval.

        -  Arm B: Patients receive FOLFIRI chemotherapy and bevacizumab as in arm A. Patients
           receive no treatment during the chemotherapy-free interval.

      In all arms, the chemotherapy treatment and the chemotherapy-free interval treatment repeats
      in the absence of disease progression during the chemotherapy portion or unacceptable
      toxicity. Patients who progress during the chemotherapy-free interval will receive 12 more
      courses of chemotherapy.

      All patients complete quality of life questionnaires (QLQ-30) and patients ≥ 75 also complete
      the geriatric questionnaire at baseline and every 8 weeks during study treatment.

      After completion of study treatment, patients are followed up every 8 weeks.
    

Intervention name(s): bevacizumab; FOLFIRI regimen; fluorouracil; irinotecan hydrochloride; leucovorin calcium
Intervention type(s): Biological; Drug; Drug; Drug; Drug
Intervention MeSH terms: Leucovorin; Bevacizumab; 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