Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: 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. Monoclonal antibodies,
      such as cetuximab, 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. It is not yet known whether giving combination chemotherapy together with
      intermittent cetuximab is more effective than combination chemotherapy given together with
      continuous cetuximab in treating colorectal cancer.

      PURPOSE: This randomized phase II trial is studying giving combination chemotherapy together
      with intermittent cetuximab to see how well it works compared to combination chemotherapy
      given together with continuous cetuximab as first-line therapy in treating patients with
      advanced or metastatic colorectal cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To compare the activity, in terms of failure-free survival, of patients with
           K-ras-normal (wild type) advanced and/or metastatic colorectal cancer treated with
           intermittent combination chemotherapy comprising oxaliplatin, leucovorin calcium, and
           fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) and intermittent vs
           continuous cetuximab as first-line therapy.

        -  To compare the safety and feasibility of these regimens in these patients.

      Secondary

        -  To compare the safety of cetuximab reintroduction, in terms of frequency of grade 3-4
           allergic reactions in these patients.

        -  To compare improvement in disease control (i.e., complete response plus partial response
           plus stable disease) at 24 weeks in patients treated with these regimens.

        -  To compare overall and progression-free survival of patients treated with these
           regimens.

        -  To compare response rates at 12, 24, and 36 weeks in patients treated with these
           regimens.

        -  To compare toxicity of these regimens in these patients.

      OUTLINE: This is a multicenter study. Patients are randomised to 1 of 2 treatment arms.

        -  Arm I (intermittent chemotherapy and intermittent cetuximab): Patients receive 1 of the
           following combination chemotherapy and cetuximab regimens:

             -  OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over
                2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2.
                Patients also receive cetuximab IV over 1-2 hours on days 1 and 8. Treatment
                repeats every 14 days for up to 6 courses (12 weeks) in the absence of disease
                progression or unacceptable toxicity.

             -  XELOX (for patients with line-related problems): Patients receive oxaliplatin IV
                over 2 hours on day 1 and oral capecitabine twice daily on days 1-15 (28 doses).
                Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment
                repeats every 21 days for up to 4 courses (12 weeks) in the absence of disease
                progression or unacceptable toxicity.

      After completion of 12 weeks of study therapy, patients with disease progression are removed
      from study. Patients with stable or responding disease stop treatment with OxMdG or XELOX and
      cetuximab and undergo clinical evaluation at least every 6 weeks until disease progression or
      clinical deterioration. Upon evidence of disease progression or clinical deterioration,
      patients restart treatment with OxMdG or XELOX and cetuximab as before and continue to
      alternate 12 weeks of treatment with treatment breaks in the absence of disease progression
      or unacceptable toxicity. Patients with disease progression during study therapy stop
      treatment and proceed to second-line therapy or best supportive care.

        -  Arm II (intermittent chemotherapy and continuous cetuximab): Patients receive OxMdG or
           XELOX and cetuximab for 12 weeks as in arm I. Patients with disease progression after 12
           weeks of study therapy are removed from study. Patients with stable or responding
           disease* after 12 weeks of study therapy stop treatment with OxMdG or XELOX and continue
           treatment with cetuximab weekly as monotherapy in the absence of disease progression or
           unacceptable toxicity. Patients undergo clinical evaluation as in arm I. Upon
           progression, patients restart treatment with OxMdG or XELOX and continue cetuximab, as
           before, alternating 12 weeks of combined OxMdG or XELOX and cetuximab therapy with
           cetuximab monotherapy. Patients with disease progression during study therapy stop
           treatment and proceed to second-line therapy as in arm I.

      Previously collected tumor tissue samples are obtained at baseline and analyzed by IHC for
      EGFR status of tumor.

      After completion of study treatment, patients are followed every 12 weeks.

      Peer Reviewed and Funded or Endorsed by Cancer Research UK.
    

Intervention name(s): cetuximab; capecitabine; fluorouracil; leucovorin calcium; oxaliplatin; immunohistochemistry staining method; laboratory biomarker analysis
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Other; Other
Intervention MeSH terms: Leucovorin; Capecitabine; Fluorouracil; Oxaliplatin; Cetuximab; Calcium; Levoleucovorin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the colon; stage IV colon cancer; adenocarcinoma of the rectum; stage IV rectal cancer; stage III colon cancer; stage III rectal cancer; recurrent colon cancer; recurrent rectal cancer