Leucovorin and Fluorouracil With or Without Oxaliplatin Compared to Capecitabine With or Without Oxaliplatin 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 leucovorin, fluorouracil, capecitabine, and
      oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or
      die. Combining more than one drug may kill more tumor cells. It is not yet known whether
      leucovorin and fluorouracil with or without oxaliplatin is more effective than capecitabine
      with or without oxaliplatin in treating patients who have metastatic colorectal cancer.

      PURPOSE: This randomized phase III trial is studying four different chemotherapy regimens to
      compare how well they work in treating patients with metastatic colorectal cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the progression-free survival of patients with metastatic colorectal
           adenocarcinoma treated with leucovorin calcium and fluorouracil with vs without
           oxaliplatin or capecitabine with vs without oxaliplatin.

        -  Compare the quality of life of patients treated with these fluorouracil-based vs
           capecitabine-based regimens.

      Secondary

        -  Compare the failure-free and overall survival of patients treated with these regimens.

        -  Compare the toxic effects and adverse events associated with these regimens in these
           patients.

        -  Compare the limited health assessments of patients treated with these regimens.

        -  Compare the health economics associated with these regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment
      arms and receive 12 weeks of therapy.

        -  Arm I (MdG regimen): Patients receive leucovorin calcium IV over 2 hours on day 1 and
           fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 14 days for up
           to 6 courses in the absence of disease progression or unacceptable toxicity.

      Patients with disease progression during or within 8 weeks of the completion of this regimen
      may cross over and receive second-line therapy on arm II.

        -  Arm II (OxMdG regimen): Patients receive leucovorin calcium IV over 2 hours and
           oxaliplatin IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day
           1. Treatment repeats every 14 days for up to 6 courses in the absence of disease
           progression or unacceptable toxicity.

      Patients with disease progression during or within 8 weeks of the completion of this regimen
      may receive second-line therapy or supportive care off-study.

        -  Arm III (Cap regimen): Patients receive oral capecitabine twice daily on days 1-15.
           Treatment repeats every 21 days for up to 4 courses in the absence of disease
           progression or unacceptable toxicity.

      Patients with disease progression during or within 8 weeks of the completion of this regimen
      may cross over and receive second-line therapy on arm IV.

        -  Arm IV (OxCap regimen): Patients receive oxaliplatin IV over 2 hours on day 1 and oral
           capecitabine twice daily on days 1-15. Treatment repeats every 21 days for up to 4
           courses in the absence of disease progression or unacceptable toxicity.

      Patients with disease progression during or within 8 weeks of the completion of this regimen
      may receive second-line therapy or supportive care off-study.

      All patients are then re-evaluated at least every 6 weeks and begin another 12 weeks of
      therapy at any evidence (e.g., clinical, radiological, or tumor marker) of disease
      progression. Patients with chemo-sensitive disease may repeat alternating 12-week therapy
      sessions and evaluation periods indefinitely.

      Quality of life is assessed at baseline, at 12-14 weeks, at 24 weeks, and then every 3 months
      thereafter.

      Patients are followed every 3 months.

      Peer Reviewed and Funded or Endorsed by Cancer Research UK

      PROJECTED ACCRUAL: A total of 460 patients (115 per treatment arm) will be accrued for this
      study within 2 years.
    

Intervention name(s): FOLFOX regimen; capecitabine; fluorouracil; leucovorin calcium; oxaliplatin; quality-of-life assessment
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Leucovorin; Capecitabine; Fluorouracil; Oxaliplatin; Calcium; Levoleucovorin
Allocation: Randomized
Intervention model: Single Group Assignment
Primary purpose: Treatment
Keywords: adenocarcinoma of the colon; adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; recurrent rectal cancer; recurrent colon cancer