Combination Chemotherapy as First-Line Therapy in Treating Older Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and irinotecan, work
      in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Giving more than one drug (combination chemotherapy) in
      different doses or combinations may kill more tumor cells. It is not yet known which
      combination chemotherapy regimen is more effective in treating colorectal cancer.

      PURPOSE: This randomized clinical trial is studying how well fluorouracil works together with
      leucovorin with or without irinotecan in treating older patients with metastatic colorectal
      cancer .
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the progression-free survival of elderly patients with unresectable metastatic
           colorectal cancer treated with 1 of 2 different chemotherapy regimens comprising
           fluorouracil and leucovorin calcium with vs without irinotecan hydrochloride.

      Secondary

        -  Compare the tumor response rate and overall survival of patients treated with these
           regimens.

        -  Compare the tolerability of these regimens in these patients.

        -  Compare the quality of life of patients treated with these regimens.

      OUTLINE: This is a randomized, multicenter, prospective study. Patients are stratified
      according to participating center, gender, Karnofsky score (60-70% vs 80-90% vs 100%),
      associated comorbidities (Charlson Index 0 vs 1-2 vs 3+), age (75 to 79 years vs ≥ 80 years),
      alkaline phosphatase level (≤ 2 times normal vs > 2 times normal), and prior adjuvant
      chemotherapy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

        -  Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV
           continuously over 22 hours on days 1 and 2.

        -  Arm II: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV
           continuously over 46 hours on days 1 and 2.

        -  Arm III: Patients receive leucovorin calcium and fluorouracil as in arm I and irinotecan
           hydrochloride IV over 90 minutes on day 1.

        -  Arm IV: Patients receive leucovorin calcium and fluorouracil as in arm II and irinotecan
           hydrochloride as in arm III.

      In all arms, treatment repeats every 14 days in the absence of disease progression or
      unacceptable toxicity.

      Patients undergo surgery within 3-10 weeks after completing chemotherapy.

      Quality of life is assessed at baseline and then every 2 months thereafter.

      After completion of study treatment, patients are followed periodically.

      PROJECTED ACCRUAL: A total of 282 patients will be accrued for this study.
    

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