Combination Chemotherapy in Treating Patients With Colorectal Cancer and Resectable Metastases
Condition: Colorectal Cancer; Metastatic Cancer; Chemotherapy
MeSH terms: Colorectal Neoplasms; Neoplasm Metastasis
Study type: Interventional
Phase: Phase 3

Summary: 
      PURPOSE: This randomized phase III trial is studying two different combination chemotherapy
      regimens to compare how well they work in treating patients with colorectal cancer and
      resectable metastases.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the 2-year disease-free survival rate in patients treated with these regimens.

      Secondary

        -  Compare the 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.

        -  Compare the objective response rate, postoperative complication rate, and transfusing
           rate in patients having metastasis surgery,

        -  Determine the pharmacogenetics of these regimens in these patients.

      OUTLINE: This is a randomized, open-label, multicenter phase III study. Patients are
      stratified according to prior chemotherapy (perioperative vs postoperative), prior treatment
      (surgery only vs radiotherapy with or without surgery), and Blumgart score (0-1 vs 2-3 vs
      4-5). Patients are randomized to 1 of 2 treatment arms.

        -  Arm I (FOLFOX 4): Patients receive FOLFOX 4 combination chemotherapy comprising
           oxaliplatin 85mg/m² IV over 2 hours, leucovorin calcium IV over 2 hours, fluorouracil IV
           bolus /15min and fluorouracil continuously over 22 hours on day 1. Treatment repeats
           every 2 weeks for 12 courses in the absence of disease progression or unacceptable
           toxicity.

        -  Arm II (FOLFOX 7 and FOLFIRI): Patients receive FOLFOX 7 combination chemotherapy
           comprising high-dose oxaliplatin 130mg/m² IV over 2 hours and leucovorin calcium IV over
           2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Treatment repeats
           every 2 weeks for 6 courses in the absence of disease progression or unacceptable
           toxicity. Patients then receive FOLFIRI combination chemotherapy comprising irinotecan
           hydrochloride 180mg/m² IV over 30-90 minutes and leucovorin calcium and fluorouracil IV
           bolus /15min on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2.
           Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or
           unacceptable toxicity.

      Patients in both arms who have undergone prior resection of metastatic lesions may undergo
      surgery after 6 courses of chemotherapy or after chemotherapy is completed.

      Quality of life is assessed at baseline and after courses 4, 8, and 12.

      After completion of study treatment, patients are followed periodically for 5 years.

      PROJECTED ACCRUAL: A total of 284 patients will be accrued for this study.
    

Intervention name(s): oxaliplatin, folinic acid, fluorouracil; oxaliplatin, irinotecan, folinic acid, fluorouracil
Intervention type(s): Drug; Drug
Intervention description(s): folinic acid 200 mg/m² (day 1&2) oxaliplatin 85 mg/m² (day 1) bolus 5FU 400 mg/m² (day 1&2) continuous 5FU 600mg/m² (day 1 to 2); FOLFOX7 folinic acid 400 mg/m² (day 1) oxaliplatin 130 mg/m² (day 1) continuous 5FU 3000mg/m² (day 1 to 2)
FOLFIRI folinic acid 400 mg/m² (day 1) irinotecan 180 mg/m² (day 1) bolus 5FU 400 mg/m² (day 1) continuous 5FU 2400mg/m² (day 1 to 2)
Intervention MeSH terms: Leucovorin; Folic Acid; Fluorouracil; Oxaliplatin; Irinotecan; 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; resectable metastases