Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing: A Randomized Trial to Assess the Role of Irinotecan and Oxaliplatin in Advanced Colorectal Cancer
OBJECTIVES:
- Compare the efficacy of combination chemotherapy comprising fluorouracil (5-FU) with
leucovorin calcium (CF) and either irinotecan (CPT-11) or oxaliplatin vs standard
sequential single-agent therapy comprising 5-FU with CF followed by CPT-11 in patients
with unresectable metastatic colorectal cancer.
- Determine whether combination chemotherapy is best used as first-line therapy or
reserved for second-line therapy after progression on first-line single-agent therapy
in these patients.
- Compare the efficacy and toxicity of an irinotecan-containing regimen vs an
oxaliplatin-containing regimen in these patients.
- Compare the overall survival, progression-free survival, and quality of life of
patients treated with these regimens.
- Compare the safety and toxicity of these regimens in these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to one
of five treatment arms.
- Arm I (standard therapy): Patients receive first-line chemotherapy comprising
leucovorin calcium IV over 2 hours on day 1 followed by fluorouracil IV continuously
over 46 hours on days 1-2 every 14 days. Patients with progressive disease then receive
second-line therapy comprising irinotecan IV over 90 minutes on day 1 every 21 days.
- Arm II: Patients receive first-line chemotherapy as in arm I. Patients with progressive
disease then receive second-line therapy comprising irinotecan IV over 30 minutes and
leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46
hours on days 1-2 every 14 days.
- Arm III: Patients receive first-line chemotherapy comprising irinotecan, leucovorin
calcium, and fluorouracil as in second-line therapy of arm II.
- Arm IV: Patients receive first-line chemotherapy as in arm I. Patients with progressive
disease then receive second-line therapy comprising leucovorin calcium IV and
oxaliplatin IV over 2 hours on day 1 followed by fluorouracil IV continuously over 46
hours on days 1-2 every 14 days.
- Arm V: Patients receive first-line chemotherapy comprising leucovorin calcium,
oxaliplatin, and fluorouracil as in second-line therapy of arm IV.
Treatment continues in all arms in the absence of disease progression or unacceptable
toxicity.
Quality of life is assessed at baseline, at weeks 6 and 12, and then every 12 weeks
thereafter.
PROJECTED ACCRUAL: A total of 2,100 patients (700 in arm I and 350 each in arms II-V) will
be accrued for this study.
Interventional
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Matthew T. Seymour, MA, MD, FRCP
Study Chair
Medical Research Council
United States: Federal Government
CDR0000068372
NCT00008060
May 2000
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