IRIS Followed by mFOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer

A multicenter randomized open-label controlled phase III study is conducted in patients with inoperable advanced or metastatic colorectal cancer who receive no previous chemotherapy. Usefulness of IRIS and mFOLFOX6 regimens as the 1st-line therapy for colorectal cancer is evaluated in PFS, MST, incidence and severity of adverse events

• Campto, Topotesin (Drug), also known as Irinotecan: 100 mg/m2, IV (in the vein) on day 1,15 of each cycle.
• TS-1 (Drug), also known as S-1: S-1 Day1\~14, everyday P.O.(Day 15\~28 rest)
• L-Plat (Drug), also known as Oxaliplatin: Oxaliplatin (85mg/m2) Day 1, 15
• Isovorin (Drug), also known as l-leucovorin: l-leucovorin (200mg/m2) Day 1, 15
• 5-FU (Drug), also known as Fluorouracil: 400 mg/m2, IV (in the vein) on day 1,15 of each 28 day cycle. 2400 mg/m2, CIV (in the vein) on day 1\~3 (48 hours) of each 28 day cycle.

Primary outcomes

• PFS of 1st line treatment [2-years]

Secondary outcomes

• OS [4-years]
• objective tumor response [1-year]
• PFS of 2nd line treatment [1-year]
• safety [4-years]

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1\. Histological diagnosis of colorectal cancer. 2） Age: 18 - 75 years. 3） No prior chemotherapy 4） ECOG Performance Status 0 to 2 5) A life expectancy of at least 3 months 6) Adequate function of major organs (bone marrow, heart, lungs, liver etc.). WBC ≧3,500/mm3 and Neutrophil ≧2,000/mm3. Hb ≧10.0 g/dl. Platelet count ≧100,000/mm3. AST and ALT ≦2.5 times the upper limit of normal (excluding liver metastasis). T-Bil ≦1.5 mg/dl. Creatinine ≦1.5 mg/ dl. 7).Patients must have the ability to understand and the willingness to sign a written informed contact document.

Exclusion Criteria:

1. Patients receiving blood transfusion, blood derivatives or granulocyte-colony stimulating factor within 7days prior to entering the study.
2. Patients can not have oral intake
3. Patients receiving Flucytosine treatment
4. Patients with severe pleural effusion or ascites.
5. Patients who have brown brain metastasis
6. Patients with diarrhea 4 or more times per day
7. Patients with active gastrointestinal bleeding.
8. Patients with intestinal obstruction
9. Patients with active infection.
10. Patients with serious pulmonary disease (such as interstitial pneumonia, pulmonary fibrosis, pulmonary emphysema)
11. Patients with serious complications (such as intestinal paralysis, intestinal obstruction, interstitial pneumonia or pulmonary fibrosis, uncontrolled diabetes mellitus, heart failure, renal failure, or hepatic failure).
12. Patients with significant cardiac disease.
13. Patients with active multiple cancer.
14. Patients with neuropathy ≥ grade 2
15. Patients who are pregnant, are of childbearing potential, or breast-feeding.
16. Patients with severe mental disorder.
17. Patients with a history of serious allergic reaction.
18. Judged to be ineligible for this protocol by the investigation.

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• Yoshito Komatsu, MD, PhD, Study chair, Hokkaido Gastrointestinal Cancer Study Group