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

Study Overview
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Brief Summary
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This randomized phase III study compares safety and efficacy of two sequence arms in advanced colorectal cancer: irinotecan and S-1 (IRIS) followed by oxaliplatin containing regimen (arm A), or l-leucovorin (l-LV), 5-FU and oxaliplatin (mFOLFOX6) followed by irinotecan containing regimen (arm B).

Detailed Description
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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

Official Title
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Irinotecan Combined With S-1( IRIS ) Followed by mFOLFOX6 Regimen Versus mFOLFOX6 Followed by IRIS Regimen in Advanced Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Campto, Topotesin
* Drug: TS-1
* Drug: L-Plat
* Drug: Isovorin
* Drug: 5-FU


Participation Criteria
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Eligibility Criteria
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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: Patients receiving blood transfusion, blood derivatives or granulocyte-colony stimulating factor within 7days prior to entering the study. Patients can not have oral intake Patients receiving Flucytosine treatment Patients with severe pleural effusion or ascites. Patients who have brown brain metastasis Patients with diarrhea 4 or more times per day Patients with active gastrointestinal bleeding. Patients with intestinal obstruction Patients with active infection. Patients with serious pulmonary disease (such as interstitial pneumonia, pulmonary fibrosis, pulmonary emphysema) 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). Patients with significant cardiac disease. Patients with active multiple cancer. Patients with neuropathy ≥ grade 2 Patients who are pregnant, are of childbearing potential, or breast-feeding. Patients with severe mental disorder. Patients with a history of serious allergic reaction. Judged to be ineligible for this protocol by the investigation. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>mFOLFOX6 （ → IRIS ( Irinotecan and S-1) ） | Drug: L-Plat<br>* Oxaliplatin (85mg/m2) Day 1, 15<br>* Other names: Oxaliplatin;Drug: Isovorin<br>* l-leucovorin (200mg/m2) Day 1, 15<br>* Other names: l-leucovorin;Drug: 5-FU<br>* 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.<br>* Other names: Fluorouracil;|
| Experimental: 2<br>IRIS ( Irinotecan and S-1 ) → mFOLFOX6 | Drug: Campto, Topotesin<br>* 100 mg/m2, IV (in the vein) on day 1,15 of each cycle.<br>* Other names: Irinotecan;Drug: TS-1<br>* S-1 Day1 14, everyday P.O.(Day 15 28 rest)<br>* Other names: S-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS of 1st line treatment |  | 2-years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS |  | 4-years | 
| objective tumor response |  | 1-year | 
| PFS of 2nd line treatment |  | 1-year | 
| safety |  | 4-years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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irinotecan, S-1, Oxaliplatin, l-leucovorin, Fluorouracil, Metastatic colorectal cancer, phase III