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

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

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).

Study Overview

• Status: Suspended
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: L-Plat; Drug: Isovorin; Drug: 5-FU; Drug: Campto, Topotesin; Drug: TS-1

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8638
      • Hokkaido University Hospital (Hokkaido University Graduate School of Medicine / School of Medicine)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hokkaido Gastrointestinal Cancer Study Group
• Collaborators: Hokkaido University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Study Completion (ANTICIPATED): March 1, 2009

Study Registration Dates

• First Submitted: April 19, 2006
• First Submitted That Met QC Criteria: April 19, 2006
• First Posted (ESTIMATE): April 21, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): November 1, 2007
• Last Update Submitted That Met QC Criteria: October 31, 2007
• Last Verified: October 1, 2007

More Information

Terms related to this study

• Keywords: Fluorouracil; S-1; irinotecan; phase III; Oxaliplatin; Metastatic colorectal cancer; l-leucovorin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan
• Other Study ID Numbers: HGCSG0601; IFOX study