Phase II/III Trial of CPT-11/5-FU/l-LV Versus CPT-11/TS-1 as Second Line Chemotherapy of Unresectable Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT00284258
• Recruitment Status: Completed
• First Posted: January 31, 2006
• Last Update Posted: November 2, 2012
• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Collaborator: Daiichi Sankyo Co., Ltd.
• Information provided by (Responsible Party): Taiho Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: January 30, 2006
• First Posted Date: January 31, 2006
• Last Update Posted Date: November 2, 2012
• Study Start Date: January 2006
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 2, 2008): Progression free survival [ Time Frame: every course for first three courses, then every other course ]
• Original Primary Outcome Measures (submitted: January 30, 2006): Progression free survival
• Current Secondary Outcome Measures (submitted: July 2, 2008): Over all survival, Response rate, Adverse event, Medical economy [ Time Frame: adverse events will be collected during treatment ]
• Original Secondary Outcome Measures (submitted: January 30, 2006): Over all survival, Response rate, Adverse event, Medical economy
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase II/III Trial of CPT-11/5-FU/l-LV Versus CPT-11/TS-1 as Second Line Chemotherapy of Unresectable Colorectal Cancer
• Official Title: Phase II/III Trial of CPT-11/5-FU/l-LV (FOLFIRI) Versus CPT-11/TS-1 (IRIS) as Second Line Chemotherapy of Unresectable Colorectal Cancer
• Brief Summary: This study is designed as Phase II/III. Phase II is aimed to evaluate safety and efficacy of IRIS, and feasibility of FOLFIRI. Phase III is aimed to verify inferiority of the progression free survival of IRIS in comparison with FOLFIRI.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: CPT-11 and TS-1
  TS-1 was administered orally at 40-60 mg twice daily for 14 days with a rest period of 14 days as one course. CPT-11 was administered intravenously 125 mg per square meter at day1 and day14 in 4 weeks as one course.
• Drug: CPT-11, 5-FU and l-LV
  Patients were administered FOLFIRI every 2 weeks in one course. FOLFIRI:CPT-11 150 mg per square meter on day1 with l-LV 200 mg per square meter administered as a 2-hour infusion before 5-FU 400 mg per square meter administered as an intravenous bolus injection, and 5-FU 2400 mg per square meter as a 46-hour infusion immediately after 5-FU bolus injection on day1 in 2 weeks.

Study Arms

• Experimental: 1
  CPT-11 and TS-1
  Intervention: Drug: CPT-11 and TS-1
• Active Comparator: 2
  CPT-11, 5-FU and l-LV
  Intervention: Drug: CPT-11, 5-FU and l-LV

Publications *

• Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, Satoh T, Denda T, Ina K, Nishina T, Yamaguchi K, Takiuchi H, Esaki T, Tokunaga S, Kuwano H, Komatsu Y, Watanabe M, Hyodo I, Morita S, Sugihara K. Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol. 2010 Sep;11(9):853-60. doi: 10.1016/S1470-2045(10)70181-9. Epub 2010 Aug 12.
• Yasui H, Muro K, Shimada Y, Tsuji A, Sameshima S, Baba H, Satoh T, Denda T, Ina K, Nishina T, Yamaguchi K, Esaki T, Tokunaga S, Kuwano H, Boku N, Komatsu Y, Watanabe M, Hyodo I, Morita S, Sugihara K. A phase 3 non-inferiority study of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer: updated results of the FIRIS study. J Cancer Res Clin Oncol. 2015 Jan;141(1):153-60. doi: 10.1007/s00432-014-1783-3. Epub 2014 Aug 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 1, 2012): 426
• Original Enrollment (submitted: January 30, 2006): 400
• Actual Study Completion Date: August 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed colorectal cancer
• Locally advanced and/or metastatic colorectal cancer
• Have prior chemotherapy as first line treatment
• No prior irinotecan administration
• Able to take oral medication
• Age 20 to 75
• Performance status 0 or 1 (ECOG)
• WBC 3,000-12,000 / mm^3
• Platelet ≥100,000 / mm^3
• AST and ALT ≤ 100 IU/L
• Creatinine ≤ 1.2 mg/dL
• Bilirubin ≤ 1.5 mg/dL

Exclusion Criteria:

• Prior radio therapy for colorectal cancer
• Other malignancies in the past 5 years
• Serious illness or medical condition

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00284258
• Other Study ID Numbers: 01023010 / TOP-003
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Taiho Pharmaceutical Co., Ltd.
• Original Responsible Party: Not Provided
• Current Study Sponsor: Taiho Pharmaceutical Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Daiichi Sankyo Co., Ltd.

Investigators

• Principal Investigator: Kenichi Sugihara, MD, PhD; Tokyo Medical and Dental University Hospital

• PRS Account: Taiho Pharmaceutical Co., Ltd.
• Verification Date: November 2012