Randomized phase II trial of irinotecan(CPT-11) plus tegafur/uracil with oral leucovorin(UFT/LV) compared with FOLFIRI in patients with unresectable/recurrent colorectal cancer

UMIN ID: UMIN000000951

Registered date:19/12/2007

Basic Information

• Recruitment status: Complete: follow-up continuing
• Health condition(s) or Problem(s) studied: Patients with previously untreated and unresectable/recurrent colorectal cancer
• Date of first enrollment: 2007/11/01
• Target sample size: 72
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

UFT is administered orally at 300mg/m2/day with 75mg/day of oral leucovorin for 21 consecutive days followed by a 7 days rest. CPT-11 150mg/m2/day is given intravenously on day 1 and 15 of each cycle. Cycles are repeated every 4 weeks, until occuring disease progression or severe toxicities.
The administration is done on the 1st day and the 15th day of each cycle. Cycles are repeated every 4 weeks, until occuring disease progression or severe toxicities.FOLFIRI consisted of CPT-11 150 mg/m2 IV over 90 minutes, LV 400 mg/m2 IV over 2 hours, and FU 400 mg/m2 IV bolus, followed by FU 2.400mg/m2 IV over a 46-hour infusion, repeated every 2 weeks. Cycles are repeated every 4 weeks, until evidence of disease progression or severe toxicities.
UFT is administered orally at 300mg/m2/day with 75mg/day of oral leucovorin for 21 consecutive day followed by a 7 days rest. CPT-11 and Bevacizumab are given intravenously on day 1 and 15 of each cycle. Bevacizumab is added dilute to 100mL with physiological salt solution and given intravenously over 90 minutes. After the tolerability of the initial administration time is confirmed, the time can be shortened to 60 minutes. After the tolerability of the second administration time is confirmed, the time can be shortened to 90 minutes. After the administration of Bevacizumab, CPT-11 150mg/m2/day is given Cycles are repeated every 4 weeks, until occurring disease progression or severe toxicities Cycles are repeated every 4 weeks, until occurring disease progression or severe toxicities.
The administration is done on the 1st day and the 15th day of each cycle. Cycles are repeated every 4 weeks, until occurring disease progression or severe toxicities. Bevacizumab is added dilute to 100mL with physiological salt solution and given intravenously over 90 minutes. When the tolerability of the initial administration time is acceptable, then the time can be shortened to 60 minutes. After the tolerability of the second administration time is confirmed, the time can be shortened to 90 minutes. 5-FU and CPT-11 is given as follows. FOLFIRI consists of CPT-11 150 mg/m2 over 90 minutes, LV 400 mg/m2 over 2 hours, and FU 400 mg/m2 bolus, followed by FU 2.400mg/m2 over a 46-hours infusion, repeated every 2 weeks.

Outcome(s)

• Primary Outcome: Step1 Toxicity Step2 Progression-free survival
• Secondary Outcome: Step2 Response rate, toxicity, Time to treatment failure, overall survival

Key inclusion & exclusion criteria

• Age minimum: 20years-old
• Age maximum: 75years-old
• Gender: Male and Female
• Exclude criteria: 1)with history of myocardial infarction, drug hypersensitivity within 6 months prior to the registration. 2) Prior ventral irradiation for colorectal cancer. 3)with active infection. 4)with intestinal paralysis, intestinal obstruction, interstitial pneumonitis or pulmonary fibrosis, uncontrolled diabetes mellitus, cardiac failure, renal failure, liver dysfunction, which disturb registration to this study. 5) Massive pleural or ascites that required drainage. 6)with brain metastasis. 7)with diarrhea. 8)with active double cancer. 9)patients receiving Flucytosine or Atazanabil. 10)with mental disorder which disturbs registration to this study. 11)pregnant or nursing women or women who like be pregnant. 12)men with partner willing to get pregnant. 13)patients receiving analgesic drug or steroids. 14)doctor's decision not to be registered to this study. In addition to the above-mention, patients who hope to use Bevacizumab together has to be checked about the following factors. 1)Urine dipstick for proteinuria should be <2+ 2)Patient with a past history of thrombosis, cerebral infarction, myocardial infarction, or pulmonary embolism. 3)Major surgical procedure, open biopsy, or clinically significant traumatic injury within 4 weeks. 4) History of gastrointestinal perforation, intestinal tract paralysis, or ileus within 1 year. 5) Long-term daily treatment with aspirin (>325 mg/day) 6) History of evidence of bleeding tendency or coagulopathy or defect of coagulation factor (INR>=1.5) or patient who taking anticoagulant agent.

Related Information

• Primary Sponsor: Department of Surgery, School of Medicine, Keio University
• Source(s) of Monetary Support: None