A multicenter phase II study of FOLFIRI as first-line chemotherapy for metastatic colorectal cancer with reduced starting dose of irinotecan in patients with homozygous for UGT1A1(FLIGHT1)

UMIN ID: UMIN000002388

Registered date:01/09/2009

Basic Information

• Recruitment status: Complete: follow-up complete
• Health condition(s) or Problem(s) studied: colorectal cancer
• Date of first enrollment: 2005/11/01
• Target sample size: 50
• Countries of recruitment: Japan
• Study type: Interventional
• Intervention(s): On Day 1, patients treated with FOLFIRI therapy received a 2-hour intravenous infusion of CPT-11 (150 mg/m2) combined with 1-LV (200 mg/m2), followed by a rapid intravenous infusion of 5-FU (400 mg/m2), and then a 46-hour continuous infusion of 5-FU (2,400 mg/m2). This regimen comprised one course of therapy and was repeated once every 2 weeks. Cycles of treatment will be continued for this study until disease progression (PD) occurs. Patients will undergo UGT1A1 genotyping before starting to receive the protocol treatment. As recommended in the US prescribing information for Camptosar;, the starting dose of CPT-11 will be reduced to 100 mg/m2 in patients who are homozygous for the *28 allelic variant of UGT1A1 (further reduced to 75 mg/m2 in such patients aged 76-80 years). No dose adjustments will be made in patients who undergo UGT1A1 genotyping after starting to receive the protocol treatment.

Outcome(s)

• Primary Outcome: (1)response rate (2)incidence and severity of adverse events
• Secondary Outcome: (1) Determination of the time to response, the duration of response, the progression-free survival (PFS) time, and the overall survival (OS) time. (2) Evaluation of the causal relationship of each adverse event with the protocol treatment, its reversibility, its cumulative dose-response relationship, and its course over time. (3) Detection of genetic variation (when possible) and correlation of genetic variations with the pharmacokinetics of CPT-11, SN-38, and SN-38G as well as with the toxicities of CPT-11 (as an ancillary investigation).

Key inclusion & exclusion criteria

• Age minimum: 20years-old
• Age maximum: 80years-old
• Gender: Male and Female
• Exclude criteria: (1) Blood transfusion, administration of blood products, or hematopoietic (e.g., G-CSF) support within 7 days before enrollment. (2) A history of severe drug allergy. (3) Pleural effusion, ascites, or pericardial effusion requiring drainage. (4) Concurrent active (e.g., clinically significant) infection. (5) Confirmed or clinically suspected brain metastasis.*1 (6) Involvement of the central nervous system. (7) Presence of bone metastasis as the sole metastasis. (8) Any other concurrent malignancy, excluding metachronous malignancy that has been confirmed to have been cured.*2 (9) Uncontrolled hypercalcemia. (10) Uncontrolled hypertension (despite antihypertensive medication). (11) Uncontrolled diabetes mellitus. (12) Any significant electrocardiographic abnormality or clinically significant heart disease.*3 (13) Fresh gastrointestinal bleeding. (14) Intestinal paralysis or obstruction. (15) Diarrhea (watery stools).*4 (16) Positivity for HIV antibody. (17) Current treatment with atazanavir sulfate. (18) Current treatment with phenytoin, warfarin potassium, or flucytosine. (19) Pregnant or breast-feeding women, women of childbearing potential, women who wish to become pregnant, or men who wish to have a child with their female partners. (20) Current participation in any other clinical trial/study. (21) Any other condition that disqualifies the patient from the study in the opinion of the investigator.

Related Information

• Primary Sponsor: NPO Epidemiological and Clinical Research Information Network
• Source(s) of Monetary Support: NPO Epidemiological and Clinical Research Information Network