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)
- Conditions
- colorectal cancer
- Registration Number
- JPRN-UMIN000002388
- Lead Sponsor
- PO Epidemiological and Clinical Research Information Network
- Brief Summary
RESULTS: After a median follow-up period of 22 months, complete response was achieved in 1.9%, partial response in 38.5 %, stable disease in 51.9% and progressive disease in 3.9%. The overall response rate was 40.4%, the disease control rate was 92.3% and the median overall survival time was 22.3 months. The major toxicity was grade 3-4 neutropenia in 44.2%. There was no definite relation between UGT1A1 28, 6 polymorphisms and toxicity. However, homozygosity for UGT1A1 28 or UGT1A1 6 and double heterozygosity for both UGT1A1 28 and UGT1A1 6 were significantly associated with severe neutropenia in metastatic colorectal cancer patients (P< 0.001).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete: follow-up complete
- Sex
- All
- Target Recruitment
- 50
Not provided
(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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method (1)response rate (2)incidence and severity of adverse events
- Secondary Outcome Measures
Name Time Method (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).