NIPH Clinical Trials Search

JAPANESE
国立保健医療科学院
UMIN ID: UMIN000000510

Registered date:01/11/2006

A genotype directed dose-finding study of Irinotecan (CPT-11) by groups of Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphisms in patients with advanced metastatic colorectal cancer and gastric cancer.

Basic Information

Recruitment status Complete: follow-up complete
Health condition(s) or Problem(s) studiedcolorectal cancer/ gastric cancer
Date of first enrollment2006/11/01
Target sample size80
Countries of recruitmentJapan
Study typeInterventional
Intervention(s)Administraion of CPT-11 is twice for 4 weeks on days 1 and 15. CPT-11 is reconstituted in >=250 mL of normal saline or 5% dextrose in water and infuse 90min on day 1 for pharmacokinetics, and 90min over on day15. CPT-11 adjusted dosage is determined from 50,75,100,125 or 150mg/sqm in the heterozygous group and the homozygous group by continual reassessment method. CPT-11 dosage is fixed at 150mg/sqm in the wild group.Definision of UGT1A1 polymorphisms groups: The homozygous group is patient with homozygous genotype of UGT1A1*28/*28 or UGT1A1*6/*6, with combined heterozygous genotypes of UGT1A1*28 and UGT1A1*6. The heterozygous group is patient with heterozygous genotype of either UGT1A1*28 or UGT1A1*6. The wild group is patients with no UGT1A1*28 and UGT1A1*6 mutation.

Outcome(s)

Primary OutcomeMaximum tolerated dose for the heterozygous group and the homozygous group, respectively. Incidence rate of dose limiting toxicities for the wild group.
Secondary OutcomeRecommended dose and dose limiting toxicity for heterozygous group and the homozygous groups, respectively. Incidence grade and frequency of toxicity. Pharmacokinetics of CPT-11, APC, SN-38 and SN-38G. Genetic polymorphisms analysis of UGT1A1,UGT1A7,UGT1A9 and OATP1B1 related to PK of CPT-11 and metabolites.

Key inclusion & exclusion criteria

Age minimum20years-old
Age maximumNot applicable
GenderMale and Female
Include criteria1)Histologically confirmed colorectal and gastric cancer 2)Metastatic colorectal cancer and locally advanced and/or metastatic gastric cancer 3)Testing confirmed UGT1A1*28 and UGT1A1*6 polymorphisms 4)Having prior chemotherapy as standard regimens 5)Wash out:>=14 days for operation, and >=21 days for chemotherapy and/or radiotherapy 6)No prior irinotecan containing treatment 7)Age:>=20 years old at wiritten informed concent 8)PS(ECOG):0 to 1 9)A life expectancy for at least 2 months 10)Aduquate main organ (bone marrow, heart, pulumonary, liver, renal) function (1)WBC 3,000-12,000/mm^3,(2)Neutrophil >=1500/mm^3,(3)Hb >=8.5mg/dL,(4)Platelet >=100,000/mm^3,(5)AST <=100IU/L,(6)ALT <=100IU/L,(7)T-bilirubin <=2.0mg/dL,(8)serum creatinine <=1.50mg/dL 11)Written informed consent
Exclude criteria1)History of serious drug allergy 2)Active concomitant malignancy 3)Prior extensively irradiation for abdominal or bowel bone marrow 4)Symptomatic brain metastasis 5)Systemic continual use of steroids 6)Active infection 7)Persistent diarrhea (watery stool) 8)Intestinal obstraction or paralytic ileus 9)Interstitial pneumonia or pulmonary fibrosis 10)Massive pleural, pericardial effusion or asites that required drainage 11)Need to treatment with atazanavir sulfate 12)Uncontrolled diabetes mellitus 13)Heart disease deemed to unacceptable by diagnosis of cardiogram within the previous 28 days before enrollment 14)Psychological disease deemed to unacceptable for inclusion to the study 15)Pregnant or lactating women, couple wishing pregnant or no mind of prevent pregnancy 16)Other concominant medical condition deemed to inadequate for inclusion to the study

Related Information

Contact

public contact
Name Shinji Sugimoto
Address 3F Ginza-Kobiki Bldg.,16-21,Ginza 7-chome, Chuo-ku, Tokyo,104-0061 JAPAN Japan
Telephone
E-mail shinji-sugimoto@yakult.co.jp
Affiliation Yakult Honsha Co.,Ltd Post Marketing Development, Pharmaceutical Department Department
scientific contact
Name Yuh Sakata
Address 1-10,Chuomachi 4-chome, Misawa City, Aomori,033-0051 JAPAN Japan
Telephone
E-mail
Affiliation Misawa City Hospital Internal medicine