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.

UMIN ID: UMIN000000510

Registered date:01/11/2006

Basic Information

• Recruitment status: Complete: follow-up complete
• Health condition(s) or Problem(s) studied: colorectal cancer/ gastric cancer
• Date of first enrollment: 2006/11/01
• Target sample size: 80
• Countries of recruitment: Japan
• Study type: Interventional
• 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 Outcome: Maximum tolerated dose for the heterozygous group and the homozygous group, respectively. Incidence rate of dose limiting toxicities for the wild group.
• Secondary Outcome: Recommended 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 minimum: 20years-old
• Age maximum: Not applicable
• Gender: Male and Female
• Exclude criteria: 1)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

• Primary Sponsor: Yakult Honsha Co.,Ltd
• Source(s) of Monetary Support: Yakult Honsha Co.,Ltd