NCT01523431

Individual Dosage Selection of Irinotecan (CPT-11) Based on UGT1A1 Genotype in Metastatic Colorectal Cancer Patients

Influence of Individual Dosage Selection of Irinotecan (CPT-11) Based on UGT1A1 Genotype on Clinical Outcomes and Pharmacokinetics in Chinese Patients With Metastatic Colorectal Cancer

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 583 (actual)
• Sponsor: The Affiliated Hospital of the Chinese Academy of Military Medical Sciences · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to investigate the influence of dose selection of CPT-11 on toxicity, response and pharmacokinetics according to UGT1A1 genotype in colorectal cancer patients.

Detailed description

Genetic polymorphisms of UGTs result in reduced enzyme activity and increased toxicity. UGT1A1\*28 and UGT1A1\*6 are reported to increase CPT-11-related toxicity in Asian patients. Moreover, the area under concentration curve (AUC) ratio of SN-38G to SN-38 is decreased in Asian patients having UGT1A1 \*28 or UGT1A1\*6. This implicated that the current standard dose of CPT-11 would be overdosing for homozygous UGT1A1\*28/\*28, \*6/\*6 or \*28/\*6 patients. The study is designed to investigate the role of prospectively dose reduction of CPT-11 in toxicity, tumor response and pharmacokinetics for homozygous UGT1A1 patients, and compare these parameters to standard dose of CPT-11 for wild-type, heterozygous or homozygous UGT1A1 patients.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Irinotecan Injection [Camptosar]	CPT-11 will be administered according to UGT1A1 genotypes. Patients with UGT1A1 \*1/\*1 or heterozygous UGT1A1\*1/\*28 or \*1/\*6 will receive standard dose of CPT-11. Patients with homozygous UGT1A1\*28/\*28, \*6/\*6 or \*28/\*6, will be randomized in a 1:1 ratio to receive standard dose of CPT-11 or 50% reduced dose of CPT-11.
DRUG	5-fluorouracil	The 5-FU dosage will remain the standard.
DRUG	Leucovorin	The LV dosage will remain the standard.

Timeline

• Start date: 2012-03-08
• Primary completion: 2015-11-23
• Completion: 2016-04-27
• First posted: 2012-02-01
• Last updated: 2017-03-30

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study