Overview

This trial is active, not recruiting.

Condition metastatic colorectal cancer
Treatment cpt-11
Phase phase 2
Sponsor The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Start date March 2012
End date December 2013
Trial size 500 participants
Trial identifier NCT01523431, MCRC-307PLAH-XJM

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
CPT-11(Irinotecan ) 180 mg/m2 90-minute i.v. infusion on day 1; leucovorin 400mg/m2 i.v. infusion on day 1 ; followed by 5-FU 400mg/m2 i.v. bolus on day 1, then 2400mg/m2 i.v. over 46 hours continuous infusion; repeat every two weeks.
cpt-11 irinotecan
CPT-11 will be administered according to UGT1A1 genotypes, while the doses of infusional 5-FU/LV will remain the standard dose.
(Active Comparator)
CPT-11(Irinotecan ) 180 mg/m2 90-minute i.v. infusion on day 1; leucovorin 400mg/m2 i.v. infusion on day 1 ; followed by 5-FU 400mg/m2 i.v. bolus on day 1, then 2400mg/m2 i.v. over 46 hours continuous infusion; repeat every two weeks.
cpt-11 irinotecan
CPT-11 will be administered according to UGT1A1 genotypes, while the doses of infusional 5-FU/LV will remain the standard dose.
(Experimental)
CPT-11(Irinotecan ) 90 mg/m2 90-minute i.v. infusion on day 1; leucovorin 400mg/m2 i.v. infusion on day 1 ; followed by 5-FU 400mg/m2 i.v. bolus on day 1, then 2400mg/m2 i.v. over 46 hours continuous infusion; repeat every two weeks.
cpt-11 irinotecan
CPT-11 will be administered according to UGT1A1 genotypes, while the doses of infusional 5-FU/LV will remain the standard dose.

Primary Outcomes

Measure
Association between UGT1A1 polymorphism and incidence of neutropenia and diarrhea
time frame: From first 2 weeks to the whole treatment period, an expected average of 6 months

Secondary Outcomes

Measure
Association between UGT1A1 polymorphism and irinotecan pharmacokinetics
time frame: First 3 days from the treatment beginning
Progression-free survival
time frame: an expected average of 6 months
Response rate
time frame: every 6 weeks,an expected average of 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Histologically confirmed colorectal cancer patients who received no prior chemotherapy or failed to 1st line treatments 2. At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 3. Aged 18 years or older 4. ECOG performance status of ≤ 2. 5. Anticipated life expectancy of ≥ 3 months. 6. UGT1A1 genotype tested. Categorized into Wild (UGT1A1*1/*1), Hetero (UGT1A1*1/ *28, UGT1A1*1/ *6), and Homo (UGT1A1*28/*28, UGT1A1*6/*6, UGT1A1*28/*6). 7. Adequate organ function, including bone marrow, kidney and liver. - ANC ≥ 1.5×109/L and hemoglobin ≥ 9g/dL and platelet count ≥ 100×109/L - Serum total bilirubin ≤ 1.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN, Serum ALT and AST ≤ 2.5 x ULN (Serum ALT and AST ≤ 5 x ULN, if liver metastases are present) - Serum creatinine ≤ 1.5 x ULN or CLcr > 60 ml/min 8. Written informed consent can be obtained prior to their participation in the trial. Exclusion Criteria: 1. Pregnant or breast feeding women 2. Subjects who have previously received CPT-11 treatment 3. Serious concurrent complication, severe active infection. 4. Subjects with chronic diarrhea, acute or sub acute Intestinal obstruction. 5. Subjects with uncontrolled CNS metastasis or epilepsia or severe psychiatric disorders. 6. Subjects who are regarded to be unsuitable for this trial by the investigator. 7. Subjects who are participating in other clinical trials

Additional Information

Official title Influence of Individual Dosage Selection of Irinotecan(CPT-11)Based on UGT1A1 Genotype on Pharmacokinetics and Clinical Outcome in Chinese Patients With Metastatic Colorectal Cancer
Principal investigator Xu jianming, MD
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 UGT1A1 *28 or UGT1A1 *6 genotype patients.
Trial information was received from ClinicalTrials.gov and was last updated in December 2013.
Information provided to ClinicalTrials.gov by The Affiliated Hospital of the Chinese Academy of Military Medical Sciences.