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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
ClinicalTrials.gov Identifier:
NCT01523431
First received: January 19, 2012
Last updated: December 26, 2013
Last verified: December 2013

January 19, 2012
December 26, 2013
March 2012
December 2013   (final data collection date for primary outcome 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 ] [ Designated as safety issue: Yes ]
Incidence and grade of neutropenia and diarrhea are record in the whole treatment duration according to NCI-CTC AE 3.0 version
Same as current
Complete list of historical versions of study NCT01523431 on ClinicalTrials.gov Archive Site
  • Association between UGT1A1 polymorphism and irinotecan pharmacokinetics [ Time Frame: First 3 days from the treatment beginning ] [ Designated as safety issue: No ]
    Determine human plasma concentrations of irinotecan and its metabolites, SN-38, SN-38G, using high-performance liquid chromatography with fluorescence detector (HPLC-FLD)
  • Progression-free survival [ Time Frame: an expected average of 6 months ] [ Designated as safety issue: No ]
    PFS is defined as the length of time from randomise to disease progression of or to death from any cause other than progression.
  • Response rate [ Time Frame: every 6 weeks,an expected average of 6 months ] [ Designated as safety issue: No ]
    According to RECIST criteria
Same as current
Not Provided
Not Provided
 
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 Pharmacokinetics and Clinical Outcome in Chinese Patients With Metastatic Colorectal Cancer

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Colorectal Cancer
Drug: CPT-11
CPT-11 will be administered according to UGT1A1 genotypes, while the doses of infusional 5-FU/LV will remain the standard dose.
Other Name: irinotecan
  • Active Comparator: homozygous UGT1A1*1
    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.
    Intervention: Drug: CPT-11
  • Active Comparator: UGT1A1*1/*28 or UGT1A1*1/*6
    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.
    Intervention: Drug: CPT-11
  • Experimental: UGT1A1*28/*28 or*6/ *6 or *28/*6
    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.
    Intervention: Drug: CPT-11
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
500
September 2014
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
China
 
NCT01523431
MCRC-307PLAH-XJM
No
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Not Provided
Principal Investigator: Xu jianming, MD The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP