Standard and High Dose Irinotecan Based on UGT1A1 Genotype for First-line Treatment of Locally Advanced Colon Cancer

Sponsor
Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences
Study ID
NCT01826396
Phase
PHASE2
Status
Unknown

Conditions

  • Colonic Neoplasms

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Irinotecan — DRUG
    Comparison of standard and high dose irinotecan

Study Details

In the current treatment of colon cancer, the definition of locally advanced colon cancer (LACC) is controversial, and the clinical trial evidence which support treatment for LACC is not clear. Irinotecan (CPT-11) combined with fluoropyrimidine (5FU, capecitabine) is main chemotherapy regimen for patients with advanced colorectal cancer. Whether this regimen also could be effectively applied for patients with locally advanced colon cancer? It is worthy of clinicians to conduct research. In recent studies, the literature indicated that the the uridine diphosphate glucuronide transfer enzyme (UGT1A1) is an important metabolic enzymes associated with drug metabolism of CPT-11. The gene polymorphism of UGT1A1 is related to delayed diarrhea and neutropenia caused by irinotecan. Irinotecan dose-exploration study found that the maximum tolerated dose for irinotecan in patients with UGT1A1\*28 homozygous variant genotypes was significantly lower compared with the wild genotype. The studies based on Asian patients suggested that the gene variant of UGT1A1\*6 also have similar impacts. At present, the studies of irinotecan dose adjustment based on the UGT1A1 gene polymorphisms has not yet come to the consistency of conclusions. The frequency of UGT1A1 gene polymorphisms between different races is significant different, irinotecan dose exploratory study based on Chinese patients has not been carried out. This study focus on prospectively adverse reactions, optimal efficacy and R0 resection rate of the patients with LACC who treated by dose-adjusted irinotecan based on the genotypes of UGT1A1.

Key Dates

Start date
Apr 30, 2013
Status verified
Apr 2013
Primary completion
Apr 30, 2014
Completion
Dec 31, 2014

Study Design

Enrollment
100 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: high dose irinotecan
    high dose irinotecan based on UGT1A1 genotype, 5-fluorouracil, and leucovorin (FOLFIRI) for first-line treatment of locally advanced colon cancer

Primary Outcome Measure

R0 resection rate [ Time Frame: one year ]

Central Contacts

Related Studies