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

Colonic Neoplasms Clinical Trial

Official title:

Comparison of Standard and High Dose Irinotecan Based on UGT1A1 Genotype, 5-fluorouracil, and Leucovorin (FOLFIRI) for First-line Treatment of Locally Advanced Colon Cancer: a Prospective Phase II Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01826396
• Other study ID #: CCIHeilongjiang-001
• Status: Recruiting
• Phase: Phase 2
• First received: April 4, 2013
• Last updated: April 4, 2013
• Start date: April 2013
• Est. completion date: December 2014

Study information

• Verified date: April 2013
• Source: Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences
• Contact: Zheng Jiang, doctor
• Phone: +81 451 86297661
• Email: dr.jiangzheng[@]gmail.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age 18 to 70 years old, male or female;

2. ECOG performance status of 0-1;

3. Confirm the diagnosis pathologically locally advanced colon adenocarcinoma;

4. TNM stage is T4NxM0;

5. According to RECIST 1.1 version of the standard, at least measurable lesions without local treatment; spiral CT or magnetic resonance imaging (MRI), thickness = 5 mm lesion diameter = 10mm, such as lymph short diameter required = 15mm;

6. Each organ function was normal (in the case of no ongoing support therapy, enrolled within one week of the laboratory examination results); 1)absolute neutrophil count (ANC) = 1.5x109 / L, platelet count = 80x109 / L, hemoglobin 9g/dL; 2)serum total bilirubin = 1.5 times the upper limit of normal; 3)ALT and AST = 2.5 times the upper limit of normal without liver metastases, liver metastases = upper limit of normal in ALT and AST 5 times; 4)= upper limit of normal, serum creatinine or creatinine clearance = 50ml/min.

7. This study has been fully understood and voluntarily signed the informed consent form;

8. Expected to survive for more than three months.

Exclusion Criteria:

1. Pregnancy or lactating women or fertility patients are reluctant to take contraceptive measures;

2. who are allergic to irinotecan, fluorouracil;

3. can not be controlled in the central nervous system (CNS) metastasis;

4. Suffering from any other malignancy (fully cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer excluded) within five years. 5.Clinical uncontrolled active infection such as acute pneumonia, with active hepatitis B;

6.with severe systemic disease, including, but not limited to, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, acute myocardial infarction, unstable angina, congestive heart failure, severe arrhythmia, thrombosis occurred within 6 months or embolic events (including transient ischemic attack); 7.Acute or subacute intestinal obstruction; 8.Symptoms of ascites, pleural effusion, and pericardial effusion, can not draining or symptomatic treatment control; 9.according to the NCI CTC AE 3.0 standard 2 or more than 2 toxicity or researchers believe that patients with any clinical or laboratory abnormalities are unfit to participate in the clinical research; 10.Also accept other systemic anti-cancer therapy (local radiotherapy of bone metastases from this restriction) to accept other trial medication in the 4 weeks before the start of the study; 11.History of serious psychological or psychiatric disorders, drug addiction or alcohol dependent persons; 12.estimated that the lack of compliance of patients enrolled in the clinical study.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colonic Neoplasms

Intervention

Drug:
• Irinotecan
Comparison of standard and high dose irinotecan

Locations

Country	Name	City	State
China	Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences	Harbin	Heilongjiang

Sponsors (1)

Lead Sponsor	Collaborator
Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	adverse reactions		one year	Yes
Primary	R0 resection rate		one year	No
Secondary	disease free survival		one year	No