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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences
Sponsor:
Information provided by (Responsible Party):
Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01826396
First received: April 4, 2013
Last updated: NA
Last verified: April 2013
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Colonic Neoplasms
Drug: Irinotecan
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences:

Primary Outcome Measures:
  • R0 resection rate [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • disease free survival [ Time Frame: one year ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • adverse reactions [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: April 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Irinotecan
Comparison of standard and high dose irinotecan
Other Name: CPT-11, CAMPTO

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01826396

Contacts
Contact: Zheng Jiang, doctor +81 451 86297661 dr.jiangzheng@gmail.com

Locations
China, Heilongjiang
Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences Recruiting
Harbin, Heilongjiang, China, 150001
Contact: Zheng Jiang, doctpr    +81 451 86297661    dr.jiangzheng@gmail.com   
Sponsors and Collaborators
Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences
Investigators
Study Chair: Xishan Wang, doctor Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences
  More Information

No publications provided

Responsible Party: Colorectal Cancer Institute of the Heilongjiang Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT01826396     History of Changes
Other Study ID Numbers: CCIHeilongjiang-001
Study First Received: April 4, 2013
Last Updated: April 4, 2013
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Colonic Neoplasms
Colonic Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014