Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients

Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients With Advanced Colorectal or Gastric Cancer Treated With FOLFIRI Regimen

The purpose of this study is to investigate the association between UGT1A1 polymorphisms and neutropenia and diarrhea in Korean patients with advanced colorectal or gastric cancer treated with FOLFIRI regimen.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer; Stage IV Colorectal Cancer
• Intervention / Treatment: Drug: Irinotecan, 5FU, leucovorin

• Study Type: Interventional
• Enrollment (Anticipated): 1500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Goyang, Korea, Republic of
    • National Cancer Center
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of
      • Samsung Medical Center
  • Hwasun-gun
    • Chŏnam, Hwasun-gun, Korea, Republic of
      • Hwasun Hospital
  • Nowon-Gu
    • Seoul, Nowon-Gu, Korea, Republic of
      • Korea Cancer Center Hospital
  • Songpa-Gu
    • Seoul, Songpa-Gu, Korea, Republic of, 05505
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Subjects should meet all of the following criteria to participate in the trial.

• Histologically confirmed colorectal or gastric cancer patients who are chemonaive or failed to 1st line chemotherapy
• Subjects who are expected to receive toxicity test at least once after FOLFIRI treatment.
• Aged 18 years or older.
• ECOG performance status of ≤ 2.
• Anticipated life expectancy of ≥ 3 months.

• Clinically acceptable function of bone marrow, kidney and liver function as below.

  1. ANC ≥ 1500/mm3 and platelet count ≥ 100,000/mm3
  2. 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)
  3. Serum creatinine ≤ 1.5 mg/dL or CLcr > 60 ml/min
• Subjects whose written informed consent can be obtained prior to their participation in the trial.

Exclusion Criteria: Subjects who meet any of the following criteria should not be included in the trial.

• Pregnant or breast feeding women
• Serious concurrent complication, severe active infection.
• Subjects with chronic diarrhea, paralytic ileums, pulmonary fibrosis or pneumonia interstitialis
• Subjects with epilepsia or severe psychiatric disorders.
• Subjects who are regarded to be unsuitable for this trial by the investigator.
• Subjects who are participating in other clinical trials
• Subjects who have received prior chemotherapy including irinotecan.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FOLFIRI; Patients with colorectal cancer or gastric cancer will be treated with FOLFIRI(Irinotecan, 5FU, leucovorin) regimen upto 12 cycles. (Single arm study)	Drug: Irinotecan, 5FU, leucovorin; FOLFIRI regimen every 2 weeks [irinotecan 150mg/m2 or 180mg/m2, leucovorin 20(200)mg/m2, 5FU 400 mg/m2 (bolus) or 2400 mg/m2 (46hour infusion)]; Other Names: CAMPTO (CAMPOSAR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between UGT1A1 polymorphism and grade 3/4 neutropenia after 1st cycle of FOLFIRI treatment	During the first cycle of treatment	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between UGT1A1 polymorphism and grade 3/4 neutropenia in all treatment duration	During all treatment period(during 12 cycle, each 2 weeks)	24 weeks
Association between grade 3/4 diarrhea and UGT1A1 polymorphism	During the first cycle of treatment	2 weeks
Progression-free survival	The time from registration to objective tumor progression or death	6 months (average)

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Study Director: YongSang Hong, Professor, Asan Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): June 1, 2014
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: January 4, 2011
• First Submitted That Met QC Criteria: January 6, 2011
• First Posted (Estimate): January 7, 2011

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 27, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Gastric cancer; Irinotecan; Neutropenia; UGT1A1; Colorecatal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Leucovorin; Irinotecan
• Other Study ID Numbers: CPT_08_001