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Name:
UMIN ID:

Recruitment status Completed
Unique ID issued by UMIN UMIN000002092
Receipt No. R000002554
Scientific Title Genetic Polymorphism oriented PhaseI Study of Irinotecan and Doxifluridine for Unresectable or Recurrent Colorectal Cancer
Date of disclosure of the study information 2009/06/18
Last modified on 2010/07/21

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Basic information
Public title Genetic Polymorphism oriented PhaseI Study of Irinotecan and Doxifluridine for Unresectable or Recurrent Colorectal Cancer
Acronym Genetic Polymorphism oriented PhaseI Study of Irinotecan and Doxifluridine for metastatic Colorectal Cancer
Scientific Title Genetic Polymorphism oriented PhaseI Study of Irinotecan and Doxifluridine for Unresectable or Recurrent Colorectal Cancer
Scientific Title:Acronym Genetic Polymorphism oriented PhaseI Study of Irinotecan and Doxifluridine for metastatic Colorectal Cancer
Region
Japan

Condition
Condition colorectal cancer
Classification by specialty
Gastroenterology Gastrointestinal surgery
Classification by malignancy Malignancy
Genomic information YES

Objectives
Narrative objectives1 The aim of this study is to confirm the RD of irinotecan when combined with a fluoropyrimidine in patients with advanced colorectal cancer.
Basic objectives2 Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes Primary endpoint: MTD, DLT, recomended dose
Key secondary outcomes

Base
Study type Interventional

Study design
Basic design Single arm
Randomization Non-randomized
Randomization unit
Blinding Open -no one is blinded
Control Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms 1
Purpose of intervention Treatment
Type of intervention
Medicine Gene
Interventions/Control_1 Patients received treatment for 12 weeks. CPT-11 was administered once every two weeks in 500 ml of normal saline or dextrose via 120-min intravenous infusion on day 1, 15, 29, 43, 57 and 71. 5-DFUR was given as 200-mg capsules, two capsules were administered orally in the morning and evening after a meal on 5 consecutive days followed by a 2-day washout during the 12-week treatment period.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit
15 years-old <=
Age-upper limit
75 years-old >=
Gender Male and Female
Key inclusion criteria Patients were eligible for this study if they met the following criteria: proven unresectable or recurrent colorectal cancer; age between 20 and 75 years; no major surgery, radiotherapy or chemotherapy within 4 weeks prior to the study; Eastern Cooperative Oncology Group performance status of 0 to 2;predicted life expectancy of at least 3 months; adequate baseline organ functions, defined as a leukocyte count of at least 4,000/uL, neutrophil count of at least 2,000/uL, platelet count of at least 100,000/uL, hemoglobin of at least 9.0 g/dL, AST and ALT of 3 times or less the upper limit of the institutional reference range; total bilirubin below 1.5 mg/dL, and serum creatinine below 1.5 mg/dL.
Key exclusion criteria Patients were ineligible if they had any of the following conditions: serious infectious disease or other severe complications (e.g., pulmonary fibrosis/interstitial pneumonia, uncontrollable diabetes); watery diarrhea, paralytic ileus, or intestinal obstruction; massive pleural effusion or ascitic fluid; symptomatic brain metastases; active concurrent malignancies; pregnancy or lactation, or desire for pregnancy; a history of drug allergy; and prior treatment with CPT-11.
Target sample size 18

Research contact person
Name of lead principal investigator
1st name
Middle name
Last name Masaaki Oka
Organization Yamaguchi University Graduate School of Medicine
Division name Department of Digestive Surgery and Surgical Oncology (Surgery II)
Zip code
Address 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, JAPAN
TEL
Email

Public contact
Name of contact person
1st name
Middle name
Last name Shoichi Hazama
Organization Yamaguchi University Graduate School of Medicine
Division name Department of Digestive Surgery and Surgical Oncology (Surgery II)
Zip code
Address
TEL
Homepage URL
Email hazama@yamaguchi-u.ac.jp

Sponsor
Institute Department of Digestive Surgery and Surgical Oncology (Surgery II), and Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine
Institute
Department

Funding Source
Organization Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine
Organization
Division
Category of Funding Organization Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information
2009 Year 06 Month 18 Day

Related information
URL releasing protocol
Publication of results Published

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Although individuals carrying the UGT1A1 allele *28 have an
increased risk of severe toxicities associated with irinotecan, no
phase I study has been conducted based on the polymorphism. This
report presents the recommended doses of irinotecan for patients
with the respective genotypes. Twenty-seven patients with
advanced colorectal cancer were enrolled in this study, and the
UGT1A1*28 polymorphism was genotyped before chemotherapy.
One course of chemotherapy consisted of irinotecan infused once
every 2 weeks at 70, 100, 120, and 150 mg&#8260;m2 at dose levels 1, 2, 3,
and 4, respectively, and doxifluridine was administered orally. This
treatment continued for at least 12 weeks. The dose-limiting toxicity
was determined as grade 3 hematological and non-hematological
toxicities for the TA6 &#8260; TA6 (6 &#8260; 6) and TA6 &#8260; TA7 (6 &#8260; 7) genotypes.
The pharmacokinetics of irinotecan, SN-38, and SN-38 glucuronide,
was assessed at dose level 2. Eighteen and nine patients had the
6 &#8260; 6 and 6 &#8260; 7 genotypes, respectively. The maximum tolerated dose
(MTD) was not observed up to dose level 4 in patients with the 6 &#8260; 6
genotype. In contrast, MTD was observed at dose level 2
(100 mg&#8260;m2) in patients with the 6 &#8260; 7 genotype. Patients with the
6 &#8260; 7 genotype had a significantly higher area under the plasma
time&#8211;concentration curve 0-\ SN-38 (P = 0.022) and biliary index
(P = 0.030) than those with 6 &#8260; 6. The recommended starting doses
of biweekly irinotecan for phase II &#8260; III were 150 mg&#8260;m2 for patients
with the UGT1A1 6 &#8260; 6 genotype and 70 mg&#8260;m2 for those with the
6 &#8260; 7 genotype, respectively. The gene polymorphism should be considered
when determining the precise recommended doses to be
administered in phase I studies. (Cancer Sci 2010; 101: 722-727)
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status Completed
Date of protocol fixation
2004 Year 12 Month 20 Day
Date of IRB
Anticipated trial start date
2005 Year 01 Month 01 Day
Last follow-up date
2009 Year 12 Month 01 Day
Date of closure to data entry
2009 Year 12 Month 01 Day
Date trial data considered complete
2009 Year 12 Month 01 Day
Date analysis concluded
2009 Year 12 Month 01 Day

Other
Other related information

Management information
Registered date
2009 Year 06 Month 18 Day
Last modified on
2010 Year 07 Month 21 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002554

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name


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