UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000002092 |
|---|---|
| Receipt number | 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 20:51:03 |
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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
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
hazama@yamaguchi-u.ac.jp
Sponsor or person
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
Personal name
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
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⁄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 ⁄ TA6 (6 ⁄ 6) and TA6 ⁄ TA7 (6 ⁄ 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 ⁄ 6 and 6 ⁄ 7 genotypes, respectively. The maximum tolerated dose
(MTD) was not observed up to dose level 4 in patients with the 6 ⁄ 6
genotype. In contrast, MTD was observed at dose level 2
(100 mg⁄m2) in patients with the 6 ⁄ 7 genotype. Patients with the
6 ⁄ 7 genotype had a significantly higher area under the plasma
time–concentration curve 0-\ SN-38 (P = 0.022) and biliary index
(P = 0.030) than those with 6 ⁄ 6. The recommended starting doses
of biweekly irinotecan for phase II ⁄ III were 150 mg⁄m2 for patients
with the UGT1A1 6 ⁄ 6 genotype and 70 mg⁄m2 for those with the
6 ⁄ 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
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002554
