UMIN-CTR Clinical Trial

Basic information
Public title	Pharmacogenomic Study for Individual Response to CPT-11 in Colorectal Cancer Patients (Step 2)
Acronym	Pharmacogenomic Study of CPT-11 in Colorectal Cancer Patients (Step 2)
Scientific Title	Pharmacogenomic Study for Individual Response to CPT-11 in Colorectal Cancer Patients (Step 2)
Scientific Title:Acronym	Pharmacogenomic Study of CPT-11 in Colorectal Cancer Patients (Step 2)
Region	Japan

Condition
Condition	Stage IV colorectal cancer after palliative operation
Classification by specialty	Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the efficacy and safety of weekly 100 mg/m2 CPT-11 administration as the first-line adjuvant chemotherapy for Stage IV colorectal cancer patients, and identify the potent biomarkers
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase II

Assessment
Primary outcomes	1)Tumor response rate 2)Genotype-phenotype association (CYP3A4,CES1,2, UGT1A1, ABCG2, ABCB1, and ABCC1,2 vs toxicity), mutation -phenotype association (TOP1A, ABCG2 vs tumor response), and expression-phenotype association (TOP1A, ABCG2 vs tumor response)
Key secondary outcomes	1)Adverse events, 2)Progression free-survival (PFS) 3)Overall survival (OS) 4)Genotype-phenotype association (CYP3A4,CES1,2, UGT1A1, ABCG2, ABCB1, and ABCC1,2 vs PK parameter) Gene expression-phenotype association (TOP1A, ABCG2 vs PK parameter) 5)Possible biomarkers other than the above 9 genes 6)Microsatellite instability (MSI)- phenotyppe association (BAT26, D2S136, D3S1067, TP53, and D18S51 vs tumor response)

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
Interventions/Control_1	Intravenous adminstration of CPT-11 100 mg/m2 on Days 1, 8, and 15, every 4 weeks
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	20 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key inclusion criteria	(1)With pathologically proven colorectal cancer (2)With Stage IV colorectal cancer after palliative operation (3)With at least one measurable lesion (RECIST) (4)With adequate bone marrow, cardiac, respiratory, hepatic, and renal functions. Defined as: white blood cell count 4000-12,000 mm3, neutrophil count>=2000 mm3, hemoglobin>=9.0 g/dl, platelet>=100,000 mm3, AST and ALT within two times the upper limit of normal for the institution, serum bilirubin level<=1.5 mg/dl, BUN<=25 mg/dl, serum creatinine level<=1.5 mg/dl, creatinine clearance>=50 ml/min., C-reactive protein<=1.0 mg/dl, normal ECG (5)ECOG performance status<=2 (6)No prior therapy other than the palliative operation (7)Palliative operation was completed>=21 days prior to entry (8)Life expectancy estimated>=12 weeks (9)Age 20-75 years (10)With collected tissue samples for pharmacogenomic analysis (11)With written informed consent
Key exclusion criteria	(1)Other serious accompanied diseases (2)Symptomatic infectious disease (3)Watery diarrhea (4)Ileus, Obstructive bowel disease (5)Interstitial pneumonia, pulmonary fibrosis (6)Symptomatic ascites or pleural effusion (7)Symptomatic jaundice (8)Ischemic heart disease or arrhythmia required medical care (9)Myocardiac infarction occurred within 6 month, (10)Liver cirrhosis (11)Hemorrhage/bleeding>=grade 3 (NCI-CTC) (12)Symptomatic psychological disease (13)Uncontrollable diabetes (14)Serious surgery-related complication (15)Active secondary cancer (16)A past history of drug allergy (17)Pregnancy or breast feeding (18)Active hepatitis or syphilis
Target sample size	50

Research contact person
Name of lead principal investigator	1st name Middle name Last name Masahiko Nishiyama
Organization	Research Institute for Radiation Biology and Medicine, Hiroshima University
Division name	Department of Translational Cancer Research
Zip code
Address	1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
TEL	082-257-5839
Email

Public contact
Name of contact person	1st name Middle name Last name Masahiko Nishiyama
Organization	Research Institute for Radiation Biology and Medicine, Hiroshima University
Division name	Department of Translational Cancer Research
Zip code
Address	1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
TEL	082-257-5839
Homepage URL	http://www.hictdo.or.jp/tiken.html
Email	yamacho@hiroshima-u.ac.jp

Sponsor
Institute	Hiroshima Cancer Therapy Development Organization (HiCTDO)
Institute
Department

Funding Source
Organization	Hiroshima Cancer Therapy Development Organization (HiCTDO)
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Osaka Med. Ctr. Cancer and Cardiovasc. Dis., Sakai City Hosp., Osaka Seamen's Insurance Hosp., Kobe Univ., Hokkaido Univ., Suita Municipal Hosp., Aomori Municipal Hosp., Hiroshima Univ.
Name of secondary funder(s)	None

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	YES
Study ID_1	HiCTDO protocol #3
Org. issuing International ID_1	Hiroshima Cancer Therapy Development Organization (HiCTDO)
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2005 Year 10 Month 01 Day

Related information
URL releasing protocol	http://www.hictdo.or.jp/tiken.html
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results	Paper is being prepared (Sep.1/2008)
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 04 Month 05 Day
Date of IRB
Anticipated trial start date	2004 Year 04 Month 01 Day
Last follow-up date	2007 Year 12 Month 01 Day
Date of closure to data entry	2007 Year 12 Month 01 Day
Date trial data considered complete	2007 Year 12 Month 01 Day
Date analysis concluded	2008 Year 06 Month 01 Day

Other
Other related information	Interim results have been published. (ASCO2006 Abst.#2060; ESMO2006 Abst.# 841P)

Management information
Registered date	2005 Year 09 Month 01 Day
Last modified on	2008 Year 09 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000150

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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