UMIN-CTR Clinical Trial

Basic information
Public title	Pharmacogenomic study on colorectal cancer chemotherapy - modified FOLFOX6- (Oxaliplatin with infusional 5-FU/l-Leucovorin) and FOLFIRI (irinotecan with infusional 5-FU/l-Leucovorin)-based regimen-
Acronym	Pharmacogenomic study on colorectal cancer chemotherapy
Scientific Title	Pharmacogenomic study on colorectal cancer chemotherapy - modified FOLFOX6- (Oxaliplatin with infusional 5-FU/l-Leucovorin) and FOLFIRI (irinotecan with infusional 5-FU/l-Leucovorin)-based regimen-
Scientific Title:Acronym	Pharmacogenomic study on colorectal cancer chemotherapy
Region	Japan

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

Objectives
Narrative objectives1	To assess the efficacy and safety of modified FOLFOX6 and FOLFIRI with or without Bevacizmab for Stage IV unresectable colorectal cancer: Multicentric phase II randomized study. Predictive formulaes for CPT11 and mFOLFOX6 that have been developed for tailored-therapy will be validated for their possibility of application. Novel biomarker candidates will also be explored for these therapies.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Response rate (RECISTv1.1)
Key secondary outcomes	Evaluation of efficacy and safety. (1) Overall response duration, Complete response duration, Stable duration (2)Progression free survival (3)Time to treatment failure (4)Survival: Overall survival, OS, Median survival Time, 1-year survival, 2-year survival (5) Toxicity profiles, frequency, grade, timing Feasibility of novel and known biomarkers (1)Feasibility of novel biomarkers for prediction of response (2) Feasiblity of known biomarkers for prediction of efficacy or adverse effects (3) Establishment of new predictive markers,

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	4
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	mFOLFOX6 (-BEV): On Day1, iv infusion of 85 mg/m2 of l-OHP and 175 mg/m2 of L-LV for 2hrs, followed by bolus infusion of 400 mg/m2 5-FU. Then, continuous infusion of 2400 mg/m2 5-FU for 46 hrs. 1 course, 2 weeks. Continue the courses till the discontinuance criteria.
Interventions/Control_2	mFOLFOX6 (+BEV): The first treatment after the surgery is subject to the mFOLFOX6 (-BEV) regimen. From the 2nd cycle, first infusion of 5 mg/kg BEV. Then follow the mFOLFOX6 (-BEV) regimen. 1 course, 2 weeks. Continue the courses till the discontinuance criteria.
Interventions/Control_3	mFOLFIRI(-BEV): On Day1, iv infusion of 150 mg/m2 of CPT-11 and 175 mg/m2 of L-LV for 2 hrs, followed by bolus infusion of 400 mg/m2 5-FU. Then, continuous infusion of 2400 mg/m2 5-FU for 46 hrs. 1 course, 2 weeks. Continue the courses till the discontinuance criteria.
Interventions/Control_4	mFOLFIRI (+BEV): The first treatment after the surgery is subject to the FOLFIRI (-BEV) regimen. From the 2nd cycle, first infusion of 5 mg/kg BEV. Then follow the FOLFIRI (-BEV) regimen. 1 course, 2 weeks. Continue the courses till the discontinuance criteria.
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	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Histologically confirmed colorectal cancer. 2) Stage IV unresectable case. 3) The patient must have measurable disease (RECIST) 4) Patient must have appropriate organ function (bone marrow, liver, kidney, cardiac, etc.) and the laboratory value within 7 days before the protocol treatment must be WBC 4,000/mm3 or more ANC 2,000/mm3 or more Platelet 100,000/mm3 or more Hemoglobin 9.0g/dl or more AST, ALT x2 institutional ULN or less (For the liver metastatic cases, x3 institutional ULN or less) Serum Total Bilirubin 1.5 mg/dL or less Serum Creatinine 1.5 mg/dL or less Creatinine clearance 60 ml/min or more BUN 25mg/dl or less ECG Normal 5) ECOG Performance Status 0-2 6) Any therapy should not have been given for the current disease. 7) Protocol treatment must be started within 6 weeks after surgery. 8) Collected tissue sample must be enough for genomic analysis. 9) Life expectancy must be 12 weeks or more at the time of registration. 10) Age 20 years or older 11) Written informed consent must be obtained for the study including blood or tissue sampling.
Key exclusion criteria	1) Patients with obvious infectious disease. 2) Patients with watery diarrhea. 3) Patients with intestinal paralysis, obstruction, or subobstruction of bowel (At the time of registration) 4) Patients with interstitial pneumonia or pulmonary fibrosis 5) Patients with considerable cancerous body cavity fluid. 6) Patients with severe paresthesia of functional disorder or dysesthesia 7) Patients with peripheral (sensory or motor) neuropathy Grade 2 or greater (CTCAEv4.0). 8) Patients with treatment-required ischemic heart disease or cardiac disease such as arrhythmia (left ventricular hypertrophy associated with hypertension, mild left ventricular over-loading, or mild right bundle branch block etc. are acceptable for registration) 9) Patients with history of myocardial infarction within 6 months 10) Patients with liver cirrhosis 11) Patients with active bleeding at bowel with necessity for frequent transfusion 12) Patients with clinically serious psycho-neurological disease required for continuation therapy using psychotropic drug 13) Patients with uncontrollable diabetes 14) Patients with active double cancer 15) Patients with history of severe hypersensitivitie for other drugs 16) Patients required for continuous administration of phenytoin 17) Patients with obvious intraperitoneal inflammation 18) Patients with uncured surgical wound of serious operation 19) Patients with congenital hemorrhagic diathesis 20) Patients with administration of anticoagulant such as warfarin potassium 21) Patients with history of thromboembolism 22) Patients who are pregnant or breast feeding or possibility of pregnancy 23) Patients with severe comorbidity who are difficult for continuation of the protocol treatment
Target sample size	210

Research contact person
Name of lead principal investigator	1st name Middle name Last name Masahiko Nishiyama
Organization	Saitama Medical University
Division name	Frontier Medical Development Center
Zip code
Address	1397-1 Yamane, Hidaka, Saitama 350-1298, Japan
TEL	042-984-4668
Email

Public contact
Name of contact person	1st name Middle name Last name Masahiko Nishiyama
Organization	Saitama Medical University
Division name	Frontier Medical Development Center
Zip code
Address	1397-1 Yamane, Hidaka, Saitama 350-1298, Japan
TEL	042-984-4668
Homepage URL
Email	yamacho@saitama-med.ac.jp

Sponsor
Institute	Personalized Medicine Study Group for Cancer
Institute
Department

Funding Source
Organization	None
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	YES
Study ID_1	DOFMET Protocol #5
Org. issuing International ID_1	Development Organization for Frontier Medical Therapeutics
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

九州大学大学院医学研究院・消化器総合外科学 （福岡県）、 熊本大学大学院生命科学研究部・消化器外科学　（熊本県）、 鹿児島大学大学院医歯学総合研究科・腫瘍制御学・消化器外科学　（鹿児島県）、 ICSG (Individualized Chemotherapy Study Group) 　関西労災病院・外科　（兵庫県） 　市立堺病院・外科　（大阪府） 　市立吹田市民病院・外科・消化器内科　（大阪府） 　大阪府立成人病センター・消化器外科，臨床腫瘍科　（大阪府） 　兵庫医科大学・下部消化器外科　（兵庫県） 　　医療法人薫風会 佐野病院　（兵庫県）、 岐阜大学大学院医学研究科・腫瘍外科学　（岐阜県）、 北里大学医学部・外科学　（神奈川県）、 帝京大学ちば総合医療センター・外科　（千葉県）、 群馬大学大学院医学研究科病態総合外科学　（群馬県）、 埼玉医科大学総合医療センター・消化管・一般外科　（埼玉県）、 岩手医科大学・外科学　（岩手県）、 埼玉医科大学先端医療開発センター　（埼玉県）

Other administrative information
Date of disclosure of the study information	2011 Year 12 Month 19 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
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	2011 Year 09 Month 29 Day
Date of IRB	2011 Year 11 Month 25 Day
Anticipated trial start date	2011 Year 12 Month 01 Day
Last follow-up date	2015 Year 12 Month 01 Day
Date of closure to data entry	2016 Year 01 Month 30 Day
Date trial data considered complete	2016 Year 01 Month 30 Day
Date analysis concluded	2016 Year 01 Month 30 Day

Other
Other related information

Management information
Registered date	2011 Year 12 Month 19 Day
Last modified on	2019 Year 06 Month 25 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000008162