UMIN-CTR Clinical Trial

Basic information
Public title	Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-refractory patients with EGFR-positive advanced and/or metastatic colorectal cancer, evaluation of the safety and efficacy based on KRAS mutation status (T-CORE0801)
Acronym	Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-resisitant advanced and/or metastatic colorectal cancer with KRAS mutation analysis (T-CORE0801)
Scientific Title	Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-refractory patients with EGFR-positive advanced and/or metastatic colorectal cancer, evaluation of the safety and efficacy based on KRAS mutation status (T-CORE0801)
Scientific Title:Acronym	Phase II trial of cetuximab plus irinotecan for FOLFOX and FOLFIRI-resisitant advanced and/or metastatic colorectal cancer with KRAS mutation analysis (T-CORE0801)
Region	Japan

Condition
Condition	3rd line or later therapy for unresectable advanced and/or recurrent colorectal cancer
Classification by specialty	Gastroenterology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	We confirm safety and efficacy of cetuximab plus irinotecan as a 3rd line or later therapy in patients with EGFR positive unresectable advanced and/or recurrenct colorectal cancer. We also examine KRAS mutation as a prospective analysis and compare the safety and efficacy of cetuximab plus irinotecan between KRAS wild-type and mutant group. As an accompanied study, we further examine mutations in BRAF, PIK3CA and PTEN, microsatellite instability, and two SNPs in Fcgamma receptor genes (FcgammaRIIa-H131R and FcgammmaRIIIa-V158F) and compare the safety and efficacy of cetuximab plus irinotecan.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	response rate
Key secondary outcomes	progression free survival (PFS), overall survival(OS) and safety

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	Diagnosis
Type of intervention	Medicine
Interventions/Control_1	cetuximab 400 mg/m2 given as 2 hours infusion for the first time, 250mg/m2 as 1 hour infusion for the second time or later. Irinotecan 100mg/m2 repeated every week followed by one week rest or Irinotecan 150mg/m2 repeated every two 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	Not applicable
Gender	Male and Female
Key inclusion criteria	The criteria for eligibility were histologically proven EGFR positive colorectal cancer of; an age of 20 or older; with an unresectable primary tumor or with one or more unresectable metatatic tumor(s); more than two privious treatment by FOLFOX or FOLFIRI regimen; with performance status (ECOG) 0, 1 or 2; the following interval from previous treatments (4 weeks from radiations, 2weeks from a operation with some organ resection, 2 weeks from chemotherapy, 4 weeks from other clinical trial), measurable lesions based on the RECIST; and adequate organ function (a neutrophil count of 1500 or more per cubic millimeter ; a platelet count of at least 100,000 per cubic millimeter; hemoglobin levels of more than 8.0 g per deciliter ;aspartate aminotransferase and alanine aminotransferase levels of 100 or less international unit per litter; a total bilirubin level of no more than 2.0 mg per deciliter; and a serum creatinine level of no more than 1.5 mg per deciliter; expected more than 2 months prognosis; with a written informed consent for this study
Key exclusion criteria	The exclusion criteria were symptomatic metastatic brain tumor, uncontrolled massive pleural or abdominal effusion, previous meningitis carcinomatosis, uncontrolled epilepsy, critical mental disturbance, central nervous system disorder, uncontrolled diabtes mellitus, uncontrolled hypertension, active infection treated with antibiotics, antifungal or antiviral drugs, bleeding tendency, symptomatic coagulation abnormality, acute pneumonia, interstitial pneumonitis or pulmonary fibrosis, chronic disease required the treatment with steroid or immune-suppressing drug, diarrhea; with complication of paralytic intestine, bowel obstraction (ileus), previous history of herpersensitivity (Grade 3 or severe) against monoclonal antibody drug, previous history of herpersensitivity against irinotecan, pevious therapy with inhibitor of EGF signal transduction or inhibitor of EGFR, treated with Atazanavir Sulfate, active double cancer within 5 years, Grade 3 or severe neural disturbance, Grade III or IV by NYHA classification or sever cardiac disease within 6 months.
Target sample size	40

Research contact person
Name of lead principal investigator	1st name Middle name Last name Hideki Shimodaira
Organization	Institute of Development, Aging and Cancer, Tohoku University
Division name	Department of Clinical Oncology
Zip code
Address	4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
TEL	022-7171-8547
Email	hshimoda@idac.tohoku.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Shunsuke Kato
Organization	NPO T-CORE (Tohoku Clinical Oncology Research and Education Society)
Division name	Office
Zip code
Address	4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
TEL	022-717-8599
Homepage URL	http://www.T-CORE.JP
Email	t-core-admin@umin.ac.jp

Sponsor
Institute	NPO T-CORE (Tohoku Clinical Oncology Research and Education Society)
Institute
Department

Funding Source
Organization	NPO T-CORE (Tohoku Clinical Oncology Research and Education Society)
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization	Japan

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 01 Month 31 Day

Related information
URL releasing protocol	http://www.t-core.jp
Publication of results	Published

Result
URL related to results and publications	http://www.karger.com/Article/FullText/360989
Number of participants that the trial has enrolled
Results	Results:KRAS mutations were detected in 31.7% of 41 eligible patients. The RR to cetuximab plus irinotecan therapy was found to be 17.9 and 0% in the KRAS wild-type and mutant subgroups, respectively. Conclusion: Despite the identification of a lower-than-expected RR to treatment by the KRAS wild-type subgroup, KRAS mutation status appears to be a useful predictive marker of response to cetuximab plus irinotecan therapy in Japanese mCRC patients.
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	2008 Year 12 Month 10 Day
Date of IRB
Anticipated trial start date	2009 Year 02 Month 01 Day
Last follow-up date	2012 Year 02 Month 01 Day
Date of closure to data entry	2014 Year 06 Month 01 Day
Date trial data considered complete	2014 Year 06 Month 01 Day
Date analysis concluded	2014 Year 06 Month 01 Day

Other
Other related information	As a prospective study, mutation analysis of KRAS, BRAF, PIK3CA, and PTEN genes, microsatellite instability (MSI) and two common SNPs of Fc gamma receptor genes will be examined for all enrolled patients

Management information
Registered date	2009 Year 01 Month 29 Day
Last modified on	2015 Year 07 Month 29 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001978

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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