UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Non-resectable colorectal liver metastases treated with cetuximab induction toward liver R0 resection trial
Title of the study (Brief title)	NEXTO
Region	Japan

Condition
Condition	Non-resectable colorectal liver metastases
Classification by specialty	Gastroenterology Hematology and clinical oncology Gastrointestinal surgery Hepato-biliary-pancreatic surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy and the safety of surgery and mFOLFOX6+cetuximab as induction chemotherapy for metastatic colorectal cancer with non-resectable liver metastases.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Liver metastases R0 resection rate
Key secondary outcomes	Safety (AE), All R0 resection rate, Liver metastases R0+R1 resection rate, Central review of resectability, Tumor reduction rate, Response rate, Disease free survival, Progression Free Survival, Overall survival

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 Maneuver
Interventions/Control_1	Induction chemotherapy (mFOLFOX6 + cetuximab) 4-12 cycles followed by surgery, followed by post-operative adjuvant chemotherapy (mFOLFOX6 + cetuximab) 0-8 cycles. (induction plus post-operative chemotherapy: up to a total of 12 cycles) cetuximab (loading dose 400mg/m2, 250 mg/m2/week), mFOLFOX6 (L-OHP 85 mg/m2/biweekly, Levofolinate 200 mg/m2/biweekly, 5-FU/bolus 400 mg/m2/biweekly, 5-FU/continuous 2,400 mg/m2/biweekly)
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	(1) Patients with histologically proven colorectal cancer (2) No prior local therapy for liver metastases and presence of measurable lesion in liver (RECIST Ver.1.1) (3) A) Non-resectable or more than 5 liver limited metastases B) Non-resectable or more than 5 liver metastases with resectable extrahepatic metastases (except for peritoneal dissemination) (4) Resectable primary lesion and extrahepatic metastases except as noted below; A) Primary lesion : Patients with imminent risk of obstruction or significant bleeding B) Extrahepatic metastases : Patients with peritoneal dissemination (5) Metastatic colorectal cancer with EGFR expression and KRAS wild type (6) Age over 20 years (7) ECOG Performance Status(PS) 0-1 (8) No prior chemotherapy for colorectal cancer (9) Patients have enough organ function for study treatment - neutrophil count >=1,500/mm3 - platelet >=100,000/mm3 - serum bilirubin level <=1.5mg/dL - serum creatinine level <=1.2mg/dL - AST <=100IU/L - ALT <=100IU/L - albumin >=3.0g/dL (10) Life expectancy of more than 3 months (11) Written informed consent
Key exclusion criteria	(1) Prior local therapy for liver metastases (2) Severe comorbidity (3) A past history of drug allergy (needs continuation therapy) (4) A past history of Interstitial lung disease (5) Patients who has not recovered from previous cancer treatment to less than Grade 1 toxicity (6) Fully recovered from surgical treatment within 4 weeks before registration (7) Received widespread radiation therapy within 6 weeks before registration (8) Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval (9) Severe infectious disease (10) Pleural effusion, ascites fluid and the pericardial fluid needing treatment (11) Watery diarrhea (watery colostomy output without trouble during patient's daily living is allowed) (12) Chronic systemic treatment of corticosteroid (13) Bleeding tendency, coagulation disorder, abnormality of coagulation factor, or administered anticoagulant (14) HBsAg positive, HCV-Ab positive or HIV positive (15) Women who are unwilling to avoid pregnancy. Women who are pregnant or breastfeeding. Women with a positive pregnancy test (16) Psychological disorder (17) Considered not appropriate for surgery (18) Patients who are judged inappropriate for the entry into the study by the investigator
Target sample size	50

Research contact person
Name of lead principal investigator	Norihiro Kokudo
Organization	The University of Tokyo
Division name	Hepato-biliary-pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine
Address	7-3-1 Hongo, Bunkyo-ku, Tokyo
TEL	03-3815-6511
Email	KOKUDO-2SU@h.u-tokyo.ac.jp

Public contact
Name of contact person	Kiyoshi Hasegawa, Masaru Oba
Organization	The University of Tokyo
Division name	Hepato-biliary-pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine
Address	7-3-1 Hongo, Bunkyo-ku, Tokyo
TEL	03-3815-5411
Homepage URL
Email	nexto-office@umin.org

Sponsor
Institute	Hepato-biliary-pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
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)

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	都立墨東病院(東京都）、防衛医科大学校病院(埼玉県)、関東労災病院外科（神奈川県)、日立総合病院(茨城県)、虎の門病院(東京都)、がん研有明病院(東京都)、独立行政法人 地域医療機能推進機構群馬中央病院(群馬県)、国立国際医療研究センター国府台病院(東京都)、茨城県立中央病院(茨城県)、東邦大学医療センター　大森病院(東京都)、国立国際医療研究センター病院(東京都)、独立行政法人地域医療機能推進機構東京高輪病院(東京都)、総合病院 国保旭中央病院(千葉県)、河北総合病院(東京都)、日本大学医学部附属板橋病院(東京都)、帝京大学医学部付属病院(東京都)、NTT東日本関東病院(東京都)、公立昭和病院(東京都)、独立行政法人 地域医療機能推進機構東京山手メディカルセンター(東京都)、埼玉県立がんセンター(東京都)

Other administrative information
Date of disclosure of the study information	2012 Year 05 Month 11 Day

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2012 Year 04 Month 04 Day
Anticipated trial start date	2012 Year 05 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Partially published
URL releasing results
Results
Other related information

Management information
Registered date	2012 Year 05 Month 10 Day
Last modified on	2016 Year 12 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009328