UMIN-CTR Clinical Trial

Public title

Non-resectable colorectal liver metastases of KRAS mutant type treated with oxaliplatin, fluorouracil and l-leucovorin plus bevacizumab induction toward liver R0 resection trial

Acronym

NEXTO-mt

Scientific Title

Non-resectable colorectal liver metastases of KRAS mutant type treated with oxaliplatin, fluorouracil and l-leucovorin plus bevacizumab induction toward liver R0 resection trial

Scientific Title:Acronym

NEXTO-mt

Region

Japan

Condition

Non-resectable colorectal liver metastases (KRAS mutant type)

Classification by specialty

Gastroenterology	Hematology and clinical oncology	Gastrointestinal surgery
Hepato-biliary-pancreatic surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate the efficacy and safety of surgery and modified FOLFOX6+bevacizumab as induction chemotherapy for metastatic colorectal cancer with non-resectable KRAS mutant liver metastases

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

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, Histopathologic assessment

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Maneuver

Interventions/Control_1

Induction chemotherapy (mFOLFOX6 + bevacizumab) 4-12 courses plus additional mFOLFOX6 1 course, followed by surgery, followed by post-operative chemotherapy (mFOLFOX6 + bevacizumab) 0-7 courses.
*(Inducion plus post-operative adjuvant chemotherapy: up to a total of 12 courses)

.mFOLFOX6
Bevacizumab 2.5mg/kg/week
L-OHP 85mg/m2
l-LV 200mg/m2
5-FU 400mg/m2 (bolus)
5-FU 2400mg/m2 (infusion)
every 2weeks

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

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 the 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)
C) Initial or recurrent liver metastases are permitted if liver metastases are metachronous
(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 KRAS mutant 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 bilirubib level: <=1.5mg/dL
- serum creatinine level: <=1.5mg/dL
- AST: <=100IU/L
- ALT: <=100IU/L
- albumin: >=3.0g/dL
- Urinary protein: 1+<=
- PT(INR): <1.5
(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) A past history of hemoptysis
(6) Patients who has not recovered from previous cancer treatment to less than Grade 1 toxicity
(7) Fully recovered from surgical treatment within 4 weeks before registration
(8) Received widespread radiation therapy within 6 weeks before registration
(9) Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval
(10) Severe infectious disease
(11) Pleural effusion, ascites fluid and the pericardial fluid needing treatment
(12) Watery diarrhea (watery colostomy output without trouble during patient's daily living is allowed)
(13) Chronic systemic treatment of corticosteroid
(14) Bleeding tendency, coagulation disorder, abnormality of coagulation factor, or administered anticoagulant
(15) HBsAg positive, HCV-Ab positive or HIV positive
(16) Women who are unwilling to avoid pregnancy. Women who are pregnant or breastfeeding. Women with a positive pregnancy test
(17) Psychological disorder
(18) Considered not appropriate for surgery
(19) Patients who are judged inappropriate for the entry into the study by the investigator

Target sample size

50

Name of lead principal investigator

1st name
Middle name
Last name	Norihiro Kokudo

Organization

The University of Tokyo

Division name

Hepato-biliary-pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine

Zip code

Address

7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan

TEL

03-3815-5411

Email

kokudo-2su@h.u-tokyo.ac.jp

Name of contact person

1st name
Middle name
Last name	Kiyoshi Hasegawa, Masaru Oba

Organization

The University of Tokyo

Division name

Hepato-biliary-pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine

Zip code

Address

7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan

TEL

03-3815-5411

Homepage URL

Email

nexto2-office@umin.org

Institute

Hepato-biliary-pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine

Institute

Department

Personal name

Organization

No

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立国際医療センター国府台病院(千葉県)、東邦大学医療センター　大森病院(東京都)、関東労災病院（神奈川県）、虎の門病院（東京都）、がん研有明病院（東京都）、防衛医科大学校病院（埼玉県）、JR東京総合病院（東京都）、東京新宿メディカルセンター（東京都）、NTT東日本関東病院（東京都）、国立国際医療研究センター（東京都）、東都文京病院（東京都）、東京高輪病院（東京都）、

Date of disclosure of the study information

2012

Year

12

Month

13

Day

URL releasing protocol

Publication of results

Unpublished

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

Recruitment status

Open public recruiting

Date of protocol fixation

2012

Year

12

Month

05

Day

Date of IRB

Anticipated trial start date

2012

Year

12

Month

25

Day

Last follow-up date

2018

Year

01

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

12

Month

12

Day

Last modified on

2015

Year

12

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011192