UMIN-CTR Clinical Trial

Basic information
Public title	Phase II study investigating efficacy and safety of TFTD plus bevacizumab by RAS mutation status in patients with unresectable advanced or recurrent colorectal cancer refractory or intolerant to standard chemotherapy
Acronym	PhaseII study investigating efficacy and safety of TFTD plus bevacizumab by RAS mutation status in patients with unresectable advanced or recurrent colorectal cancer refractory or intolerant to standard chemotherapy (JFMC51-1702-C7)
Scientific Title	Phase II study investigating efficacy and safety of TFTD plus bevacizumab by RAS mutation status in patients with unresectable advanced or recurrent colorectal cancer refractory or intolerant to standard chemotherapy
Scientific Title:Acronym	PhaseII study investigating efficacy and safety of TFTD plus bevacizumab by RAS mutation status in patients with unresectable advanced or recurrent colorectal cancer refractory or intolerant to standard chemotherapy (JFMC51-1702-C7)
Region	Japan

Condition
Condition	Colorectal cancer
Classification by specialty	Gastroenterology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To investigate the efficacy and safety of TFTD plus bevacizumab by RAS mutation status in patients with unresectable advanced or recurrent colorectal cancer refractory or intolerant to standard chemotherapy
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Disease control rate (DCR) by RAS mutation status
Key secondary outcomes	DCR in full analysis set Progression-free survival Overall survival Objective response rate Safety Efficacy and safety by the BRAF mutation status (exploratory outcome)

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	No need to know

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	TFTD: 35 mg/m. given orally twice daily on days 1-5 and 8-12 in a 28-day cycle Bevacizumab: 5 mg/kg, administered by intravenous infusion for 30 min every 2 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	1.Histologically confirmed advanced or recurrent colorectal adenocarcinoma (exclude appendix and anal cancer) 2.Unresectable colorectal cancer confirmed by imaging 3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4.Confirmed RAS mutation status 5.Treatment history of one or more regimens of standard chemotherapy (1) Refractory or intolerant to fluoro pyrimidine, irinotecan, oxaliplatin, angiogenesis inhibitor (bevacizumab, ramucirumab, or aflibercept), and anti-EGFR antibody (cetuximab or panitumumab) for wild-type RAS (2) Exclude history of intolerance to bevacizumab (3)Include history of adjuvant chemotherapy if a tumor had relapsed within 6 months after the last administration 6 No treatment history of regorafenib and TFTD 7.Measurable lesions based on the Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) within the 21 days before enrolment 8.Adequate bone marrow,hepatic,and renal functions 9.Written informed consent
Key exclusion criteria	1.History of intolerance to bevacizumab 2.Thromboembolic events within the 6 months before enrolment 3.Active bleeding 4.Severe heart disease within the 6 months before enrolment 5.Cerebrovascular events 6.Active infections 7.Ascites, pleural effusion, or pericardial effusion requiring treatment 8.Gastrointestinal obstruction, renal failure, or liver failure 9.Uncontrolled diabetes mellitus 10.Uncontrolled hypertension 11.Positive for Hepatitis B surface antigen (HbsAg+) or Hepatitis C antibody (HCV Ab+) 12.Other active cancer 13.Symptomatic brain metastases 14.Requiring immunosuppressive treatment due to an autoimmune disorder or history of organ transplantation 15.Treatment history; (1)Major surgery (i.e., thoracotomy or laparotomy) within the 4 weeks before enrollment (2)Chemotherapy within the 2 weeks before enrollment (3)Extensive exposure of radiation within the 4 weeks before enrollment 16.Unresolved adverse events of grade 2 or higher (classified with the National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from previous treatment 17.Unhealed wound or traumatic fracture 18.tendency of haemorrhage and undergoing treatment with an antithrombotic drug (including a daily dose of 325 mg or more of oral aspirin) 19.Females who are in pregnancy, breastfeeding, with a positive pregnancy test or unwilling to use adequate contraception or males of reproductive potential 20.Clinically significant mental or psychological disorder 21.Patients whose participation in the trial was judged to be inappropriate by the investigator
Target sample size	100

Research contact person
Name of lead principal investigator	1st name 1)TAKAO 2)KENTARO 3)EIJI Middle name Last name 1)TAKAHASHI 2)YAMAZAKI 3)OKI
Organization	1)Gifu University, Graduate School of Medicine 2)Shizuoka Cancer Center 3)Graduate School of Surgery and Science Kyushu University
Division name	1)Department of Surgical Oncology 2)Division of Gastrointestinal Oncology 3)Department of Surgery and Science
Zip code	1)501-1194 2)411-8777 3)812-8582
Address	1) 1-1 Yanagido, Gifu city, GIFU,501-1194, Japan 2)1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, SHIZUOKA, 411-8777, Japan 3)3-1-1 Maidashi, Higashi-ku, Fukuoka City, FUKUOKA, 812-8585, Japan
TEL	03-5627-7594
Email	jfmc51@jfmc.or.jp

Public contact
Name of contact person	1st name TAKAO Middle name Last name TAKAHASHI
Organization	Gifu University, Graduate School of Medicine
Division name	Department of Surgical Oncology
Zip code	501-1194
Address	1-1 Yanagido, Gifu city, GIFU,501-1194, Japan
TEL	03-5627-7594
Homepage URL	http://www.jfmc.or.jp/
Email	jfmc51@jfmc.or.jp

Sponsor
Institute	Japanese Foundation for Multidisciplinary Treatment of Cancer
Institute
Department

Funding Source
Organization	TAIHO PHARMACEUTICAL CO.,LTD
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	National Cancer Center Hospital East
Address	6-5-1 Kashiwanoha, Kashiwa city, Chiba
Tel	04-7133-1111
Email	ncche-irb@east.ncc.go.jp

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	2018 Year 01 Month 09 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications	https://doi.org/10.1016/j.esmoop.2021.100093
Number of participants that the trial has enrolled	102
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	2017 Year 09 Month 05 Day
Date of IRB	2018 Year 12 Month 06 Day
Anticipated trial start date	2019 Year 01 Month 09 Day
Last follow-up date	2020 Year 09 Month 10 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 11 Month 22 Day
Last modified on	2021 Year 07 Month 12 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034327