UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A randomized, phase III trial of sequential capecitabine/5FU plus bevacizumab (Cape/5FU-Bmab) to capecitabine/5FU plus oxaliplatin plus bevacizumab (CapeOX/mFOLFOX6-Bmab) versus combination CapeOX/mFOLFOX6-Bmab in advanced colorectal cancer.
Title of the study (Brief title)	C Cubed Study (JSWOG C-4)
Region	Japan

Condition
Condition	advanced and/or recurrent colorectal cancer
Classification by specialty	Gastroenterology Gastrointestinal surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the superiority of capecitabine (or LV5FU2) + bevacizumab followed by XELOX (or FOLFOX) + bevacizumab compared to XELOX (or FOLFOX) + bevacizumab as first-line treatment in metastatic colorectal carcinoma.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase III

Assessment
Primary outcomes	Time to Failure of Strategy
Key secondary outcomes	Progression free-survival,Overall survival, Quality of Life,Overall response rate (ORR),Time to treatment-failure, Duration of disease control, Safety

Base
Study type	Interventional

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

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	XELOX(or FOLFOX)+Bevacizumab is given until disease progression.
Interventions/Control_2	Capecitabine (or LV5FU2)+Bevacizumab is given until disease progression. After progression, XELOX(or FOLFOX)+Bevacizumab is given until disease progression.
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) Histopathologically confirmed colorectal cancer 2) Advanced or recurrent colorectal cancer who are not candidate for curative resection (1)Patients with advanced colorectal cancer who had received no intervention expect surgical procedure(R0 surgery is not included). (2)Patients with recurrent colorectal cancer who have not been administered any therapy to the recurrent site. (six months after Adjuvant is not included). 3) Age of 20 years or older 4) ECOG performance status of 0-2 5) Presence of evaluable lesions as confi rmed by CT or MRI; no previous chemo therapy or radiotherapy 6) Life expectancy longer than 90 days 7) Oral administration is possible 8) Adequate organ function according to following laboratory values obtained within 14 days before enrolment (Data recorded nearest to the entry should be referred. And excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neu >=1,500/mm3 Pt >=10.0*10^4 /mm3 Hb >=8.0 g/dL T-bil <=2.0mg/dl AST and ALT <=100IU/l (Liver metastasis =< 200IU/l) sCr <=Institution standard value*1.5 Ccr >=30mL/min(Cockcroft-Gault) Proteinuria <=1+ PT- INR <3.0 9) Written informed consent after receiving explanation of planned treatments in the study
Key exclusion criteria	1) History of active double cancer within 5 years 2) History of serious drug hypersensitivity or serious drug allergy. 3) Sever renal failure, hematologic toxicities, diarrhea, infections, massive pleural effusion, peritoneal fluid 4) Sever or uncontrolled complications (diabetes mellitus, High blood pressure, diarrhea, abnormality of the electrolyte). 5) Complication of cerebrovascular disease or the symptoms within 1 year 6) Bleeding tendency, coagulopathy (PT-INR>=3.0 within 1week prior to entry) 7) Thrombosis, thromboembolism, or receiving anticoagulant drugs (except aspirin under 325 mg/day) 8) Unhealed wound, or major surgical procedure within 28 days prior to enrollment in the study 9) Invasive assessment within 7 days prior to enrollment in the study excluding regular blood sampling, drip infusion, endoscopic examination, and central port 10) Aortic aneurysm and aortic dissection 11) Uncontrollable peptic ulcer 12) Concurrent or history of gastrointestinal perforation (within 1 year before enrollment) 13) Untreated traumatic bone fracture 14) Uncontrolled hypertension 15) Peripheral neuropathy >=Grade1 16) Patients who are pregnant, lactating, with child-bearing potential or have no intention to use contraceptive measures. 17) History of adverse events related to DPD deficiency 18) Mental disorders or central nervous system disease which could hinder treatments of the study 19) Patients who is judged by the investigator to be inappropriate for study participation for any reason. *Data recorded nearest to the entry should be referred.
Target sample size	304

Research contact person
Name of lead principal investigator	Yoshiyuki Yamaguchi
Organization	Kawasaki Medical School
Division name	Department of Clinical Oncology
Address	577 matsushima Kurashiki city Okayama Japan
TEL	086-462-1111
Email	shogo@med.kawasaki-m.ac.jp

Public contact
Name of contact person	Morihiro Fujita
Organization	NPO Japan Southwest Oncology Research Support Organization
Division name	Study Secretariat
Address	14-19-602 Nobori-cho Naka-ku Hiroshima Japan
TEL	082-222-1350
Homepage URL
Email	office@jswog.org

Sponsor
Institute	NPO Japan Southwest Oncology Research Support Organization
Institute
Department

Funding Source
Organization	CHUGAI 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)

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	2014 Year 10 Month 14 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 08 Month 28 Day
Anticipated trial start date	2014 Year 12 Month 01 Day
Last follow-up date	2018 Year 03 Month 31 Day
Date of closure to data entry	2018 Year 11 Month 06 Day
Date trial data considered complete	2019 Year 02 Month 22 Day
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2014 Year 10 Month 10 Day
Last modified on	2019 Year 02 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017596