UMIN-CTR Clinical Trial

Basic information
Public title	A feasibility study of EdoXaban for the Cancer-Associated asymptomatic Venous thromboEmbolism in Japanese gastrointestinal cancer patients receiving chemotherapy. (ExCAVE study)
Acronym	ExCAVE study
Scientific Title	A feasibility study of EdoXaban for the Cancer-Associated asymptomatic Venous thromboEmbolism in Japanese gastrointestinal cancer patients receiving chemotherapy. (ExCAVE study)
Scientific Title:Acronym	ExCAVE study
Region	Japan

Condition
Condition	Gastrointestinal cancer: colorectal cancer, non-colorectal cancer (gastroesophageal, pancreatic, and biliary cancer)
Classification by specialty	Gastroenterology Hepato-biliary-pancreatic medicine Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the safety of edoxaban for treatment of incidental asymptomatic VTE in gastrointestinal cancer patients receiving chemotherapy.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Incidence of major bleeding and clinically relevant non-major bleeding during 3 months after enrollment. Major bleeding events included those that were fatal; occurred in a critical area or organ (eg, intracranial); or caused a fall in hemoglobin of 2 g/dL or more or led to a transfusion of 2 or more units of whole blood or red cells. All non-major bleeding events that required any medical or surgical intervention were classified as clinically relevant non-major bleeding.
Key secondary outcomes	Diminution rate of VTE during 3 months after enrollment. Time to diminution of VTE Total amounts of edoxaban Incidence of newly symptomatic/asymptomatic VTE Subgroup analysis: Site of TE, dose of edoxaban, site of primary cancer, renal function, body weight, age

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	The edoxaban (Lixiana) is orally administered as a once-daily dosing within three days before enrollment. The once-daily starting dose is 60mg.For patients with one or more factors that increase the risk of bleeding, such as renal impairment (CrCl 15-50mL.min), low body weight (under 60 kg), concomitant use of P-gp inhibitors (e.g. cyclosporine, dronedarone, ketoconazole, erythromycin), the dose is reduced by half.
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	90 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Histologically confirmed adenocarcinoma in colorectal or non-colorectal cancers, including esophageal, gastric, pancreatic, and biliary cancer. 2) Newly diagnosed, incidental, asymptomatic deep-vein thrombosis involving the popliteal, femoral, or iliac veins or asymptomatic pulmonary embolism during GIC chemotherapy. 3) Identified with no VTE cases at the time of induction of chemotherapy by pre-screening test. 4) Patients 20 years of age or older and 90 years or younger are eligible at the time of informed consent. 5) Written informed consent to participate as a subject in this clinical study. 6) The following bone marrow, liver, and kidney function parameters measured within 14 days prior to enrollment: i) Neutrophil count: over 1500/uL ii) Platelet count: over 75000/uL iii) Hemoglobin: over 7.0 g/dL iv) Total bilirubin: under 1.5 mg/dL v) AST,ALT levels: under 2xULN vi) serum creatinine levels: < 1.5 mg/dL 7) ECOG PS of 0 to 2 8) Life expectancy of at least 90 days after enrollment
Key exclusion criteria	1) Symptomatic VTE or PE at the time of diagnosed. 2) Patients who had received thrombectomy,IVC filter catheterization, and any other anticoagulant therapy. 3) In investigator's decision that the case need to be treated as acute VTE. 4) No prior screening tests for the presence of venous thromboembolic disease was performed, such as computer tomography and/or venous ultrasonography. 5) Planned treatment with a vitamin K antagonist. 6) Patients who had received treatment for more than 72 hours with therapeutic doses of heparin, low-molecular-weight heparin, more than twice dose of a vitamin K antagonist. 7) Active bleeding 8) Having several high risk factor of VTE within 3 months. 9) Known protein C or S deficiency, antithrombin deficiency, hyperhomocysteinemia, and anti-phospholipid antibody syndrome. 10) Severe hypertension which have poorly controlled despite the medication. 11) continued to receive treatment with NSAIDs except an aspirin at a dose of more than four days a week. 12) continued to receive treatment with aspirin at a dose of more than 100mg daily or dual antiplatelet therapy. 13) contined to receive treatment with dronedarone. 14) Renal dysfunction (CCR under 30mL/min) 15) Accumulation of pleural, ascitic, or pericardial fluid requiring drainage 16) Any other active illness such as severe cardiac disease (e.g. myocardial infarction, angina pectoris, arrhythmia, or cardiac failure). Any of the following events within the 24 weeks prior to enrollment. 17) Serious hypersensitivity to any drug. 18) Current severe liver disease. 19) Active infection and/or inflammatory diseases. 20) Severe cardiac failure (over NYHA II) 21) Ineligible for participating in this study according to the investigator.
Target sample size	100

Research contact person
Name of lead principal investigator	1st name Yoshito Middle name Last name Komatsu
Organization	Hokkaido University Hospital
Division name	Cancer Center
Zip code	060-8648
Address	Kita-15-Jo, Nishi-5-chome, Kita-ku, Sapporo, Hokkaido, Japan
TEL	011-716-1161
Email	ykomatsu@ac.cyberhome.ne.jp

Public contact
Name of contact person	1st name Michio Middle name Last name Nakamura
Organization	Sapporo City General Hospital
Division name	Dept. of Gastroenterology
Zip code	060-8604
Address	1-1, Kita 11 jo Nishi 13 Chome, Chuo-ku, Sapporo, JAPAN
TEL	011-726-2211
Homepage URL
Email	michio.nakamura@icloud.com

Sponsor
Institute	HGCSG(Hokkaido Gastrointestinal Cancer Study Group)
Institute
Department

Funding Source
Organization	Daiichi-Sankyo, 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	Hokkaido University Certified Review Board
Address	Kita14 Nishi5, Kita-ku, Sapporo, Hokkaido
Tel	011-706-7934
Email	recjimu@huhp.hokudai.ac.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	jRCTs011180030
Org. issuing International ID_1	Japan Registry of Clinical Trials
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	特定非営利活動法人　北海道消化器癌化学療法研究会（HGCSG）

Other administrative information
Date of disclosure of the study information	2017 Year 08 Month 22 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
Recruitment status	Main results already published
Date of protocol fixation	2017 Year 06 Month 23 Day
Date of IRB	2017 Year 08 Month 23 Day
Anticipated trial start date	2017 Year 10 Month 01 Day
Last follow-up date	2019 Year 12 Month 31 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 08 Month 03 Day
Last modified on	2021 Year 11 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027726