UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase II trial of regorafenib in patients with imatinib resistrant gastrointestinal stromal tumor
Title of the study (Brief title)	RESET for GIST
Region	Japan

Condition
Condition	Gastrointestinal stromal tumor (GIST)
Classification by specialty	Gastroenterology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the efficacy and safety of regorafenib in patients with imatinib resistant GIST
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Progression free survival rate at 24weeks.
Key secondary outcomes	Progression free survival:PFS Objective response rate:RR Disease control rate:DCR Clinical effective rate(Objective response or SD persists more than 22weeks.) Adverse event:AE

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
Interventions/Control_1	Regorafenib(160mg)is administered orally once daily
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 who have been fully informed about the study and have given written consent themselves 2) Patients aged 20 years or older at the time of consent 3) Patients with histologically confirmed metastatic and/or unresectable GIST. 4) Imatinib was discontinued due to disease progression or an adverse event. 5) No prior treatment with Regorafenib or Sunitinib. 6) ECOG Performance Status 0-1 7) Patients able to take oral medications. 8) With measurable lesion according to RECIST ver.1.1.. 9) Adequate organ function a. Hemoglobin >=8.0 g/dL b. Absolute neutrophil count >=1,000 /mm3 c. Platelet count >=100,000 /mm3 d. Total bilirubin <=1.8 mg/dL e. AST and ALT <=100 IU/L f. Serum creatinine <=1.5mg/dL 10) Women of childbearing potential must have a negative pregnancy test within 7days prior to enrollment.Patients who do have intention that uses effective contraception method until 6 months after administering investigational drug. 11) Patient is willing or able to comply with the protocol.
Key exclusion criteria	1) Serious coexisting illness as follows. a. Active double cancer(s) b. CNS metastasis c. Uncontrollable infectious disease d. Uncontrollable pleural effusion, ascites, or cardiac effusion within 2weeks prior to enrollment e. Ileus, renal failure, hepatic failure or cerebrovascular disorder within 6months prior to enrollment f. Interstitial pneumonia or pulmonary fibrosis apparent on CT g. Uncontrolled diabetes mellitus h. Uncontrolled hypertension i.Cardiac infarction, serious or unstable angina or New York Heart Association Class III or IV within 12 months prior to enrollment j Needs antiarrhythmic treatment k. Gastrointestinal bleeding within 4 weeks. l. Positive HBs antigen or HIV antibody m. Need immunosuppressive therapy n. Uncontrolled mental disease or the psychotic manifestation o. Pheochromocytoma 2) Receive the treatment as follows. a.Major surgery therapy within 4 weeks prior to enrollment. b.Chemotherapy (except Imatinib) within 3 weeks prior to enrollment. c. Imatinib within 1 week prior to enrollment. d.Wide field radiotherapy 4 weeks prior to enrollment e.Other investigational drugs within 4 weeks prior to enrollment. 3) Unrecovered AEs related to prior treatment are Grade >= 2 according to CTCAE. 4) Blood transfusion or G-CSF within 14 days prior to enrollment. 5) Gastrointestinal malabsorption 6) Serious renal failure or proteinuria >= 2+ within 7days prior to enrollment 7) Thromboembolic event within 6 months prior to enrollment 8) Untrecovered wound or traumatic fracture 9) Need anticoaglation 10) Women during pregnancy or lactation , 11) Known hypersensitivity to Regorafinib or Regorafinib's excipient 12) Tendency to hemorrhages or Grade >= 3 bleeding within 4 weeks. 13) Patient is judged by the investigator to be inappropriate for study participation for any reason.
Target sample size	38

Research contact person
Name of lead principal investigator	Toshihiko Doi
Organization	National Cancer Center East Hospital
Division name	Experimental Therapeutics
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba
TEL	04-7133-1111
Email	tdoi@east.ncc.go.jp

Public contact
Name of contact person	Yoichi Naito
Organization	National Cancer Center East Hospital
Division name	Experimental Therapeutics
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba
TEL	04-7133-1111
Homepage URL
Email	ynaito@east.ncc.go.jp

Sponsor
Institute	National Cancer Center East Hospital
Institute
Department

Funding Source
Organization	Bayer Yakuhin 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	国立がん研究センター中央病院(東京都） 国立がん研究センター東病院(千葉県） 北海道大学病院(北海道） 大阪大学医学部附属病院(大阪府） 兵庫県立がんセンター(兵庫県） 九州大学病院（福岡県）

Other administrative information
Date of disclosure of the study information	2015 Year 01 Month 13 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2014 Year 11 Month 04 Day
Anticipated trial start date	2015 Year 01 Month 30 Day
Last follow-up date	2018 Year 12 Month 05 Day
Date of closure to data entry	2019 Year 02 Month 28 Day
Date trial data considered complete
Date analysis concluded

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

Management information
Registered date	2015 Year 01 Month 05 Day
Last modified on	2019 Year 01 Month 07 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018716