UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	The project to investigate mTOR inhibitor-induced immune modulation in subjects with renal cell cancer.
Title of the study (Brief title)	Japanese m-TOR Immune Modulation Trial(J-TORIM)
Region	Japan

Condition
Condition	advanced renal cell carcinoma
Classification by specialty	Urology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To investigate temsirolimus-induced immune modulation relevant to clinical efficacy or adverse events in subjects with RCC.
Basic objectives2	Others
Basic objectives -Others	To investigate temsirolimus-induced immune modulation relevant to tumor response (Objective Response Rate, ORR), progression free survival(PFS) and overall survival(OS). To investigate temsirolimus-induced immune modulation relevant to adverse events on the lungs(ie. Interstitial Lung Disease, ILD) or other than ILD.
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Changes on the immune-relevant parameter by temsirolimus-induced immune modulation.
Key secondary outcomes

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
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	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1.Unresectable or metastatic renal carcinoma patients who were diagnosed from the results of cytological or pathological studies. 2.Patients who had more than one measurable lesions according on CT or MR imaging to the Response Evaluation Criteria in Soild Tumors (RECISTv.1.1). 3.Patients with aged 18 and over. 4.Patients with performance status 0-1 (ECOG). 5.Patients who does not observe a stromal shade in a lung by thorax CT. 6.Patients with an appropriate major organ function (liver, kidney, and myeloid). 7.Patients who meets all the following standards. FBS<=1.5 x ULN Total cholesterol<=400mg/dL Trigliceride<=5.0 x ULN 8.Patients with expected survival for 3 months or longer. 9.Patients with written informed consent from the patient (In the case of underage, from both the patient himself and legally acceptable representative ). 7.Patients who meets all the following standardses. FBS<=1.5 x ULN Total cholesterol<=400mg/dL Trigliceride<=5.0 x ULN 8.Patients with expected survival for 3 months or longer. 9.Patients with written informed consent from the patient.
Key exclusion criteria	1.Patients with known hypersensitivity to temsirolimus or its metabolites (including sirolimus). 2.Female patients of childbearing potential (including male patients of planning to childbear ) and becoming pregnant. 3.Patients treated with m-TOR inhibitor or performed prior immunotherapy within 6 months. 4.Patients treated with systemic steroidal therapy or immunosuppressive drug. 5.Patients with brain metastasis. 6.Patients with active double cancers. 7.Patients with active infectious disease. 8.In addition, patients whom a doctor in judge unsuitable as a candidate patients of an examination.
Target sample size	30

Research contact person
Name of lead principal investigator	Masatoshi Eto
Organization	Faculty of Life Sciences, Kumamoto University
Division name	Department of Urology
Address	Honjo 1-1-1 Kumamoto City, Kumamoto, Japan
TEL	096-344-2111
Email	info2@cres-kyushu.or.jp

Public contact
Name of contact person	Yoshihiro Wada
Organization	Faculty of Life Sciences, Kumamoto University
Division name	Honjo 1-1-1 Kumamoto City, Kumamoto, Japan
Address	Honjo 1-1-1 Kumamoto City, Kumamoto, Japan
TEL	096-344-2111
Homepage URL
Email	yoshiwad@kumamoto-u.ac.jp

Sponsor
Institute	Departmentof Urology, Faculty of Life Sciences, Kumamoto University
Institute
Department

Funding Source
Organization	Departmentof Urology, Faculty of Life Sciences, Kumamoto University
Organization
Division
Category of Funding Organization	Other
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	熊本大学大学院生命科学研究部(熊本県） 札幌医科大学病院(北海道） 弘前大学大学院医学研究科（青森県） 広島市立安佐市民病院(広島県） 浜松医科大学医学部（静岡県） 岩手医科大学医学部(岩手県） 九州大学大学院医学研究院(福岡県） 東北大学大学院医学系研究科（宮城県） 奈良県立医科大学(奈良県） 徳島大学大学院(徳島県） 防衛医科大学校(埼玉県） 宮崎大学医学部(宮崎県） 大阪大学大学院医学研究科(大阪府） 四国がんセンター（愛媛県） 山形大学医学部(山形県） 山口大学大学院医学系研究科(山口県） 北海道大学大学院医学研究科(北海道） 京都大学大学院医学研究科(京都府）

Other administrative information
Date of disclosure of the study information	2013 Year 01 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 10 Month 26 Day
Anticipated trial start date	2013 Year 01 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information	1.Samples: peripheral blood mononuclear cells taken from the patients. Serial sampling is required as follows; 1)Just before starting temsirolimus. In cases after TKI (sorafenib, sunitinib, axitinib), wash-out time of at least 2 weeks is necessary. 2)Early phase of treatment with temsirolimus (Three - five weeks after the starting of treatment with temsirolimus). 3)(option) Just after the occurrence of abnormal findings on chest imaging (In the case of necessity of the treatment to ILD, before the treatment). 4)(option) At the resolution phase of ILD (In the case of lack of improvement within 2 weeks, 2 weeks after the onset of ILD). 2.Item for measures: 1)Proliferation activity of T cells, assessed by tritium thymidine uptake stimulated by ConA. 2)The expression profiles of B7-H1 on CD3+, CD4+T cells and CD3+, CD8+T cells. 3)The expression profiles of PD-1 on CD3+, CD4+T cells and CD3+, CD8+T cells. 4)The ratio of Foxp3+CD4+CD25+regulatory T cells in the total CD4+CD25+T cells. *2) to 4) are assessed by flow cytometry 5) Production of IFN-gamma and IL-6 from LPS-stimulated PBMCs, assessed by ELISA.

Management information
Registered date	2012 Year 12 Month 28 Day
Last modified on	2017 Year 04 Month 30 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011331