UMIN-CTR Clinical Trial

Basic information
Public title	Evaluation of Oral Care in preventing Oral Mucositis in Estrogen Receptor Positive Metastatic Breast Cancer Patients Treated with Everolimus: Randomized Controlled Phase III Trial
Acronym	Oral Care-BC
Scientific Title	Evaluation of Oral Care in preventing Oral Mucositis in Estrogen Receptor Positive Metastatic Breast Cancer Patients Treated with Everolimus: Randomized Controlled Phase III Trial
Scientific Title:Acronym	Oral Care-BC
Region	Japan

Condition
Condition	Metastatic or recurrent breast cancer
Classification by specialty	Breast surgery Dental medicine
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To examine whether the occurrence of stomatitis can be reduced by dental oral management in patients by the comparison of dental oral management by instruction from dental oral surgeons and an observation group in a randomized, controlled study in female patients using everolimus for estrogen receptor-positive, hormone therapy-resistant or -refractory breast cancer.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase III

Assessment
Primary outcomes	Incidence of stomatitis in over Grade 1 after everolimus treatment (evaluated by a cancer treatment doctor)
Key secondary outcomes	Each incidence of stomatitis in over Grade 2, or over Grade 3, (evaluated by a cancer treatment doctor) Each incidence of stomatitis in over Grade 1, over Grade 2 or over Grade 3 (evaluated by a cancer treatment doctor) Time to first occurrence of stomatitis Duration of each Grade of stomatitis Each ratio of patients in suspension, or dose-reduction of everolimus treatment due to stomatitis Oral Assessment Guide (Revised)1 Health-related quality of life(HRQOL) Time to treatment failure (TTF)

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	No treatment
Stratification
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Prevention
Type of intervention	Medicine
Interventions/Control_1	Everolimus treatment
Interventions/Control_2	dental oral management
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	Female
Key inclusion criteria	1)Female patient with a histological diagnosis of breast cancer. 2)Inoperable metastatic breast cancer, or metastatic progression/recurrent breast cancer after surgical operation. 3) Patient confirmed histologically to have ER-positive breast cancer. 4)Postmenopause 5)Any of the below conditions indicating resistance to aromatase inhibitor ; a)Recurrent breast cancer ; Recurrence during adjuvant therapy of aromatase inhibitor, or after the therapy within 12 months or below. b)Advanced breast cancer ; Progression during the treatment using aromatase inhibitor, or after the treatment within a month or below. 6)Any number of chemotherapy (anti-neoplastic drugs) are allowed since diagnosis of metastatic or recurrent breast cancer. 7) Aged >=20 years 8)ECOG Performance Status: 0 or 1 9)Previous treatment (including adjuvant therapy) satisfies all of below. a)Hormone therapy: At least 7 days have elapsed from last day of hormone therapy before the beginning of this protocol therapy. b)Radiation therapy: At least 14 days have elapsed from last day of irradiation before the beginning of this protocol therapy. 10)Organ function (within 4 weeks before enrollment) a)ANC >=1,500/mm3, or WBC >=3,000/mm3 b)Platelet count >=100,000/mm3 c)Total bilirubin <=2.5 times of ULN d)AST(GOT) and ALT(GPT) <=2.5 times of ULN e)Serum creatinine <=1.5 times of ULN (Upper limit of normal) 11)Others, Cardiac function 12)Written Informed Consent
Key exclusion criteria	1)Toothless jaw 2)Occurrence of stomatitis within 1 month prior to randomization 3)Chemotherapy used within 1 month prior to randomization 4)Exemestane monotherapy used just before the randomization (this is not met, if this therapy has not been used for over 3 months before randomization) 5) Previous mTOR inhibitor treatment (everolimus, etc.) 6)Interstitial pneumonia or pulmonary fibrosis. 7)Treatment with drugs, which are known to have a strong inhibitory or inductive effect on the cytochrome P450 (CYP) 3A isozymes, within 5 days prior to randomization. The dugs are shown below ; rifabutin, rifampicin, clarithromycin, ketoconazole, voriconazole, ritonavir, telithromycin 8)HBs antigen positive, and HBc antibody and/or HBs antibody positive. 9)HCV infection, or a history of HCV infection. 10)History of hypersensitivity to a protocol treatment drug or a vehicle in the drug preparation. 11)Multiple active cancers (homochronous multiple cancers, or heterochronous multiple cancers with a disease-free period of less than 5 years prior to randomization). 12)HER2 overexpression (Her2/neu, Erb B2), and requirement of trastuzumab (herceptin) treatment. In other words, patients that satisfy any of the below conditions will be excluded. At either the primary lesion or the metastatic lesion: a)Strongly Positive (3+) by HER2 immunohistochemical (IHC) test. b)Positive (+) by FISH (fluorescence in situ hybridization). 13)Brain metastasis that requires intracranial hypertension or emergency irradiation of the brain. 14)Extensive liver metastasis, or lymphangitic lung metastasis with accompanying dyspnea. 15)Pleural effusion, ascites, or pericardial effusion that requires emergency treatment. 16)Active infectious disease. 17)Uncontrolled diabetes mellitus or diabetes currently receiving insulin therapy. 18)Study participation is difficult due to mental illness or psychiatric symptoms. 19)Unable to participate the trial by an investigator's judgment
Target sample size	200

Research contact person
Name of lead principal investigator	1st name Middle name Last name Naoki Niikura (1), Yoshihide Ohta (2)
Organization	(1)(2)Tokai University School of Medicine
Division name	(1)Departments of Breast and Endocrine Surgery, (2)Departments of Dentistry and Oral and Maxillofacial Surgery
Zip code
Address	143 Shimokasuya, Isehara, Kanagawa, 259-1193 Japan
TEL	0463-93-1121
Email	niikura@is.icc.u-tokai.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Akira Yamao
Organization	Public Health Research Foundation
Division name	Comprehensive Support Project for Oncology Research
Zip code
Address	1-1-7, Nishiwaseda, Shinjyuku-ku Tokyo, 169-0051 JAPAN
TEL	03-5287-2636
Homepage URL	http://www.csp.or.jp/
Email	support@csp.or.jp

Sponsor
Institute	Oral Care-BC executive committee
Institute
Department

Funding Source
Organization	Novartis International AG
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
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Address
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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	愛知県がんセンター中央病院、朝日大学歯学部附属村上記念病院、大阪医療センター、大阪市立大学医学部附属病院、太田記念病院、神奈川県立がんセンター、川崎医科大学附属病院、がん感染症センター都立駒込病院、岐阜市民病院、京都府立医科大学附属病院、くまもと森都総合病院、群馬県立がんセンター、神戸市立医療センター中央市民病院、国立がん研究センター東病院、さいたま赤十字病院、札幌医科大学附属病院、四国がんセンター、静岡県立総合病院、渋川医療センター・石田歯科医院、千葉大学医学部附属病院、手稲渓仁会病院、東海大学医学部付属病院、長崎原爆病院、長崎大学病院、名古屋市立大学病院、浜松医療センター、浜松オンコロジーセンター・あがた歯科、兵庫医科大学病院、広島市立広島市民病院、北海道がんセンター、りんくう総合医療センター

Other administrative information
Date of disclosure of the study information	2015 Year 01 Month 05 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	2014 Year 12 Month 17 Day
Date of IRB	2014 Year 07 Month 22 Day
Anticipated trial start date	2015 Year 03 Month 26 Day
Last follow-up date	2018 Year 03 Month 31 Day
Date of closure to data entry	2018 Year 10 Month 16 Day
Date trial data considered complete	2018 Year 10 Month 16 Day
Date analysis concluded

Other
Other related information

Management information
Registered date	2015 Year 01 Month 05 Day
Last modified on	2019 Year 10 Month 18 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018713