UMIN-CTR Clinical Trial

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

Metastatic or recurrent breast cancer

Classification by specialty

Breast surgery

Dental medicine

Classification by malignancy

Malignancy

Genomic information

NO

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

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)

Study type

Interventional

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

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

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

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

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

Institute

Oral Care-BC executive committee

Institute

Department

Personal name

Organization

Novartis International AG

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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

Date of disclosure of the study information

2015

Year

01

Month

05

Day

URL releasing protocol

Publication of results

Unpublished

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

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 related information

Registered date

2015

Year

01

Month

05

Day

Last modified on

2019

Year

10

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018713