UMIN-CTR Clinical Trial

Basic information
Public title	A multicenter randomized phase II clinical trial with neo -adjuvant chemotherapy containing eribulin mesylate for triple negative primary breast cancer patients (Neo-Entrance study)
Acronym	A multicenter randomized phase II clinical trial with neo -adjuvant chemotherapy containing eribulin mesylate for triple negative primary breast cancer patients (Neo-Entrance study)
Scientific Title	A multicenter randomized phase II clinical trial with neo -adjuvant chemotherapy containing eribulin mesylate for triple negative primary breast cancer patients (Neo-Entrance study)
Scientific Title:Acronym	A multicenter randomized phase II clinical trial with neo -adjuvant chemotherapy containing eribulin mesylate for triple negative primary breast cancer patients (Neo-Entrance study)
Region	Japan

Condition
Condition	Patients with operable primary triple-negative breast cancer without prior treatment
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the efficacy and safety of neo -adjuvant chemotherapy based on eribulin mesylate for primary triple negative breast cancer
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase II

Assessment
Primary outcomes	Pathological complete response evaluated by the Central Decision Institution [CpCRypN0 (ypT0-TisypN0)]
Key secondary outcomes	- SpCR, SpCR and pN0 rate - CpCR rate - QpCR, QpCR and pN0 rate - Clinical response rate (response rate of eribulin-based, anthracycline treatments and overall response rete) - Breast-conserving surgery rate - The rate of patients with axillary lymph nodes negative at the time of surgery which have been diagnosed as node positive before NAC. - Disease-free Survival (DFS), Invasive Disease-free survival (IDFS), overall survival (OS) (DFS, IDFS, and OS will be examined in an observational study after the completion of the investigator initiated clinical trial) - Influence of an eribulin combination regimen on the effects of the second half of the regimen (anthracycline) - Influence (e.g., neutrophil counts) of blood toxicity on Days 8 and 15 in Cycle 1 of the eribulin combination regimen on the therapeutic effects of eribulin and the effects of the second half of the regimen (anthracycline) - Influence (e.g., neutrophil counts) of blood toxicity on Days 8 and 15 in Cycle 1 of the paclitaxel combination regimen on the therapeutic effects of paclitaxel and the effects of the second half of the regimen (anthracycline) - Safety in each treatment groups (adverse events, completion rates, and dose intensity)

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration
Blocking
Concealment	Central registration

Intervention
No. of arms	4
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Group A-1 Patient "with age <65 years and HRD positive" or "with BRCA mutation" 1)Combination therapy (paclitaxel + carboplatin) 4 cycles ,2)FEC or AC therapy (4 cycles) ,3) surgery Combination therapy Cycles 1-4: paclitaxel at mg/m2 once every week (day 1, day 8, day 15) + carboplatin AUC6 (once every three weeks (day 1) FEC or AC therapy Cycles 5-8: FEC therapy (5-fluorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks (No change during the FEC and AC therapies)
Interventions/Control_2	Group A-2 Patient "with age <65 years and HRD positive" or "with BRCA mutation" 1)Combination therapy (eribulin + carboplatin)(4 cycles) ,2) FEC or AC therapy (4 cycles) ,3) surgery Combination therapy Cycles 1-4: eribulin at 1.4 mg/m2 (administered once weekly for two consecutive weeks and washout in Week 3 (day 1, day 8)) + carboplatin AUC6 (once every three weeks, day 1) FEC or AC therapy Cycles 5-8: FEC therapy (5-fluorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks (No change during FEC and AC therapies)
Interventions/Control_3	Group B-1 Patient "with age <65 years and HRD negative" or "with age >=65 years(without BRCA mutation)" 1)Combination therapy (eribulin + cyclophosphamide)(6 cycles) ,2) surgery However, the antitumor effects are examined at Cycles 4 and 6 to determine whether to continue combination therapy or convert to FEC or AC therapy or surgery. Combination therapy Eribulin at 1.4 mg/m2 (administered once weekly for two consecutive weeks and washout in Week 3 (day 1,day 8)) + cyclophosphamide at 600 mg/m2 (once every three weeks, day 1) FEC or AC therapy FEC therapy (5-fluorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks) (No change during the FEC and AC therapies)
Interventions/Control_4	Group B-2 Patient "with age <65 years and HRD negative" or "with age >=65 years(without BRCA mutation)" 1)Combination therapy (eribulin + capecitabine) (6 cycles) ,2) surgery However, the antitumor effects are examined at Cycles 4 and 6 to determine whether to continue combination therapy or convert to FEC or AC therapy or surgery. Combination therapy Cycles 1-6: eribulin at 1.4 mg/m2 (administered once weekly for two consecutive weeks and washout in Week 3 (day 1,day 8)) + capecitabine at 2,000 mg/m2/day (continuously administered twice daily on Days 1-14 and washout on Days 15-21) FEC or AC therapy FEC therapy (5-fulorouracil: 500 mg/m2, epirubicin: 100 mg/m2, cyclophosphamide: 500 mg/m2) once every three weeks, or AC therapy (doxorubicin: 60 mg/m2, cyclophosphamide: 600 mg/m2) once every three weeks) (No change during the FEC and AC therapies)
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	70 years-old >=
Gender	Female
Key inclusion criteria	First key inclusion criteria (1) Age at the time of informed consent and has signed an informed consent form is between 20 and 70years (2) Primary breast cancer which is diagnosed as invasive breast cancer by needle or Vacuum-assisted breast biopsy (exclude apocrine or medullary carcinoma). (3) Resectable primary breast cancer (cT1c-cT3, cN0-cN1, and cM0)with a tumor size<=70mm in diameter. (4) Triple-negative (ER<1%, PgR<1%, and HER2-negative) is confirmed in primary lesion, Ki67 labelling index of>=10%. (5) No previous therapy for breast cancer. (6) Pt is considered as suitable indication for primary systemic therapy. (7) Pt who evaluable primary disease using contrast-enhanced MRI or PET/CT (8) Pt with evaluable primary disease using mammary ultrasonography (9) Written informed consent Secondary inclusion criteria Pt who has been determined to be eligible for the primary registration and meet all of the following conditions: (1) ECOG performance status (PS) 0-1 (2) By the pathological central review, invasive breast cancer, triple-negative breast cancer (ER <1%, PgR <1%, HER2 negative), and Ki67 labelling index of >=10% have been confirmed. (3) HRD test result is confirmed when age <65 years at consent acquisition (not required if BRCA mutations are known). (4) Clinical examination values at screening meet the criteria, with normal organ functions maintained. (5) Pt with HRD negative and the creatinine clearance >=50 mL/min when age >=65 years at consent acquisition. (6) No clinically significant arrhythmia by ECG (QTc: <=480 msec). (7) No interstitial pneumonia or lung fibrosis diagnosed by chest CT or X-ray. (8) Non-pregnancy is confirmed using a pregnancy test. (9) Pt with possibility of pregnancy must agree to take contraception. (10) HBs antigen, HBc antibody, and HBs antibody tests are all negative. In cases negative for HBs antigen and positive for HBc antibody and/or HBs antibody, HBV-DNA levels have to been below the detection limit.
Key exclusion criteria	(1) Bilateral invasive breast cancer whether metachronous,concurrent or bilateral DCIS. Contralateral DCIS after mastectomy (Bt), skin-sparing mastectomy (SSM), nipple-sparing mastectomy (NSM), or equivalent are permitted. (2) Pt with multiple cancers other than breast cancer (3) Pt with axillary lymph node dissection before pre-operative chemotherapy (4) Pt with incisional or excisional biopsies for primary lesion or axillary lymph node (5) Participation in another clinical trial within 28 days after the second registration (6) Pt with peripheral neuropathy >= NCI CTCAE v.4.03 Grade 2 (7) Pt with cardiopulmonary dysfunctions within six months before the second registration (8) Pt with myocardial infarction within 12 months before the second registration (9) Pt with severe uncontrolled systemic diseases (10) Pt who undergone major surgery or serious trauma within 28 days before the second registration, or who will have a major surgery during this trial. (11) Pt with severe infectious disease requiring intravenous administration of antibiotics, antiviral agents, or anti-fungal agents at the second registration (12) Pt with dental caries and/or oral infections requiring treatment (13) Pt with diagnosed of active liver disease or sclerosing cholangitis caused by autoimmune liver disorders (14) Pt with HIV infection (15) Lactating Pt (16)Other diseases that are considered to affect consent acquisition or protocol compliance by an investigator or sub-investigator. (17) Pt with hypersensitive to the study drug or additives and with DPD deficiency (18) Pt with difficulty of the oral ingestion, dysfunction of the upper gastrointestinal tract and malabsorption syndrome ( only in case HRD negative or age>=65 years at consent acquisition) (19) Pt determined to be ineligible by an investigator.
Target sample size	200

Research contact person
Name of lead principal investigator	1st name 1)Masakazu 2) Norikazu Middle name Last name 1)Toi 2) Masuda
Organization	1) Kyoto University Graduate School of Medicine 2) National Hospital Organization Osaka National Hospital
Division name	1)Breast Surgery, 2) Department of surgery,Breast oncology
Zip code	606-8507
Address	1)54 Syogoin Kawahara-cho, Sakyu-ku, Kyoto , Japan
TEL	075-751-3660
Email	office@jbcrg.jp

Public contact
Name of contact person	1st name Jun Middle name Last name Fukase
Organization	Japan Breast Cancer Research Group (JBCRG)
Division name	Head office
Zip code	103-0016
Address	9-4-3F, Nihonbashikoamicho, Chuo-ku, Tokyo, Japan
TEL	03-6264-8873
Homepage URL	https://www.jbcrg.jp/
Email	office@jbcrg.jp

Sponsor
Institute	Japan Breast Cancer Research Group)
Institute
Department

Funding Source
Organization	Eisai Co., Ltd.
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)
Organization	N/A
Address	N/A
Tel	N/A
Email	N/A

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

独立行政法人国立病院機構北海道がんセンター（北海道） 新潟県立がんセンター新潟病院（新潟県） 公立大学法人　福島県立医科大学附属病院（福島県）　 筑波大学附属病院 （茨城県） 埼玉医科大学国際医療センター（埼玉県） 埼玉県立がんセンター（埼玉県） 千葉県がんセンター（千葉県） がん・感染症センター 都立駒込病院 （東京都） 国家公務員共済組合連合会 虎の門病院 （東京都） 公益財団法人 がん研究会有明病院 （東京都） 杏林大学医学部付属病院 （東京都） 地方独立行政法人神奈川県立病院機構 神奈川県立がんセンター（神奈川県） 京都大学医学部附属病院 （京都府） 独立行政法人 国立病院機構大阪医療センター（大阪府） 地方独立行政法人大阪府立病院機構 大阪府立成人病センター（大阪府） 地方独立行政法人広島市立病院機構 広島市立広島市民病院 （広島県） 広島大学病院 （広島県） 独立行政法人国立病院機構四国がんセンター（愛媛県） 熊本大学医学部附属病院（熊本県） 神戸市立医療センター中央市民病院（兵庫県）

Other administrative information
Date of disclosure of the study information	2016 Year 09 Month 15 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	100
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	No longer recruiting
Date of protocol fixation	2016 Year 06 Month 10 Day
Date of IRB	2016 Year 06 Month 10 Day
Anticipated trial start date	2017 Year 03 Month 09 Day
Last follow-up date	2024 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	2016 Year 07 Month 14 Day
Last modified on	2022 Year 01 Month 20 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026361

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

Contact us.