UMIN-CTR Clinical Trial

Basic information
Public title	A randomized study of Docetaxel + Cyclophosphamide (TC), 5-fluorouracil + Epirubicin + Cyclophosphamide (FEC)-TC and TC-FEC as preoperative chemotherapy for hormone receptor positive and HER2 negative primary breast cancer JBCRG-09
Acronym	JBCRG-09
Scientific Title	A randomized study of Docetaxel + Cyclophosphamide (TC), 5-fluorouracil + Epirubicin + Cyclophosphamide (FEC)-TC and TC-FEC as preoperative chemotherapy for hormone receptor positive and HER2 negative primary breast cancer JBCRG-09
Scientific Title:Acronym	JBCRG-09
Region	Japan

Condition
Condition	hormone receptor positive and HER2 negative primary breast cancer
Classification by specialty	Hematology and clinical oncology Surgery in general Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy and safety of 6 cycles of docetaxel and cyclophosphamide (TC), 3 cycles of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) followed by 3 cycles of TC (FEC-TC), and 3 cycles of TC followed by 3 cycles of FEC as preoperative chemotherapy in patients with hormone receptor positive and HER2 negative primary breast cancer randomized to receive either of these therapies
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	pathological complete rseponse rate
Key secondary outcomes	Safety,Overall response rate,Disease-free survival,Overall surviva, Clinical response evaluation using various diagnostic imaging techniques

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Cluster
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking
Concealment	Central registration

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	1)TC therapy group: 6 cycles of TC therapy TC therapy Docetaxel : 75 mg/m2, 1h, day1 Cyclophosphamide : 600 mg/m2, 15-30min, day1
Interventions/Control_2	2)FEC-TC therapy group: 3 cycles of FEC therapy followed by 3 cycles of TC therapy FEC therapy group Fluorouracil(5-FU) : 500 mg/m2, 15-30min, day1 Epirubicin (EPI) : 100 mg/m2, 5min, day1 Cyclophosphamide : 500 mg/m2, 15-30min, day1
Interventions/Control_3	3)TC-FEC therapy group: 3 cycles of TC therapy followed by 3 cycles of FEC therapy
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	70 years-old >=
Gender	Female
Key inclusion criteria	1)Female primary breast cancer patients who are diagnosed as invasive breast cancer by needle biopsy or tissue biopsy. 2)Resectable primary breast cancer (T1c-3 N0-1 M0) and tumor size is 7 cm or smaller. Multiple ipsilateral breast cancer is eligible when at least 1 lesion meets the eligible criteria. However, each lesion has to be histologically evaluated. 3)Status of ER and PgR are confirmed by immunohistochemical staining, and Estorogen receptor(ER) and/or Progesterone receptor(PgR) positive. 4)HER2 expression is confirmed by Immunohistochemistry (IHC or FISH); and IHC=0-1+, OR if IHC 2+ -> FISH negative. 5)Age between 20 years old and 70 years old 6)Performance status (PS) 0-1. 7)Results from a laboratory test meet the following (within 14days before registration): Leukocyte count is >=4000/mm3 and <=12 000/mm3 or neutrophil count is >=2000/mm3 Hemoglobin >=9.0g/dL Platelet >=100,000/mm3 AST and ALT <=x 2.5 of upper limit of normal (ULN) total bilirubin or direct bilirubin <=ULN Serum creatinine <=x 1.5 of ULN 8) Left ventricular ejection fraction (LVEF) is >=55% measured by echocardiography or MUGA scan. 9)No clinical abnormality by electrocardiography 10)No interstitial pneumonia or pulmonary fibrosis diagnosed by chest CT scan. 11)Evaluate images of the primary lesion before and after treatment by CT, MRI or ultrasound. The evaluation must be based on the same modality. 12)No previous treatments for breast cancer such as chemotherapy, hormone therapy, molecular target therapy, radiotherapy and immunotherapy. 13)Considered eligible to neoadjuvant chemotherapy based on decision of the attending physician after considering other treatments such as surgery, chemotherapy, hormone therapy. 14)Urinary or serum HCG negative when menopause is not confirmed (excluding patients underwent ovariectomy or hysterectomy). 15)Signed written informed consent
Key exclusion criteria	1)Hypersensitivity to any agents necessary in the planned treatment. 2)Poorly controlled complication (malignant hypertension, myocardial infarction within 6 months, congestive heart failure, coronary insufficiency, arrhythmia which requires treatment, infection and bleeding). 3)Fever with suspected infection. 4)Symptoms of varicella. 5)Pleural effusion or cardiac effusion which requires treatment. 6)Serious edema. 7)Serious peripheral neuropathy 8)Complication which requires prior treatment with corticosteroid. 9)Regular use of H2 blocker. 10)Has history of or receiving treatment for serious psychiatric disorder case. 11)Synchronous bilateral breast cancer excluding contralateral non-invasive cancer (DCIS/LCIS). 12)History of invasive breast cancer. 13)Multiple primary cancer .However, carcinoma in situ can be cured by local treatment is not included in multiple primary cancer. 14)History of multiple primary cancers in the past 5 years, excluding nonmelanoma skin cancer, cervical cancer, thyroid cancer, early gastric cancer and early colorectal cancer appropriately treated. 15)Prior treatment with anticancer case. 16)Women who are pregnant, lactating or with childbearing potential. 17)Ineligible based on decision of an investigator.
Target sample size	195

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 Hospital 2)Osaka National Hospital
Division name	1)Breast Surgery 2)Department of Surgery (mastology)
Zip code	540-0006
Address	1-14, 2-chome Hoenzaka, chuou-ku, Osaka-city, Osaka
TEL	06-6942-1331
Email	nmasuda@alpha.ocn.ne.jp

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

Sponsor
Institute	Japan Breast Cancer Research Group (JBCRG)
Institute
Department

Funding Source
Organization	Japan Breast Cancer Research Group (JBCRG)
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	JAPAN

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

IRB Contact (For public release)
Organization	JBCRG
Address	9-4-3F, Nihonbashikoamicho, Chuo-ku, Tokyo 103-0016, Japan
Tel	03-6264-8873
Email	office@jbcrg.jp

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	大阪医療センター(大阪府) 熊本大学医学部附属病院(熊本県） 群馬県立がんセンター(群馬県） 八尾市立病院(大阪府) 北海道がんセンター(北海道） 大阪労災病院(大阪府） 新潟県立がんセンター(新潟県） 虎の門病院(東京都） 広島大学病院(広島県） 杏林大学医学部附属病院（東京都） 小牧市民病院（愛知県） 兵庫医科大学(兵庫県） 大阪市立大学（大阪府） 及川病院(福岡県） 広島市民病院(広島県） 京都大学医学部附属病院(京都府) 中頭病院（沖縄県） 横浜旭中央総合病院(神奈川県） 九州がんセンター(福岡県） 長崎医療センター（長崎県）

Other administrative information
Date of disclosure of the study information	2010 Year 03 Month 03 Day

Related information
URL releasing protocol	https://upload.umin.ac.jp/cgi-bin/ctr/ctr_up_reg_f5.cgi
Publication of results	Published

Result
URL related to results and publications	NA
Number of participants that the trial has enrolled	195
Results	pCR (CpCR + ypN0) rates were 9.2%, 8.1%, and 15.9% in the FEC-TC, TC-FEC, and TC6 groups, respectively. ORRs were 72.8% in the FEC-TC group (CR 12.3%), 73.0% in the TCFEC group (CR 4.8%), and 75.4% in the TC6 group (CR15.4%). pCR rates in the three groups were similar, but the breast conservation rate was significantly higher in the TC6 group than in the others.
Results date posted	2021 Year 08 Month 18 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2020 Year 03 Month 13 Day
Baseline Characteristics	Hormone receptor-positive HER2-negative primary breast cancer
Participant flow	Patients were randomized to receive 6 cycles of TC (TC6), 3 cycles of FEC followed by 3 cycles of TC (FEC-TC), or 3 cycles of TC followed by 3 cycles of FEC (TC-FEC).
Adverse events	AEs of grade 3 or higher were 20.0%, 27.0%, and 20.3% in the FEC-TC, TC-FEC, and TC6 groups (p =0.569).
Outcome measures	Primary endpoint: pCR rate Secondary endpoint: Clinical responses, Safety
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2009 Year 08 Month 07 Day
Date of IRB	2009 Year 10 Month 08 Day
Anticipated trial start date	2009 Year 10 Month 09 Day
Last follow-up date	2017 Year 05 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	2010 Year 03 Month 02 Day
Last modified on	2021 Year 08 Month 18 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003873