UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Randomized Multicenter Phase2 Trial of Neoadjuvant Paclitaxel followed by Fluorouracil,Epirubin,and Cyclophosphamide(FEC)with or without Estrogen Deprivation by LH-RH agonist or Aromatase Inhibitor in Breast Cancer larger than 2 cm.
Title of the study (Brief title)	A Randomized Multicenter Phase2 Trial of Neoadjuvant Paclitaxel followed by Fluorouracil,Epirubin,and Cyclophosphamide(FEC)with or without Estrogen Deprivation by LH-RH agonist or Aromatase Inhibitor in Breast Cancer larger than 2cm. (NACED Randomized Multicenter Phase2 Trial)
Region	Japan

Condition
Condition	Breast Cancer
Classification by specialty	Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To investigate if simultaneous addition of estrogen deprivation treatment by either aromatase inhibitor(AI) or LHRH-A in breast cancer patients increases pathological CR in preoperative systemic chemotherapy. In hormonal receptor positive breast cancers, the rate of pathological CR in Taxol followed by FEC100 with or without estrogen deprivation by either AI in postmenopausal or LHRH-A in premenopausal is investigated in a randomized P-2 fashion.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	The rate of pathological CR
Key secondary outcomes	The rate of breast conservation operation, side effect, response rate, disease free survival, overall survival

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	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	4
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Premenopausal patients; Chemotherapy+estrogen deprivation group 1)Eighty mg/m2 of Taxol once a week for 12 weeks are given intravenously,then 2)FEC100 ( 500mg/m2 of 5-FU, 100mg/m2 of epi-ADM, 500mg/m2 of CPA) is given once a three weeks for 12weeks. 3)3.75mg/body of LHRH-A once a month for 6 months is given subdermally initiated within 2 weeks of the first Taxol.
Interventions/Control_2	Premenopausal patients; Chemotherapy group 1)Eighty mg/m2 of Taxol once a week for 12 weeks are given intravenously, then 2)FEC100 ( 500mg/m2 of 5-FU, 100mg/m2 of epi-ADM, 500mg/m2 of CPA) is given once a three weeks for 12weeks.
Interventions/Control_3	Postmenopausal patients; Chemotherapy group 1)Eighty mg/m2 of Taxol once a week for 12 weeks are given intravenously,then 2)FEC100(500mg/m2 of 5-FU,100mg/m2 of epi-ADM, 500mg/m2 of CPA)is given once a three weeks for 12weeks. 3)Twenty-five mg a day of Exemestan is given orally initiated within 2 weeks of the first Taxol for consecutive 6 months until one day before the operation.
Interventions/Control_4	Postmenopausal patients Chemotherapy group 1)Eighty mg/m2 of Taxol once a week for 12 weeks are given intravenously,then 2)FEC100 ( 500mg/m2 of 5-FU, 100mg/m2 of epi-ADM, 500mg/m2 of CPA) is given once a three weeks for 12weeks
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	Inclusion Criteria Eligible patients should meet all of the followings. 1)Eligible patients have histologically confirmed breast cancer who have no metastatic lesions except axillary lymphnode(s). 2)Tumor is larger than 2cm by any means of diagnostic imaging. 3)Patients with Performance status of 0 or 1(ECOG). 4)Patients should be older than 20 yrs. 5)No history of previous treatment of the present illness (chemotherapy, hormonal therapy, irradiation or surgery). Hormone replacement therapy is allowed if it has been discontinued 6 months before the trial. 6)Normal organ function with the following values; 1.WBC; greater than 4,000/mm3 or Neutrophil;greater than 2,000/mm3 2.PLT;greater than 10,000/mm3 3.Hgb;greater than 9.0g/dl 4.AST and ALT;no more than twice of the normal limit set by each insutitute. 5.T Bil.;no more than x 1.25 times of the normal limit set by each institute 6.Serum creatinine;no more than 1.5 times of the normal limit set by each institute. 7.Ejection fraction (EF) : greater than 60percent 8.ECG;normal without serious heart disease and arrhythmia. 7)Obtained written informed consent.
Key exclusion criteria	Exclusion Criteria 1)Previous history of treatment with taxol, Anthracyclines and hormonal treatment. 2)Infection, uncontrollable diabetes mellitus, severe heart disease, angina with poor control, myocardial infarction within 6 months, active ulcers, multiple cancers, severe neuropathy or any other severe complications. 3)interstitial pneumonia and lung fibrous disease which needs treatment. 4)liver cirrhosis. 5)stage-4 disease with metastasis. 6)Pleural effusion, ascites, pericardial effusion. 7)Coagulopathy including DIC. Pregnancy , possibility of pregnancy and breast feeding. 8)History of severe allergic reactions. 9)allergy to Clemophor. 10)allergic to TXL, 5FU, EpiADM, CPM, LHRH-A(premenopausal), exemestan (postmenopausal). 11)allergic to alcohol. 12)active multiple malignancies. 13)patients judged to be inadequate to accrue
Target sample size	120

Research contact person
Name of lead principal investigator	Jyunji Matsuoka M.D.,Ph.D.
Organization	Okayama University Graduate School of Medicine and Dentistry and Pharmaceutical Science
Division name	Department of Gastroenterological Surgery Transplant and Surgical Oncology
Address	2-5-1 Shikata-cho,Okayama 700-8558,JAPAN
TEL	086-235-7257
Email

Public contact
Name of contact person	Jyunji Matsuoka M.D.,Ph.D.
Organization	The FIRST
Division name	Department of Gastroenterological Surgery Transplant and Surgical Oncology, Okayama University
Address	2-5-1 Shikata-cho,Okayama 700-8558,JAPAN
TEL	086-235-7257
Homepage URL
Email	doumon@cc.okayama-u.ac.jp

Sponsor
Institute	THE FIRST
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor	Hirosima city Hosp.Chugoku central Hosp.Kagawa Rosai Hosp.Himeji Red Cross Hosp.Okayama Saiseikai Gen.HP et al.
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

Other administrative information
Date of disclosure of the study information	2007 Year 06 Month 30 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2007 Year 02 Month 01 Day
Anticipated trial start date	2007 Year 04 Month 01 Day
Last follow-up date	2017 Year 06 Month 20 Day
Date of closure to data entry	2017 Year 06 Month 20 Day
Date trial data considered complete	2017 Year 06 Month 20 Day
Date analysis concluded	2017 Year 06 Month 20 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results
Results	The primary endpoint was the pathological complete response (pCR) rate after neoadjuvant therapy. Twenty-eight patients were randomized. There were no significant differences in pCR rate between the concurrent group (12.5%;2/16) and the chemotherapy alone group (8.3%;1/12). Tumor size after therapy was significantly reduced in the concurrent therapy group (p=0.035), but not in the chemotherapy-alone group (p=0.622). Neoadjuvant chemotherapy with concurrent hormone therapy provided no significant improvement in pCR rate in ER-positive breast cancers. These preliminary results should be followed up by further studies.
Other related information

Management information
Registered date	2007 Year 06 Month 26 Day
Last modified on	2017 Year 06 Month 20 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000856