UMIN-CTR Clinical Trial

Basic information
Public title	A phase III randomized study of neoadjuvant chemotherapy including trastuzumab + cyclophosphamide + docetaxel in patients with operable HER2 positive breast cancer (JBCRG 10)
Acronym	JBCRG-10
Scientific Title	A phase III randomized study of neoadjuvant chemotherapy including trastuzumab + cyclophosphamide + docetaxel in patients with operable HER2 positive breast cancer (JBCRG 10)
Scientific Title:Acronym	JBCRG-10
Region	Japan

Condition
Condition	HER2 positive breast cancer
Classification by specialty	Hematology and clinical oncology Surgery in general Breast surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	The objective of the study is to investigate efficacy and safety of FEC therapy followed by TCH therapy, TCH therapy followed by FEC therapy and TCH therapy in an aim to improve pathological complete response (pCR) by neoadjuvant chemotherapy in operable HER2 positive breast cancer patients. After June 2011 the protocol has been amended and TCH group is only entered.
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, incidence of cardiac disorders, clinical response rate, overall survival, breast conservation rate and rate without axillary lymph node dissection

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	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)FEC-TCH therapy group: 4 cycles of FEC therapy * (5-fluorouracil (5-FU) + epirubicin (EPI) + cyclophosphamide (CPA)) followed by 4 cycles of TCH therapy ** (docetaxel (DTX) + cyclophosphamide (CPA) + trastuzumab (H)) *FEC regimen: 1 cycle is 3 weeks; 5-FU (500 mg/m2, q3w), epirubicin (100 mg/m2, q3w), cyclophosphamide (500 mg/m2, q3w) **TCH regimen: 1 cycle is 3 weeks; docetaxel (75 mg/m2, q3w), cyclophosphamide (600 mg/m2, q3w)
Interventions/Control_2	2)TCH-FEC therapy group: 4 cycles of TCH therapy** followed by 4 cycles of FEC therapy
Interventions/Control_3	3)TCH therapy group: 6 cycles of TCH 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)Invasive lesion of the primary lesion is confirmed as HER2 positive (IHC 3+ or FISH+). 4)Status of ER and PgR are confirmed by immunohistochemical staining. 5)Age between 20 years old and 70 years old 6)ECOG performance status (PS): 0-1 7)Results from a laboratory test meet the following: a)Leukocyte count is >=4000/mm3 and <=12 000/mm3 or neutrophil count is >=2000/mm3 b)Hemoglobin >=9.0g/dL c)Platelet >=100 000/mm3 d)AST and ALT <=x 2.5 of upper limit of normal (ULN) e)Bilirubin (total bilirubin or direct bilirubin) <=ULN f)Serum creatinine <=x 1.5 of ULN 8)Baseline left ventricular ejection fraction (LVEF) is >=55% measured by echocardiography or MUGA scan. 9)No QTc prolongation by electrocardiography (QTc is <=470 msec). 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. 11)Synchronous bilateral breast cancer excluding contralateral non-invasive cancer (DCIS/LCIS). 12)Multiple primary cancer or has history of multiple primary cancer in the past 5 years. However, carcinoma in situ can be cured by local treatment is not included in multiple primary cancer. 13)History of invasive breast 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 agents. 16)Cardiac disorder diagnosed by echocardiography. 17)Women who are pregnant, lactating or with childbearing potential. 18)Ineligible based on decision of an investigator.
Target sample size	180

Research contact person
Name of lead principal investigator	1st name Middle name Last name Masakazu Toi1), Norikazu Masuda2), Takayuki Ueno3)
Organization	1)Kyoto University Hospital, 2)Osaka National Hospital,3)Kyorin University Hospital
Division name	1)Breast Surgery, 2)Department of Surgery (mastology)3)Department of Breast Surgery
Zip code
Address	1) 54 Syougoinkawaracho, sakyou-ku, kyouto-City, Kyoto, 2) 1-14, 2-chome Hoenzaka, chuou-ku, Osaka-city, Osaka, 3)6-20-2,Shinkawa, Mitaka-shi, Tokyo
TEL	06-6942-1331
Email	nmasuda@alpha.ocn.ne.jp

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

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)、新潟県立がんセンター（新潟県）、大阪赤十字病院（大阪府）、大阪労災病院（大阪府）、広島市民病院（広島県）、熊本大学医学部附属病院（熊本県）、岩手医科大学（岩手県）、京都大学医学部附属病院（京都府）、群馬県立がんセンター（群馬県）、北海道がんセンター（北海道）、横浜旭中央総合病院（神奈川県）、虎の門病院（東京都）、兵庫医科大学（兵庫県）、九州がんセンター（福岡県）、筑波大学病院（茨城県）

Other administrative information
Date of disclosure of the study information	2009 Year 08 Month 31 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	https://academic.oup.com/jjco/article/50/1/3/5672700?login=true
Number of participants that the trial has enrolled	103
Results	Results: TCH arm: pCR (ypT0/is) rate was 46% (n = 59). Overall response rate was 86%. Breast-conservation rate was 59%, and the proportion of patients who had been planned for mastectomy before PST but received breast-conserving surgery was 33% (9/27 patients). DFS and OS at 3 years were 96.6% and 98.3%, respectively. No significant difference was observed in DFS between the pCR (ypT0/is) and non-pCR groups (P = 0.87).
Results date posted	2021 Year 08 Month 06 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2019 Year 12 Month 10 Day
Baseline Characteristics	Treatment-naive women with operable HER2-positive 8IHC 3+ or FISH+) invasive breast cancer
Participant flow	NA
Adverse events	Grade 3 or higher toxicity was seen in 45% in the TCH arm. Leucopenia and febrile neutropenia were the most frequently reported grade 3 or higher adverse events.
Outcome measures	Primary endpoint: pCR rate Secondary endpoints: Safety Overall response rate Disease-free survival (DFS) Overall survival (OS) Breast-conserving surgery rate
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2009 Year 07 Month 14 Day
Date of IRB	2009 Year 07 Month 31 Day
Anticipated trial start date	2009 Year 08 Month 01 Day
Last follow-up date	2018 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	2009 Year 08 Month 21 Day
Last modified on	2021 Year 08 Month 06 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002871