UMIN-CTR Clinical Trial

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

HER2 positive breast cancer

Classification by specialty

Hematology and clinical oncology	Surgery in general	Breast surgery

Classification by malignancy

Malignancy

Genomic information

YES

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

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

Study type

Interventional

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

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

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

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

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

Institute

Japan Breast Cancer Research Group (JBCRG)

Institute

Department

Personal name

Organization

Japan Breast Cancer Research Group (JBCRG)

Organization

Division

Category of Funding Organization

Self funding

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

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）

Date of disclosure of the study information

2009

Year

08

Month

31

Day

URL releasing protocol

https://upload.umin.ac.jp/cgi-bin/ctr/ctr_up_reg_f5.cgi

Publication of results

Published

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

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 related information

Registered date

2009

Year

08

Month

21

Day

Last modified on

2021

Year

08

Month

06

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002871