UMIN-CTR Clinical Trial

Public title

Efficacy study of sequential therapy with anthracycline, taxane, and eribulin in patients with HER2-negative locally advanced breast cancer (JBCRG-17)

Acronym

JBCRG-17

Scientific Title

Efficacy study of sequential therapy with anthracycline, taxane, and eribulin in patients with HER2-negative locally advanced breast cancer (JBCRG-17)

Scientific Title:Acronym

JBCRG-17

Region

Japan

Condition

Patients with HER2-negative, Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC locally advanced infiltrating breast cancer who have no prior treatment

Classification by specialty

Breast surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Evaluate the clinical response rate of sequential therapy with anthracycline, taxane, and eribulin in patients with HER2-negative locally advanced breast cancer. In addition, evaluate the histological effect, safety, and clinical efficacy. The clinical efficacy endpoints include the rate of radical surgery and breast-conserving surgery, survival period without metastasis, and overall survival period. In additional study, relationship between anticancer efficacy of eribulin and biological characteristics of cancer tissues are evaluated using molecular biological and biological methods.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase II

Primary outcomes

The clinical response rate of sequential therapy with anthracycline, taxane, and eribulin

Key secondary outcomes

(1) The histological response rate of sequential therapy with anthracycline, taxane, and eribulin.
(2) Clinical efficacy, rate of radical surgery, and rate of breast-conserving surgery.
(3) Safety evaluation (occurrence of adverse events)
(4) Exploration of clinicopathological and molecular biological markers related to prediction of cytoreductive effects.
(5) Overall survival and recurrence-free survival
(6) Clinical efficacy of eribulin after the treatment with anthracycline and taxane.

Exploratory endpoints: Exploratory assessment of differences in response rate of eribulin with differences in sequence of administration of anthracycline and taxane.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Sequential concomitant use of eribulin

Interventions/Control_2

Interventions/Control_3

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) Women at least 20 years of age but not older than 70
2) ECOG performance status (PS) is 0 to 1.
3) Locally advanced breast cancer of Stage IIIA (T2-3 and N2 only), stage IIIB, and Stage IIIC.
4) Histologically diagnosed with infiltrating breast cancer.
5) HER2 negative (1+ or 0 with IHC method. In the case of 2+ with IHC method, no amplification of HER2 gene should be observed in FISH or DISH method. Can be judged with FISH/DISH method alone, without IHC test.)
6) The regimen of this clinical study (anthracycline-taxane-eribulin) was indicated by mutual consent of primary physician and study center conference, considering the other treatments such as surgery, radiation therapy, and other systemic drug therapy.
7) Conducting imaging analysis of original lesion using MRI, CT, or breast ultrasonography prior, during, and after the treatment is possible (if the patient is allergic to contrast agent, conducting only breast ultrasonography is acceptable).
8) No prior treatment of breast cancer (chemotherapy, hormone therapy, molecular target therapy, radiation therapy, and immune therapy).
9) Patients who can take drug therapy with anthracycline and taxane and plan to take 2 to 4 courses of each treatment.
10) Main organ function (bone marrow, heart, liver, kidney, etc.) is not impaired. The values of laboratory findings within 28 days prior to the registration meet all of the followings.
(1) neutrophil count: =>1,500/mm3
(2) platelet count: =>100,000 mm3
(3) hemoglobin: =>9.0 g/dL
(4) total bilirubin: <=2.0 mg/dL
(5) AST (GOT), ALT (GPT): <=100IU
(6) serum creatinine <=1.5 mg/dL
(11) Patients with life expectancy of 12 months or longer from the initial registration.
(12) Patients without clinical problems in electrocardiogram.
(13) Patients who submitted written informed consent signed by the patient.

Key exclusion criteria

1) Patients with coexisting active infection or cases with pyrexia suspected of infection.
2) Cases with diarrhea (watery feces), intestinal paralysis, and intestinal obstruction.
3) Cases of fresh bleeding from gastrointestinal tract.
4) Cases with serious drug allergy.
5) Cases with serious renal disorder and hepatic disorder (jaundice).
6) Cases with clear indications of interstitial pneumonia or pulmonary fibrosis in chest X-ray.
7) Cases with large pleural/peritoneal effusion (patients required drainage)
8) Patients with difficult-to-control concomitant symptoms (hypertension with systolic/diastolic =>180/110 mmHg, cardiac infarction within 6 months, congestive heart failure, hepatic failure, arrhythmia that requires treatment, moderate cardiac valvulopathy, infection, hemorrhagic tendency, brittle diabetes mellitus, dyspnea at rest, long term oxygen therapy, serious edema, serious peripheral neuropathy, etc.)
9) Patients with cardiac dysfunction of NYHA Class III or IV.
10) Cases with continuous systemic administration (oral or intravenous) of steroid.
11) Pregnant patients or patients with possible pregnancy.
12) Active multiple primary cancer (Simultaneous multiple primary cancer and nonsimultaneous multiple primary cancer with disease-free interval of 5 years or shorter. Carcinoma in situ judged as treatable with local treatment or lesions of intramucosal carcinoma are not included in active multiple primary cancer.)
13) Cases with preexisting condition of psychiatric disorder or central nervous system disorder.
14) Cases that the investigator (subinvestigator) judged as inappropriate as the subject of this clinical study.

Target sample size

60

Name of lead principal investigator

1st name	1)Yoshinori 2) Norikazu
Middle name
Last name	1)Ito 2) Masuda

Organization

Cancer Institute Hospital, Japanese Foundation for Cancer Research / Osaka National Hospital

Division name

Breast Medical Oncology, Breast Oncology Center / Dept, of Surgery, Breast Oncology Unit

Zip code

135-8550

Address

3-8-31, Ariake, Koto-ku, Tokyo, JAPAN

TEL

(03)3520-0111

Email

yito@jfcr.or.jp

Name of contact person

1st name	Jun
Middle name
Last name	Fukase

Organization

JBCRG (Japan Breast Cancer Research Group)

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

Institute

JBCRG (Japan Breast Cancer Research Group)

Institute

Department

Personal name

Organization

JBCRG (Japan Breast Cancer Research Group)

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

N/A

Address

N/A

Tel

N/A

Email

N/A

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

愛知県がんセンター中央病院（愛知県）、九州がんセンター（福岡県）、広島市立広島市民病院（広島県）、がん研有明病院（東京都）、大阪労災病院（大阪府）、大分県立病院（大分県）、八尾市立病院（大阪府）、長崎大学病院（長崎県）、順天堂大学医学部附属順天堂医院（東京都）、相良病院（鹿児島県）

Date of disclosure of the study information

2012

Year

12

Month

28

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://doi.org/10.1007/s10549-021-06396-0

Number of participants that the trial has enrolled

53

Results

The overall clinical RR was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. 30 % (8/26) of patients had PD in the E phase, 6 of whom
had achieved cCR/PR in the AT phase.

Results date posted

2021

Year

11

Month

09

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2021

Year

09

Month

23

Day

Baseline Characteristics

HER2-negative, locally advanced breast cancer

Participant flow

Single-arm, Phase II study. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection.

Adverse events

Reported grade >= 3 AEs related to E were neutropenia (42%), WBC count
decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%).

Outcome measures

Primary endpoint
Response rate of Sequential administration of eribulin after the A/T-regimen.
Secondary endpoint
Pathological RR and Safety

Plan to share IPD

IPD sharing Plan description

Recruitment status

Terminated

Date of protocol fixation

2012

Year

12

Month

07

Day

Date of IRB

2012

Year

12

Month

07

Day

Anticipated trial start date

2012

Year

12

Month

07

Day

Last follow-up date

2019

Year

05

Month

27

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

12

Month

26

Day

Last modified on

2021

Year

11

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011264