UMIN-CTR Clinical Trial

Public title

Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with tri-weekly docetaxel (D) followed by doxorubicin, 5-fluorouracil, and cyclophosphamide (FEC) or docetaxel with concurrent use of capecitabine (TX) followed by doxorubicin, cyclophosphamide, and capecitabine (CEX) in women with locally advanced triple-negative breast cancer

Acronym

Phase II trial to evaluate the feasibility of neoadjuvant chemotherapy with docetaxel with concurrent use of capecitabine (TX) followed by doxorubicin, cyclophosphamide, and capecitabine (CEX) for triple-negative breast cancer

Scientific Title

Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with tri-weekly docetaxel (D) followed by doxorubicin, 5-fluorouracil, and cyclophosphamide (FEC) or docetaxel with concurrent use of capecitabine (TX) followed by doxorubicin, cyclophosphamide, and capecitabine (CEX) in women with locally advanced triple-negative breast cancer

Scientific Title:Acronym

Phase II trial to evaluate the feasibility of neoadjuvant chemotherapy with docetaxel with concurrent use of capecitabine (TX) followed by doxorubicin, cyclophosphamide, and capecitabine (CEX) for triple-negative breast cancer

Region

Japan

Condition

Untreated women with triple negative breast cancer (T1c-4NxM0)

Classification by specialty

Breast surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

We planned this trial to evaluate the effect and safety of new regimen, three cycles of docetaxel with capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX). We compare this regimen to the factually standard regimen: four cycles of docetaxel (D) followed by four cycles of cyclophosphamide, 5-fluorouracil, and epirubicin, (CEF) as neoadjuvant therapy of triple negative locally advanced breast cancer.
The challenging regimen in this trial, TX-CEX, was firstly shown in FIN-XX trial (2012). It was revealed that TX-CEX improved breast cancer specific survival and recurrent free survival especially in triple negative disease. In addition, this regimen is shorter for 6 weeks in compared with standard regimen, D-CEF.
We evaluate the feasibility of this regimen in neoadjuvant chemotherapy for triple negative breast cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

Rate of pathological complete response

Key secondary outcomes

Safety; was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, and chemotherapy doses were modified based on toxicity observed.
Overall response rate: was objective response rate according to RECIST version 1.1.
Disease free survival; which was defined as the time interval between random assignment and date of diagnosis of invasive breast cancer recurrence (local or distant) or death if the patient died before recurrence. Contralateral breast cancers and second cancers were not counted as DFS events.
Overall survival; which was defined as the time from random assignment to death.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

challenging arm received three cycles of docetaxel plus capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX). TX comprised capecitabine 900mg/m2 given orally twice per day on days 1 to 15 and docetaxel 60mg/m2 administered as a 1-hour intravenous infusion on day 1 of every 3-week cycle. CEX consisted of intravenous cyclophosphamide 600mg/m2 and epirubicin 75mg/m2 administered on day1 and oral capecitabine 900mg/m2 given twice per day on days 1 to 15 every 3 weeks.

Interventions/Control_2

standard arm received four cycles of docetaxel (T; 75 mg/m2 as a 1-hour intravenous infusion on day 1 of every 4-week cycle) followed by four cycles of cyclophosphamide (500 mg/m2), epirubicin (100 mg/m2), and fluorouracil (500 mg/m2; CEF), all administered on day 1 of each 4-week cycle.

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

65

years-old

>

Gender

Female

Key inclusion criteria

Disease-Specific Inclusion Criteria
1. Histologically or cytologically confirmed invasive carcinoma of the breast, and candidate for chemotherapy.
2. Tumor is radically resectable (T1c-T3, Nx, M0), and its maximum axis is no more than 7cm. If patient has multiple lesions, all of them must meet this criteria, and be confirmed malignancy by pathological examination).
There is at least one primary lesion, whose size could be assessed and measured by contrast-enhanced MRI at both time pre- and post-chemotherapy.
3. ER-negative and HER2-negative (FISH-negative or IHC 0-1+) were confirmed by each center's laboratory.
General Inclusion Criteria
4. Age >= 20 years, <65.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
6. Left Ventricular Ejection Fraction (LVEF) >= 50% at baseline (within 28 days of randomization) as determined by ECHO.
7. For women of childbearing potential, agreement to use an effective form of contraception (patient and/or partner, e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of study treatment and for 6 months after the last dose of study treatment.
8. Signed, written informed consent (approved by the Institutional Review Board or Independent Ethics Committee) obtained prior to any study procedure.

Key exclusion criteria

Cancer-Related Exclusion Criteria
1. History of anticancer therapy for breast cancer.
This includes any EGFR or anti-HER2 agents or vaccines, cytotoxic chemotherapy, or more than one prior hormonal regimen for breast cancer.
2. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma, thyroid cancer, early stage stomach, or colon cancer.
3. Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) or unstable angina
4. History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia). History of myocardial infarction within 6 months of randomization.
5. Current dyspnea at rest due to complications of interstitial pneumonia, or other diseases that require continuous oxygen therapy
General Exclusion Criteria
6. Inadequate organ function, evidenced by the following laboratory results within 28 days prior to randomization:
Absolute neutrophil count < 1,500 cells/mm3
Platelet count < 100,000 cells/mm3
Hemoglobin < 9 g/dL
Total bilirubin > upper limit of normal (ULN)
AST (SGOT) and ALT (SGPT) > 2.5 x ULN
Serum creatinine > 2.0 mg/dL
7. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)
8. Pregnant or lactating women
9. History of receiving any investigational treatment within 28 days of randomization
10. Receipt of intra-venous antibiotics for infection within 14 days of randomization
11. Current chronic daily treatment with corticosteroids (dose of > 10 mg per day methylprednisolone equivalent)
12. Known hypersensitivity to any of the study drugs
13. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Target sample size

84

Name of lead principal investigator

1st name
Middle name
Last name	Naoki Watanabe

Organization

Japanese Red Cross Society Himeji Hospital

Division name

Breast Surgery

Zip code

Address

1-12-1, Shimoteno, Himeji, Hyogo, 670-8540

TEL

079-294-2251

Email

n-watanabe@hrc-hp.com

Name of contact person

1st name
Middle name
Last name	Yukari Fujikado

Organization

Japanese Red Cross Society Himeji Hospital

Division name

Clinical Trial Manegement Office

Zip code

Address

1-12-1, Shimoteno, Himeji, Hyogo, 670-8540

TEL

079-294-2251

Homepage URL

Email

chiken@himeji.jrc.or.jp

Institute

Japanese Red Cross Society Himeji Hospital

Institute

Department

Personal name

Organization

Self funding

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

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

姫路赤十字病院

Date of disclosure of the study information

2015

Year

10

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2012

Year

04

Month

01

Day

Date of IRB

Anticipated trial start date

2012

Year

04

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

08

Month

19

Day

Last modified on

2017

Year

08

Month

29

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021098