UMIN-CTR Clinical Trial

Public title

Evaluation of Trastuzumab without Chemotherapy as a Postoperative Adjuvant Therapy in HER2 Positive Elderly Breast Cancer Patients: Randomized Controlled Trial

Acronym

N-SAS BC07/RESPECT

Scientific Title

Evaluation of Trastuzumab without Chemotherapy as a Postoperative Adjuvant Therapy in HER2 Positive Elderly Breast Cancer Patients: Randomized Controlled Trial

Scientific Title:Acronym

N-SAS BC07/RESPECT

Region

Japan

Condition

HER2 positive primary breast cancer in elderly

Classification by specialty

Hematology and clinical oncology	Surgery in general	Breast surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To investigate clinical positioning between trastuzumab (Herceptin) monotherapy (H group) and combination therapy of trastuzumab and chemotherapy (H+CT group) based on a randomized controlled trial in women over 70 years with human epidermal growth factor

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase III

Primary outcomes

Disease-Free Survival (DFS)

Key secondary outcomes

Overall Survival (OS), Relapse-free Survival (RFS), Safety, HRQOL, CGA, Cost Effectiveness Analysis

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

H group (trastuzumab monotherapy group)
- Trastuzumab: 1-year treatment
- Loading dose, 8 mg/kg; from 2nd dose, 6 mg/kg; iv inj, qw, 18 times

Interventions/Control_2

H+CT group (combination therapy of trastuzumab and chemotherapy)
- Chemotherapy: 12 to 24 weeks
- Select chemotherapy from certain regimens (PTX, DTX, TC, AC, EC, FEC, CMF and TCb (CBDCA)) based on decision of a physician or a patient. Initiate administration of trastuzumab after completion of chemotherapy as a sequential combination. However, concomitant administration is allowed when combining trastuzumab with PTX, DTX and CMF. In cases of TCb (CBDCA), trastuzumab is used concomitant administration.

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

70

years-old

<=

Age-upper limit

81

years-old

>

Gender

Female

Key inclusion criteria

1. Histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer.
2. Stage: 1 (tumor size [pT] > 0.5 cm), 2A, 2B or 3A/ M0
3. Female between 69 and 81 years old
4. Primary region is HER 2 positive: either 3+ overexpression by IHC or positive by FISH
5. Baseline left ventricular ejection fraction (LVEF) is >=55% measured by echocardiography or MUGA scan within 4 weeks before registration.
6. PS: 0-1 (ECOG)
7. Sufficient organ function meeting following criteria within 4 weeks before registration:
(1) Leukocyte >=2500 mm3
(2) Neutrophil >=1500 mm3
(3) Platelet >=100 000 mm3
(4) Serum total bilirubin >=2.0 x upper limit of normal (ULN)
(5) ALT (GPT) or AST (GOT) >=2.5 x ULN
(6) Serum creatinine >=2.0 x ULN
(7) ALP >=2.5 x ULN
8. No previous endocrine therapy or chemotherapy for breast cancer
9. Signed written informed consent

Key exclusion criteria

1. Active multiple primary cancer (synchronous multiple primary cancer and invasive cancer of other organs)
2. Postoperative histological axillary lymph node metastasis >=4
3. Axillary lymph node is not histologically evaluated
4. Histologically confirmed positive margin in breast conservation surgery (evaluation of margin status is based on policy of site)
5. History of drug-related allergy which could hinder planned treatment
6. Any history or complication of following cardiac disorders
- History of congestive heart failure, cardiac infarction
- Complication requires treatment such as: ischemic cardiac disorder, arrhythmia, valvular heart disease
7. Poorly controlled hypertension (ex. Systolic arterial pressure >=180 mmHg or diastolic blood pressure >=100 mmHg)
8. Poorly controlled diabetes
9. Continuous visit to a medial institution is considered difficult due to deterioration of activity of daily living (ADL)
10. Difficult to participate in the trial because of psychiatric disorder or psychiatric symptoms
11. Ineligible to the trial based on decision of an investigator

Target sample size

300

Name of lead principal investigator

1st name	Masataka
Middle name
Last name	Sawaki

Organization

Aichi Cancer Center Hospital

Division name

Department of Breast Oncology

Zip code

464-8681

Address

1-1 Kanokoden Chikusa-ku, Nagoya, 464-8681 Japan

TEL

052-762-6111

Email

m-sawaki@aichi-cc.jp

Name of contact person

1st name	Akira
Middle name
Last name	Yamao

Organization

Public Health Research Foundation

Division name

Comprehensive Support Project for Clinical Research

Zip code

169-0051

Address

1-1-7, Nishiwaseda, Shinjyuku-ku, Tokyo, 169-0051 Japan

TEL

03-5287-2633

Homepage URL

http://www.csp.or.jp/

Email

support@csp.or.jp

Institute

RESPECT executive committee

Institute

Department

Personal name

Organization

Public Health Research Foundation

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Aichi Cancer Center

Address

1-1 Kanokoden Chikusa-ku, Nagoya, 464-8681 Japan

Tel

052-762-6111

Email

m-sawaki@aichi-cc.jp

Secondary IDs

YES

Study ID_1

NCT01104935

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

愛知県がんセンター愛知病院、愛知県がんセンター中央病院、青森県立中央病院、青森市民病院、安城更生病院、伊勢崎市民病院、岩手医科大学附属病院、うえお乳腺外科、大分県立病院、大垣市民病院、大阪医科大学附属病院、大阪医療センター、大阪国際がんセンター、大阪市立大学医学部附属病院、大阪ブレストクリニック、大阪労災病院、太田記念病院、岡山赤十字病院、岡山大学病院、香川県立中央病院、金沢大学附属病院、亀田総合病院（亀田メディカルセンター）、がん研究会有明病院、関西医科大学附属枚方病院、北里大学病院、北村山公立病院、岐阜県総合医療センター、九州がんセンター、京都桂病院、杏林大学医学部付属病院、近畿大学医学部附属病院、熊本大学医学部附属病院、群馬県立がんセンター、群馬大学医学部附属病院、KKR札幌医療センター斗南病院、県立広島病院、国立がん研究センター東病院、済生会新潟第二病院、済生会兵庫県病院、埼玉県立がんセンター、さいたま赤十字病院、札幌医科大学附属病院、札幌ことに乳腺クリニック、JA長野厚生連、佐久総合病院、JA広島総合病院、JA北海道厚生連旭川厚生病院、JCHO久留米総合病院、滋賀医科大学医学部附属病院、四国がんセンター、静岡県立総合病院、静岡市立清水病院、自治医科大学附属病院、渋川医療センター、下関医療センター、順天堂大学医学部附属順天堂医院、昭和伊南総合病院、市立東大阪医療センター、市立四日市病院、聖マリアンナ医科大学病院、千葉県がんセンター、千葉大学医学部附属病院、筑波大学附属病院、手稲渓仁会病院、東北大学病院、鳥取大学医学部附属病院、豊川市民病院、虎の門病院、都立駒込病院、名古屋市立大学病院、名古屋セントラル病院、名古屋大学医学部附属病院、名古屋第二赤十字病院、那覇西クリニック、新潟県立がんセンター新潟病院、新潟市民病院、新潟大学医歯学総合病院、日本海総合病院、日本生命済生会付属日生病院、博愛会相良病院、浜松医療センター、東札幌病院、兵庫医科大学病院、兵庫県立がんセンター、弘前市立病院、広島市立安佐市民病院、広島市立広島市民病院、広島大学病院、福岡県済生会福岡総合病院、福岡大学病院、藤田保健衛生大学病院、ベルランド総合病院、北海道がんセンター、北海道大学病院、三重大学医学部附属病院、三豊総合病院、八尾市立病院、山口大学医学部附属病院、山梨県立中央病院、りんくう総合医療センター

Date of disclosure of the study information

2009

Year

09

Month

01

Day

URL releasing protocol

http://www.csp.or.jp/

Publication of results

Published

URL related to results and publications

https://ascopubs.org/doi/full/10.1200/JCO.20.00184

Number of participants that the trial has enrolled

275

Results

Three-year DFS was 89.5% with trastuzumab monotherapy vs. 93.8% with trastuzumab + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; P = .51). At 3 years, restricted mean survival time differed by -0.39 months. The primary objective of noninferiority was not met. However, the observed loss of survival without chemotherapy was < 1 month at 3 years. In light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.

Results date posted

2020

Year

10

Month

28

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Patients aged 70-80 years with surgically treated human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer

Participant flow

This study was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients received trastuzumab monotherapy or trastuzumab + chemotherapy.

Adverse events

Common AEs were anorexia (7.4% vs. 44.3%; P < .0001) and alopecia (2.2% vs. 71.7%; P < .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% (P = .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively.
Clinically meaningful health-related quality of life (HRQoL) deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy vs. 48% for trastuzumab + chemotherapy; P = .016) and at 1 year (19% v 38%; P = .009).

Outcome measures

The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR).
Secondary end points: RFS, AEs, HRQoL

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2009

Year

07

Month

01

Day

Date of IRB

2009

Year

10

Month

19

Day

Anticipated trial start date

2009

Year

10

Month

28

Day

Last follow-up date

2017

Year

10

Month

31

Day

Date of closure to data entry

2018

Year

10

Month

12

Day

Date trial data considered complete

2018

Year

10

Month

15

Day

Date analysis concluded

Other related information

Registered date

2009

Year

08

Month

18

Day

Last modified on

2020

Year

10

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002854