UMIN-CTR Clinical Trial

Recruitment status Completed
Unique ID issued by UMIN UMIN000002349
Receipt No. R000002854
Scientific Title Evaluation of Trastuzumab without Chemotherapy as a Postoperative Adjuvant Therapy in HER2 Positive Elderly Breast Cancer Patients: Randomized Controlled Trial
Date of disclosure of the study information 2009/09/01
Last modified on 2020/10/28 (Ver. 24)

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Basic information
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
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

Objectives
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

Assessment
Primary outcomes Disease-Free Survival (DFS)
Key secondary outcomes Overall Survival (OS), Relapse-free Survival (RFS), Safety, HRQOL, CGA, Cost Effectiveness Analysis

Base
Study type Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute RESPECT executive committee
Institute
Department

Funding Source
Organization Public Health Research Foundation
Organization
Division
Category of Funding Organization Non profit foundation
Nationality of Funding Organization Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
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
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
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

Other administrative information
Date of disclosure of the study information
2009 Year 09 Month 01 Day

Related information
URL releasing protocol http://www.csp.or.jp/
Publication of results Published

Result
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

Progress
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
Other related information

Management information
Registered date
2009 Year 08 Month 18 Day
Last modified on
2020 Year 10 Month 28 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002854