UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000012179
Receipt number R000014038
Scientific Title Bevacizumab plus paclitaxel optimization study with interventional maintenance endocrine therapy in advanced or metastatic ER-positive HER2-negative breast cancer-BOOSTER trial, a multicenter randomized phase II study
Date of disclosure of the study information 2013/10/31
Last modified on 2022/07/16 20:17:56

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Basic information

Public title

Bevacizumab plus paclitaxel optimization study with interventional maintenance endocrine therapy in advanced or metastatic ER-positive HER2-negative breast cancer-BOOSTER trial, a multicenter randomized phase II study

Acronym

JBCRG-M04 (BOOSTER)

Scientific Title

Bevacizumab plus paclitaxel optimization study with interventional maintenance endocrine therapy in advanced or metastatic ER-positive HER2-negative breast cancer-BOOSTER trial, a multicenter randomized phase II study

Scientific Title:Acronym

JBCRG-M04 (BOOSTER)

Region

Japan


Condition

Condition

Hormone receptor positive, HER2 negative advanced or recurrence (metastatic) breast cancer

Classification by specialty

Hematology and clinical oncology Surgery in general Breast surgery

Classification by malignancy

Malignancy

Genomic information

YES


Objectives

Narrative objectives1

To compare continuing bevacizumab + paclitaxel or switching to bevacizumab + endocrine maintenance therapy followed by bevacizumab + paclitaxel, after 1st line induction therapy with bevacizumab + paclitaxel in
ER+HER2- advanced or metastatic breast cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase II


Assessment

Primary outcomes

Time to failure of strategy (TFS)

Key secondary outcomes

2y Overall Survival rate, Overall Survival, Progression Free Survival: PFS, QOL, Biomarker, Safety


Base

Study type

Interventional


Study design

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

NO

Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

weekly paclitaxel + bevacizumab

Interventions/Control_2

endocrine therapy + bevacizumab then back to weekly paclitaxel + bevacizumab therapy

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

20 years-old <=

Age-upper limit

75 years-old >=

Gender

Female

Key inclusion criteria

1. Histologically confirmed adenocarcinoma of the breast
2. Female aged 20-75 years old at getting informed consent
3. HER2 negative disease (IHC 0/1+ or 2+ with FISH negative)
4. Documented estrogen receptor (ER) positive (>=1% by IHC)
5. Inoperative locally advanced or metastatic breast cancer at enrolment
6. Performance status (ECOG): 0-1 at enrolment
7. Life expectancy of at least 3 months from enrolment
8. No prior systemic therapy for recurrent breast cancer (excluding hormone therapy)
9. No prior neo and/or adjuvant chemotherapy with taxane or adjuvant setting with a disease-free interval from completion of the taxane treatment to metastatic diagnosis of >= 12 months
10. Patients with measurable lesion regarding with RECIST criteria or who have evaluable lesion
11. Patients with only bone lesion will be acceptable if the osteolytic lesion has a measurable soft tissue component by MRI or CT
12. No influence on protocol treatment is considered in case prior therapy or examination.
13. Adequate following organ function within 2 weeks before starting treatment. The latest examination results should be adopted and blood transfusion or treatment of hematopoietic factor drugs is not allowed 2 weeks before examination.
- Absolute neutrophil count >= 1500 /mm3 or WBC count >= 3000 /mm3
- Platelets >=10 x 10000 /mm3
- Hb >= 9 g/dL
- Total bilirubin <= 1.5 mg/dL(except for constitutional jaundice)
- AST and ALT <= 100IU/L (<=200IU/L if liver metastasis)
- Serum creatinine <= 1.5 mg/dL
-Urine dipstick for proteinuria <= 1+
14. Written informed consent signed by patients before completing any treatment related procedure

Key exclusion criteria

(1)Prior therapy with bevacizumab
(2) Active infection requiring intrvenous antibiotics at enrollment or infection with active HBV and/or HCV.
(3) Pregnancy, lactetion or in case of potentialy pregnancy women Not mind contraception in trial period.
(4) Known hypersensitivity to bevacizumab or paclitaxel
(5) History of hemoptysis (>= 2.5mL of bright red blood per episord).
(6) Use of disulfiram,cyanamide, carmofur or procarbazine Hydrochloride
(7) Patients with CNS metastases (except for not symptomatic)
(8) Persistent Grade >= 2 sensory neuropathy at enrollment
(9) Grade 3 >= hypertension (>= 2 use of antihypertensive drug)
10) Evidence with arterial thromboembolism
(Cerebral infarction, Myocardial infarction) or history within 1 year prior to enrollment.
(11) Evidence withvenous thromboembolism (deep vein thrombosis, pulmonary embolism) or history within 1 year prior to enrollment.
(12) History of GI perforation and/or serious abdominal fistula within 1 year prior to enrollment
(13) Cases that the investigator judged as inappropriate as the subject of this clinical study

Target sample size

160


Research contact person

Name of lead principal investigator

1st name 1)Shigehira, 2)Masakazu
Middle name
Last name 1)Saji, 2)Toi

Organization

1) Fukushima Medical University
2) Kyoto University Graduate School of Medicine

Division name

1) Department of Medical Oncology, 2) Department of Breast Surgery

Zip code

1)960-1295,2)606-8507

Address

1) 1 Hikariga-oka, Fukushima City, 960-1295 JAPAN, 2) 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, JAPAN

TEL

024-547-1511

Email

ss-saji@wa2.so-net.ne.jp


Public contact

Name of contact person

1st name Jun
Middle name
Last name Fukase

Organization

Japan Breast Cancer Research Group (JBCRG)

Division name

Head office

Zip code

103-0016

Address

3rd Floor, Nihonbashikoamicho9-4, Chuo-ku, Tokyo 103-0016, JAPAN

TEL

03-6264-8873

Homepage URL

https://www.jbcrg.jp/

Email

office@jbcrg.jp


Sponsor or person

Institute

Japan Breast Cancer Research Group (JBCRG)

Institute

Department

Personal name



Funding Source

Organization

Chugai Pharmaceutical Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Fukushima Medical University Certified Review Board

Address

1 Hikariga-oka, Fukushima City, 960-1295 JAPAN

Tel

024-547-1825

Email

fmucrb@fmu.ac.jp


Secondary IDs

Secondary IDs

YES

Study ID_1

NCT01989780

Org. issuing International ID_1

ClinicalTrials.gov

Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

公立大学法人福島県立医科大学附属病院(福島県)、弘前市立病院(青森県)、久留米大学病院(福岡県)、京都大学医学部附属病院(京都府)、国家公務員共済組合連合会虎の門病院(東京都)、埼玉県立がんセンター(埼玉県)、愛知県がんセンター(愛知県)、横浜市立大学附属市民総合医療センター(神奈川県)、北海道大学病院(北海道)、北村山公立病院(山形県)、独立行政法人国立病院機構九州がんセンター(福岡県)、国立病院機構 長崎医療センター(長崎県)、広島市立広島市民病院(広島県)、札幌医科大学附属病院(北海道)、群馬県立がんセンター(群馬県)、東北大学病院(宮城県)、日本赤十字社和歌山医療センター(和歌山県)、旭川医科大学病院(北海道)、東京都立駒込病院(東京都)、宮崎県立宮崎病院(宮崎県)、独立行政法人国立病院機構四国がんセンター(愛媛県)、兵庫県立がんセンター(兵庫県)、国立病院機構呉医療センター中国がんセンター(広島県)、熊本大学病院(熊本県)、浜松医療センター(静岡県)、東京医科大学病院(東京都)、山形県立中央病院(山形県)、神戸市立医療センター中央市民病院(兵庫県)、独立行政法人地域医療機能推進機構 下関医療センター(山口県)、小牧市民病院(愛知県)、名古屋市立大学病院(愛知県)、静岡県立総合病院(静岡県)、岡山大学病院(岡山県)、東京医科大学八王子医療センター(東京都)、市立四日市病院(三重県)、国立大学法人岐阜大学医学部附属病院(岐阜県)、佐賀県医療センター好生館(佐賀県)、名古屋大学医学部附属病院(愛知県)、関西電力病院(大阪府)、国立病院機構 北海道がんセンター(北海道)、千葉県がんセンター(千葉県)、岩手医科大学附属病院(岩手県)、大崎市民病院(宮城県)、筑波大学附属病院(茨城県)、福山市民病院(広島県)、日本海総合病院(山形県)、熊本赤十字病院(熊本県)、聖マリアンナ医科大学病院(神奈川県)、JA広島総合病院(広島県)、岐阜市民病院(岐阜県)、伊勢崎市民病院(群馬県)、独立行政法人 国立病院機構 埼玉病院(埼玉県)、順天堂大学医学部附属順天堂医院(東京都)


Other administrative information

Date of disclosure of the study information

2013 Year 10 Month 31 Day


Related information

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTs021180026

Publication of results

Published


Result

URL related to results and publications

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00196-6/fulltext

Number of participants that the trial has enrolled

160

Results

Median TFS (time-to-failure of strategy) are 8.87 months in the wPTX + BV continued group, and 16.82 months in the maintenance endocrine + BV group, respectively (HR 0.51; p<0.001).
OS (overall survival) in both groups are similar, which means chemo-holiday with endocrine based therapy could be safely applied to ER+HER2-ABC/MBC after induction chemotherapy.
HRQoL seems to be better in endocrine + BV compared to chemotherapy continuous strategy.

Results date posted

2022 Year 07 Month 14 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2022 Year 04 Month 08 Day

Baseline Characteristics

wPTX + BV continue: 63 Age( mean 56.2 ) Menopause( Pre: 33.3%, Post: 63.5% ) PS( 0:81.0%, 1:19.0% )
endocrine + BV maintenance: 61 Age( mean 56.2 ) Menopause ( Pre:27.9%, Post:70.5% ) PS( 0:91.8%, 1:8.2% )

Participant flow

Following 4 to 6 cycles of paclitaxel + bevacizumab (wPTX + BV) therapy for ER-positive HER2-negative advanced/recurrent breast cancer (n=160), patients who responded to this therapy were randomized (n=125). 63 cases were in wPTX + BV continuous treatment group, and 62 cases were in endocrine + BV therapy switch group. Except for one unknown record case, all patients had protocol treatment.

Adverse events

The number and rate of major adverse events by group and grades are reported below.
1. All adverse events
(1) wPTX+BV therapy (63 patients)
All grade:59(93.7%) Grade3:50(79.4%) Grade4:5(7.9%)
(2) endocrine + BV therapy (61 patients)
All grade:51(83.6%) Grade3:35(57.4%) Grade4:5(8.2%)
(3) All (124 patients)
All grade:110(88.7%) Grade3:85(68.5%) Grade4:10(8.1%)
2. Hyper tension
(1) wPTX+BV therapy (63 patients)
All grade:39(61.9%) Grade3:24(38.1%) Grade4:1(1.6%)
(2) endocrine + BV therapy (61 patients)
All grade:38(62.3%) Grade3:20(32.8%) Grade4:2(3.3%)
(3) All (124 patients)
All grade:77(62.1%) Grade3:44(35.5%) Grade4:3(2.4%)
3. Decrease in neutrophil count
(1) wPTX+BV therapy (63 patients)
All grade:33(52.4%) Grade3:16(25.4%) Grade4:2(3.2%)
(2) endocrine + BV therapy (61 patients)
All grade:26(42.6%) Grade3:10(16.4%) Grade4:2(3.3%)
(3) All (124 patients)
All grade:59(47.6%) Grade3:26(21.0%) Grade4:4(3.2%)
4. Peripheral neuropathy
(1) wPTX+BV therapy (63 patients)
All grade:50(79.4%) Grade3:17(27.0%) Grade4:0(0.0%)
(2) endocrine + BV therapy (61 patients)
All grade:34(55.7%) Grade3:5(8.2%) Grade4:0(0.0%)
(3) All (124 patients)
All grade:84(67.7%) Grade3:22(17.7%) Grade4:0(0.0%)
5. Proteinuria
(1) wPTX+BV therapy (63 patients)
All grade:26(41.3%) Grade3:10(15.9%) Grade4:0(0.0%)
(2) endocrine + BV therapy (61 patients)
All grade:28(45.9%) Grade3:13(21.3%) Grade4:0(0.0%)
(3) All (124 patients)
All grade:54(43.5%) Grade3:23(18.5%) Grade4:0(0.0%)
6. Bleeding
(1) wPTX+BV therapy (63 patients)
All grade:19(30.2%) Grade3:0(0.0%) Grade4:0(0.0%)
(2) endocrine + BV therapy (61 patients)
All grade:24(39.3%) Grade3:0(0.0%) Grade4:0(0.0%)
(3) All (124 patients)
All grade:43(34.7%) Grade3:0(0.0%) Grade4:0(0.0%)

Outcome measures

(1)Primary endpoint: Time to failure of strategy(TFS)
Median TFS was 8.87 months in the wPTX + continued BV group and 16.82 months in the hormone + BV group. TFS was significantly prolonged in the hormone + BV group (HR 0.51; p<0.001).
(2)Secondary endpoint: Overall survival
There was no difference in OS between the wPTX + BV continuation group and the hormone + BV group.
(3)Secondary endpoint: HRQOL(Health-related QOL) FACT-B-TOI (improvement, deterioration)
HRQoL tended to be better in the hormone + BV therapy group compared to the wPTX + BV continuation group at 4 months and 1 year, although not significantly different.

Plan to share IPD

Deidetified patient data will be made available upon reasonable request.

IPD sharing Plan description



Progress

Recruitment status

Main results already published

Date of protocol fixation

2012 Year 10 Month 27 Day

Date of IRB

2013 Year 05 Month 25 Day

Anticipated trial start date

2014 Year 01 Month 28 Day

Last follow-up date

2019 Year 06 Month 30 Day

Date of closure to data entry

2019 Year 06 Month 30 Day

Date trial data considered complete

2019 Year 06 Month 30 Day

Date analysis concluded



Other

Other related information



Management information

Registered date

2013 Year 10 Month 31 Day

Last modified on

2022 Year 07 Month 16 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014038


Research Plan
Registered date File name

Research case data specifications
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Research case data
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