UMIN-CTR Clinical Trial

Recruitment status Main results already published
Unique ID issued by UMIN UMIN000012179
Receipt No. 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 (Ver. 28)

* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments

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
Institute Japan Breast Cancer Research Group (JBCRG)
Institute
Department

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
URL(English) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014038