UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000022256 |
|---|---|
| Receipt number | R000024427 |
| Scientific Title | A multicenter, cooperative, randomized, comparative study regarding the efficacy of denosumab for bone loss related to postoperative endocrine therapy in postmenopausal patients with hormone-sensitive breast cancer |
| Date of disclosure of the study information | 2016/07/01 |
| Last modified on | 2025/11/19 17:52:02 |
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Basic information
Public title
A multicenter, cooperative, randomized, comparative study regarding the efficacy of denosumab for bone loss related to postoperative endocrine therapy in postmenopausal patients with hormone-sensitive breast cancer
Acronym
The efficacy of the use of denosumab in the prevention of AI-induced bone loss in postmenopausal patients
Scientific Title
A multicenter, cooperative, randomized, comparative study regarding the efficacy of denosumab for bone loss related to postoperative endocrine therapy in postmenopausal patients with hormone-sensitive breast cancer
Scientific Title:Acronym
The efficacy of the use of denosumab in the prevention of AI-induced bone loss in postmenopausal patients
Region
| Japan |
Condition
Condition
Breast Cancer
Classification by specialty
| Breast surgery |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
To evaluate inhibitory effects of denosumab in the prevention of aromatase inhibitor-induced bone loss to postmenopausal patients with stage I-IIIA hormone-sensitive breast cancer who will intake an aromatase inhibitor as postoperative endocrine therapy.
Basic objectives2
Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase
Assessment
Primary outcomes
Rate of change in the bone mineral density (BMD) for the lumbar vertebrae (L1-L4) on dual-energy X-ray absorptiometry (DXA) 12 months after the start of this study
Key secondary outcomes
1) Rate of change in the BMD for the lumbar vertebrae (L1-L4) on DXA: After 2, 3, 4, and 5 years
2) Rate of change in the BMD for the femoral neck: After 12 months and 2/3/4/5 years
3) Rate of change in the BMD for the radius (an ultrasonic bone densimeter is used): After 2 and 4 weeks, every 4 weeks thereafter (for 2 years after registration)(only institutions in which ultrasonic bone densimeters are used)
4) Changes in Ca and bone metabolism markers (TRAP5b, bone-specific alkaline phosphatase (BSAP), blood pentosidine)
5) Appearance of morbid fracture within 3 years
6) Disease-free survival
7) Overall survival
8) Appearance (type, incidence) of adverse events (such as hypocalcemia and necrosis of the jaw)
9) Quality of life (QOL), Japanese version Euro-Qol (EQ-5D-5L)
Base
Study type
Interventional
Study design
Basic design
Parallel
Randomization
Randomized
Randomization unit
Individual
Blinding
Open -no one is blinded
Control
No treatment
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
2
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
intake AI for 5 years and have subcutaneousinjection of denosumab every 6 months
Interventions/Control_2
only intake AI for 5 years
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
| Not applicable |
Gender
Female
Key inclusion criteria
1) Patients with infiltrative breast cancer, aged 20 and older years, meeting the following definitions:
-Those pathologically diagnosed with stage I, II, or IIIA breast cancer
-Those who underwent appropriate surgery, such as mastectomy and breast-preserving surgery
2) Estrogen receptor or progesterone receptor positive patients on immunohistochemical staining
3) Females meeting one of the following criteria for menopause:
-Those, aged 55 and older years, without menstruation
-Those, aged younger than 55 years, with amenorrhea for 12 and more months, or those diagnosed with menopause by attending physicians based on the FSH and estradiol levels
-Those who underwent bilateral oophorectomy
4) Patients in whom the BMD for the lumbar vertebrae (L1-L4) on DXA before the start of this study is -1.0SD and more of the mean value of young adult females (YAM), and the BMD for the femoral neck is -1.0SD and more of YAM
5) Patients without lumbar vertebral or femoral fracture
6) Those with an ECOG PS of 0-2
7) Those with adequate organ functions (laboratory data within 4 weeks before case registration)
-Leukocyte count, 3,000/mm3 and more or
Neutrophil count, 1,500/mm3 and more
-AST, ALT, 1.5 and less fold of the upper limit of the institutional reference range
-Serum creatinine, 1.5 and less fold of the upper limit of the institutional reference range
8) Case registration should be performed before the following point:
-Twelve weeks after the completion of surgery or postoperative chemotherapy
(The completion of chemotherapy refers to the completion of the final course, involving the recovery phase.)
9) Patients with an interval of 4 and less weeks after the discontinuation of therapy with bisphosphonates (oral preparations), estrogen preparations, raloxifene, calcitonin preparations, vitamin K preparations, active vitamin D preparations, or ipriflavone preparations, which influence bones
10) Those from whom written informed consent regarding study participation was obtained
Key exclusion criteria
1) Patients in whom distant metastasis was confirmed clinically or using imaging procedures at the time of case registration
2) Those with bilateral breast cancer
3) Those for whom postoperative hormonal therapy was started before consenting to study participation
4) Those who received endocrine therapy within 52 weeks before consenting to study participation
5) Those to whom bisphosphonate preparations were intravenously administered within 52 weeks before consenting to study participation
6) Those with the following diseases that may affect DXA
-Severe scoliosis, immobility, hyperostosis or osteosclerosis of the lumbar vertebrae, calcification of the abdominal aorta, and vertebral disease
7) Those with a history of malignant tumors other than breast cancer within 260 weeks before consenting to study participation
8) Those with dental diseases, such as infectious diseases of the teeth or jaw and tooth trauma. Those for whom tooth or jaw surgery is scheduled within 6 weeks after consenting to study participation (tooth extraction, implantation)
9) Others who are considered to be ineligible by the chief investigator
Target sample size
160
Research contact person
Name of lead principal investigator
| 1st name | Koichi |
| Middle name | |
| Last name | Sakaguchi |
Organization
Kyoto Prefectural University of Medicine
Division name
Department of Endocrine and Breast Surgery
Zip code
602-8566
Address
465 kajii-cho Kawaramachi Hirokoji kamigyo-ku Kyoto Japan
TEL
075-251-5534
ksak@koto.kpu-m.ac.jp
Public contact
Name of contact person
| 1st name | Midori |
| Middle name | |
| Last name | Morita |
Organization
Kyoto Prefectural University of Medicine
Division name
Department of Endocrine and Breast Surgery
Zip code
6028566
Address
465 kajii-cho Kawaramachi Hirokoji kamigyo-ku Kyoto Japan
TEL
075-251-5534
Homepage URL
midori@koto.kpu-m.ac.jp
Sponsor or person
Institute
Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine
Institute
Department
Personal name
Funding Source
Organization
Japanese Breast Cancer Society
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Other related organizations
Co-sponsor
CTREC in Kyoto Prefectural University of Medicine
Name of secondary funder(s)
IRB Contact (For public release)
Organization
same as above
Address
same as above
Tel
0752515111
rinri@koto.kpu-m.ac.jp
Secondary IDs
Secondary IDs
YES
Study ID_1
NCT03324932
Org. issuing International ID_1
Clincal Trials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
京都府立医科大学
東京医科大学
浜松医科大学
呉医療センター
国立病院機構千葉医療センター
横浜市立大学附属市民総合医療センター
東海大学医学部付属病院
弘前大学
赤坂三浦クリニック
北海道がんセンター
神戸大学
獨協医科大学
総合上飯田第一病院
淀川キリスト教病院
秋田大学
神戸海星病院
兵庫県立がんセンター
松下記念病院
市立奈良病院
済生会滋賀県病院
済生会京都府病院
大阪府済生会中津病院
加藤乳腺クリニック
亀岡市立病院
国際医療福祉大学成田病院
Other administrative information
Date of disclosure of the study information
| 2016 | Year | 07 | Month | 01 | Day |
Related information
URL releasing protocol
https://pubmed.ncbi.nlm.nih.gov/31393399/
Publication of results
Partially published
Result
URL related to results and publications
https://sabcs.org/events/
Number of participants that the trial has enrolled
83
Results
Eighty-three enrolled. At 12 months, lumbar spine BMD was +4.6% with denosumab (n=32) vs -3.7% control (n=34); adjusted difference +8.1% (95% CI 6.2-10.1; p<0.01). Fractures within 3 years: 0 vs 1 (p=0.53). Any-grade AEs: 33% vs 32%; no osteonecrosis of the jaw or atypical femoral fractures. No differences in disease-free or overall survival.
Results date posted
| 2025 | Year | 11 | Month | 19 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
| 2025 | Year | 12 | Month | 10 | Day |
Baseline Characteristics
Multicenter, open-label, randomized controlled trial.
Inclusion Criteria: Postmenopausal women with HR+, stage I-IIIA breast cancer, receiving postoperative adjuvant endocrine therapy.
BMD, defined as: L1-L4 T-score >= -1.0 and Femoral neck T-score >= -1.0.
Participant flow
Patients were randomized 1:1 to endocrine therapy alone or plus denosumab 60 mg every 6 months. Primary endpoint: percent change in lumbar spine (L1-L4) BMD at 12 months. Secondary endpoints: femoral neck BMD, fractures, adverse events (AEs), disease-free and overall survival.
Adverse events
The number of treatment-related adverse events was similar in each group: 13 in the denosumab group, and 12 in the placebo group.
No cases of osteonecrosis of the jaw and atypical femoral fracture were reported.
Outcome measures
The primary endpoint was met with high statistical significance (p<0.001). Denosumab therapy resulted in a significant preservation and gain of BMD compared to the control group. The Denosumab group demonstrated a continuous increase in BMD. Denosumab benefit was consistent across all subgroups. No differences in disease-free or overall survival
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
No longer recruiting
Date of protocol fixation
| 2016 | Year | 12 | Month | 20 | Day |
Date of IRB
| 2016 | Year | 10 | Month | 04 | Day |
Anticipated trial start date
| 2017 | Year | 09 | Month | 25 | Day |
Last follow-up date
| 2023 | Year | 10 | Month | 31 | Day |
Date of closure to data entry
| 2024 | Year | 11 | Month | 16 | Day |
Date trial data considered complete
| 2024 | Year | 11 | Month | 25 | Day |
Date analysis concluded
| 2025 | Year | 02 | Month | 17 | Day |
Other
Other related information
Management information
Registered date
| 2016 | Year | 05 | Month | 10 | Day |
Last modified on
| 2025 | Year | 11 | Month | 19 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024427
