The efficacy of the use of denosumab in the prevention of AI-induced bone loss in postmenopausal patients

JRCT ID: jRCTs051180211

Registered date:27/03/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: breast cancer
• Date of first enrollment: 26/09/2017
• Target sample size: 160
• Study type: Interventional

Intervention(s)

arm control : Measurement of the bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) every 6 months during 5-years oral intake of AI.
arm denosumab : Subcutaneous injection of denosumab, 60 mg/body given and measurement of the BMD by DXA every 6 months during 5-years oral intake of AI.
Repeat until the discontinuance criteria.

Outcome(s)

• Primary Outcome: 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

Secondary Outcome

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)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Female

Include 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

Exclude 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

Related Information

• Primary Sponsor: Sakaguchi Koichi
• Source(s) of Monetary Support: Japanese Breast Cancer Society
• Secondary ID(s): UMIN000022256 NCT03324932