Efficacy of Denosumab on Normal BMD in Women Receiving Adjuvant Aromatase Inhibitors for Early Breast Cancer

Kyoto Prefectural University of Medicine

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Denosumab Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT03324932

CQARD-EBS-160402

jRCTs051180211 (Registry Identifier)

Details and patient eligibility

About

This multicenter, randomized, comparative study will evaluate the efficacy of denosumab to prevent the adjuvant therapy of aromatase inhibitors-induced loss of bone mineral density (BMD) in breast cancer patients with normal BMD. Investigators will compare the inhibitory effects of denosumab on bone loss between participants with normal BMD to whom Letrozole or Arimidex will be administered as postoperative endocrine therapy for stage I-IIIA postmenopausal hormone-sensitive breast cancer and controls.

Full description

Normal BMD means T score is ≥-1.0 for the lumbar vertebrae (L1-L4) and/or the femoral neck.

Enrollment: 160 estimated patients

Sex: Female

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients must meet all of the following items at the time of case registration:

1. Patients with infiltrative breast cancer, aged ≥20 years, meeting the following definitions:

   • Those pathologically diagnosed with stage I, II, or IIIA breast cancer (Cancer Management Regulations, 11th version)
   • Those who underwent appropriate surgery, such as mastectomy and breast-preserving surgery

2. Estrogen receptor (ER)- or progesterone receptor (PgR)-positive patients on immunohistochemical (IHC) staining

3. Females meeting one of the following criteria for menopause:

   • Those, aged ≥55 years, without menstruation
   • Those, aged <55 years, with amenorrhea for ≥12 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 of the mean value of young adult females (YAM), and the BMD for the femoral neck is ≥-1.0SD 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 or Neutrophil count, ≥1,500/mm3
   • AST, ALT, ≤1.5-fold of the upper limit of the institutional reference range
   • Serum creatinine, ≤1.5-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 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

Exclusion criteria

Whether each patient meets any of the following items must be checked on case registration:

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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160 participants in 1 patient group

AI+denosumab VS only AI

Other group

Description:

We compare AI intake+denosumab injection and AI intake only in patients with normal BMD to whom Letrozole or Arimidex will be administered as postoperative endocrine therapy, and we assess the efficacy of denosumab injection on bone loss by adjuvant endocrine therapy.

Treatment:

Drug: Denosumab Injection