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

NCT ID: NCT03324932

Last Updated: 2023-10-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-25
• Study Completion Date: 2027-12-31

Brief Summary

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.

Detailed Description

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

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

AI+denosumab VS only AI

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.

Group Type: OTHER

Denosumab Injection

Intervention Type: DRUG

AI intake + denosumab injection per 6 months VS only AI intake

Interventions

Denosumab Injection

AI intake + denosumab injection per 6 months VS only AI intake

Intervention Type: DRUG

Other Intervention Names

pralia

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Kyoto Prefectural University of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Hisako Ono, MD, PhD

Principal Invetstigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hisako Ono, PhD

Role: STUDY_DIRECTOR

Kyoto Prefectural University of Medicine

Tetsuya Taguchi, PhD

Role: PRINCIPAL_INVESTIGATOR

Kyoto Prefectural University of Medicine

Locations

Hisako Ono

Kyoto, , Japan

Countries

Japan

References

Nakatsukasa K, Koyama H, Ouchi Y, Ono H, Sakaguchi K, Matsuda T, Kato M, Ishikawa T, Yamada K, Yoshimura M, Koizumi K, Sakurai T, Shigematsu H, Takahashi S, Taira S, Suzuki M, Narui K, Niikura N, Hasegawa Y, Miura D, Konishi E, Taguchi T; Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results. Breast Cancer. 2019 Jan;26(1):106-112. doi: 10.1007/s12282-018-0896-y. Epub 2018 Jul 27.

Reference Type: BACKGROUND

PMID: 30054855 (View on PubMed)

Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

Reference Type: DERIVED

PMID: 38979716 (View on PubMed)

Sakaguchi K, Ono H, Nakatsukasa K, Ishikawa T, Hasegawa Y, Takahashi M, Niikura N, Koizumi K, Sakurai T, Shigematsu H, Takahashi S, Taira S, Suzuki M, Narui K, Miura D, Yamada K, Yoshimura M, Shioya H, Konishi E, Isao Y, Imai K, Fujikawa K, Taguchi T; Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. Efficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer. Medicine (Baltimore). 2019 Aug;98(32):e16770. doi: 10.1097/MD.0000000000016770.

Reference Type: DERIVED

PMID: 31393399 (View on PubMed)

Other Identifiers

jRCTs051180211

Identifier Type: REGISTRY

Identifier Source: secondary_id

CQARD-EBS-160402

Identifier Type: -

Identifier Source: org_study_id