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

NCT03324932 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CQARD-EBS-160402jRCTs051180211
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

bone health; hormone-sensitive breast cancer; postmenopausal; aromatase inhibitor; bone mineral density

Outcome Measures

Primary Outcomes (1)

• percentage change in the bone mineral density (BMD) for the lumbar vertebrae (L1-L4) on dual-energy X-ray absorptiometry (DXA)

  The change is a value obtained by subtracting 1 from the BMD after 12 months/baseline BMD is expressed as a percentage

  12 months after the start of this study

Secondary Outcomes (9)

• percentage change in the BMD for the lumbar vertebrae (L1-L4) on DXA

  after 2, 3, 4, and 5 years

• percentage change in the BMD for the femoral neck

  after 12 months and 2/3/4/5 years

• percentage change in the BMD for the radius (an ultrasonic bone densimeter is used)institutions in which ultrasonic bone densimeters are used)

  after 2 and 4 weeks, every 4 weeks thereafter (for 2 years after registration)(only

• Changes in Ca and bone metabolism markers

  after 24 weeks

• Appearance rate of morbid fracture in all participants

  up to 3 years

Study Arms (1)

AI+denosumab VS only AI

OTHER

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.

Drug: Denosumab Injection

Interventions

Denosumab Injection DRUG

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

Also known as: pralia

AI+denosumab VS only AI

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following items at the time of case registration:
• 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
• Estrogen receptor (ER)- or progesterone receptor (PgR)-positive patients on immunohistochemical (IHC) staining
• 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
• 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
• Patients without lumbar vertebral or femoral fracture
• Those with an ECOG PS of 0-2
• 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

You may not qualify if:

• Whether each patient meets any of the following items must be checked on case registration:
• Patients in whom distant metastasis was confirmed clinically or using imaging procedures at the time of case registration
• Those with bilateral breast cancer
• Those for whom postoperative hormonal therapy was started before consenting to study participation
• Those who received endocrine therapy within 52 weeks before consenting to study participation
• Those to whom bisphosphonate preparations were intravenously administered within 52 weeks before consenting to study participation
• 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
• Those with a history of malignant tumors other than breast cancer within 260 weeks before consenting to study participation
• 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)
• Others who are considered to be ineligible by the chief investigator

Sponsors & Collaborators

• Kyoto Prefectural University of Medicine: lead

Study Sites (1)

Hisako Ono

Kyoto, 6028566, Japan

Location

Related Publications (3)

• 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.

  PMID: 30054855 BACKGROUND

• 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.

  PMID: 38979716 DERIVED

• 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.

  PMID: 31393399 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hisako Ono, PhD

  Kyoto Prefectural University of Medicine

  STUDY DIRECTOR

• Tetsuya Taguchi, PhD

  Kyoto Prefectural University of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Invetstigator

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: October 30, 2017
• Study Start: September 25, 2017
• Primary Completion: December 1, 2023
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 6, 2023

Record last verified: 2023-10

Locations

JP (1)