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

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ClinicalTrials.gov Identifier: NCT03324932
Recruitment Status : Recruiting
First Posted : October 30, 2017
Last Update Posted : October 31, 2017
Sponsor:
Information provided by (Responsible Party):
Hisako Ono, MD, Kyoto Prefectural University of Medicine

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Denosumab Injection Phase 3

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multicenter, Randomized, Comparative Study Regarding the Efficacy of Denosumab on Normal Bone Mineral Density in Women Receiving Adjuvant Aromatase Inhibitors for Early Breast Cancer (ENDEAVOR Trial)
Actual Study Start Date : September 25, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Denosumab
U.S. FDA Resources

Arm Intervention/treatment
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.
Drug: Denosumab Injection
AI intake + denosumab injection per 6 months VS only AI intake
Other Name: pralia



Primary Outcome Measures :
  1. percentage change in the bone mineral density (BMD) for the lumbar vertebrae (L1-L4) on dual-energy X-ray absorptiometry (DXA) [ Time Frame: 12 months after the start of this study ]
    The change is a value obtained by subtracting 1 from the BMD after 12 months/baseline BMD is expressed as a percentage


Secondary Outcome Measures :
  1. percentage change in the BMD for the lumbar vertebrae (L1-L4) on DXA [ Time Frame: after 2, 3, 4, and 5 years ]
    percentage change in the BMD for the femoral neck: After 2/3/4/5 years

  2. percentage change in the BMD for the femoral neck [ Time Frame: after 12 months and 2/3/4/5 years ]
    percentage change in the BMD for the femoral neck: After 12 months and 2/3/4/5 years

  3. percentage change in the BMD for the radius (an ultrasonic bone densimeter is used)institutions in which ultrasonic bone densimeters are used) [ Time Frame: after 2 and 4 weeks, every 4 weeks thereafter (for 2 years after registration)(only ]
    percentage 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 [ Time Frame: after 24 weeks ]
    Changes in Ca (mg/dL corrected by albumin level) and bone metabolism markers such as TRAP5b, bone-specific alkaline phosphatase (BSAP), blood pentosidine) by blood sampling at every 6 months

  5. Appearance rate of morbid fracture in all participants [ Time Frame: up to 3 years ]
    Appearance rate of morbid fracture up to 3 years in all participants. Morbid fractures include all types of fractures.

  6. Disease-free survival [ Time Frame: at least 5 year ]
    Disease-free survival at the end of the study

  7. Overall survival [ Time Frame: at least 5 year ]
    Overall survival at the end of the study

  8. Appearance of adverse events [ Time Frame: at least 5 year ]
    Appearance rate of adverse events (such as hypocalcemia and necrosis of the jaw)

  9. Quality of life (QOL) [ Time Frame: after 24 weeks ]
    Quality of life(QOL), Japanese version Euro-Qol (EQ-5D-5L) evaluated by questionnaire at every 6 months



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Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03324932


Contacts
Contact: Hisako Ono, MD 0752515534 ext 81 hisako-o@koto.kpu-m.ac.jp
Contact: Tetsuya Taguchi, PhD 0752515534 ext 81 ttaguchi@koto.kpu-m.ac.jp

Locations
Japan
Hisako Ono Recruiting
Kyoto, Japan, 6028566
Contact: Hisako Ono, MD    0752515534    hisako-o@koto.kpu-m.ac.jp   
Contact: Tetsuya taguchi, PhD    0752515534    ttaguchi@koto.kpu-m.ac.jp   
Sub-Investigator: Hisako Ono, MD         
Sponsors and Collaborators
Kyoto Prefectural University of Medicine
Investigators
Study Director: Hisako Ono, MD Kyoto Prefectural University of Medicine
Principal Investigator: Tetsuya Taguchi, PhD Kyoto Prefectural University of Medicine

Responsible Party: Hisako Ono, MD, Principal Invetstigator, Kyoto Prefectural University of Medicine
ClinicalTrials.gov Identifier: NCT03324932     History of Changes
Other Study ID Numbers: CQARD-EBS-160402
First Posted: October 30, 2017    Key Record Dates
Last Update Posted: October 31, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Hisako Ono, MD, Kyoto Prefectural University of Medicine:
bone health
hormone-sensitive breast cancer
postmenopausal
aromatase inhibitor
bone mineral density

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Denosumab
Aromatase Inhibitors
Bone Density Conservation Agents
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists