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Breast CancerPhase 3NCT03324932

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

A Phase 3 study testing Denosumab Injection in people with Breast Cancer, run by Kyoto Prefectural University of Medicine at 1 site in Japan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Denosumab Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
1 siteJapan
Study dates
25 Sep 2017to Dec 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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
  • Serum creatinine, ≤1.5-fold of the upper limit of the institutional reference range
  • 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.)
  • 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
  • Those from whom written informed consent regarding study participation was obtained

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • Hisako Ono

    Kyoto, 6028566

Other trials in Japan

About this study

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)

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.

Read the detailed description

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

Conditions
Breast Cancer
Being tested
Denosumab Injection
Keywords
bone health, hormone-sensitive breast cancer, postmenopausal, aromatase inhibitor, bone mineral density
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Denosumab InjectionDrug

    Also called pralia

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

Study groups in NCT03324932
Study groupRoleWhat they receive
AI+denosumab VS only AIOtherWe 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.
Receives: Drug: Denosumab Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 months after the start of this study

Secondary outcomes (9)

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

    percentage change in the BMD for the femoral neck: After 2/3/4/5 years

    Measured: after 2, 3, 4, and 5 years

  2. percentage change in the BMD for the femoral neck

    percentage change in the BMD for the femoral neck: After 12 months and 2/3/4/5 years

    Measured: 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)

    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)

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

  4. Changes in Ca and bone metabolism markers

    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

    Measured: after 24 weeks

  5. Appearance rate of morbid fracture in all participants

    Appearance rate of morbid fracture up to 3 years in all participants. Morbid fractures include all types of fractures.

    Measured: up to 3 years

  6. Disease-free survival

    Disease-free survival at the end of the study

    Measured: at least 5 year

  7. Overall survival

    Overall survival at the end of the study

    Measured: at least 5 year

  8. Appearance of adverse events

    Appearance rate of adverse events (such as hypocalcemia and necrosis of the jaw)

    Measured: at least 5 year

  9. Quality of life (QOL)

    Quality of life(QOL), Japanese version Euro-Qol (EQ-5D-5L) evaluated by questionnaire at every 6 months

    Measured: after 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2017
  2. Study start25 Sep 2017
  3. Primary completionDec 2023 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03324932
Sponsor's protocol ID
CQARD-EBS-160402
Other IDs
jRCTs051180211
Status last verified
Oct 2023
First submitted
21 Sep 2017
Last updated
6 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 30054855

  • 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.

    PubMed 38979716

  • 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.

    PubMed 31393399

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Denosumab Injection in people with Breast Cancer, run by Kyoto Prefectural University of Medicine at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03324932, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.

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