CClinicalTrials.gg
Sign In
CompletedNCT00556374Updated Jul 27, 2023Results posted

Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy

A Phase 3 interventional study of Placebo and Denosumab in Breast Cancer, sponsored by Amgen. Completed at 47 sites in 2 countries. Open to female participants aged 45 Years to 100 Years. Per ClinicalTrials.gov, last updated 2023-07-27.

Sponsored by Amgen · Phase 3, Interventional, and Supportive care

From the registry’s dates

  • Registered 10 months after the study started (first participant enrolled Dec 2006, registered Nov 2007).
Phase
Phase 3
Study type
Interventional
Enrollment
3,420
Allocation
Randomized
Ages
45 Years to 100 Years
Sex
Female
01

Study summary

The purpose of this study is to determine whether denosumab compared to placebo, will reduce the rate of first clinical fracture in women with non-metastatic breast cancer receiving (non-steroidal) aromatase inhibitor therapy.

Read the detailed description

Participants will remain on treatment until the required number of events (where an event is defined as first clinical fracture) is reached and all participants have had the opportunity to receive a minimum of at least 2 doses of study drug, whichever occurs later. The primary analysis data cut-off date (PADCD) is defined as the time at which the required number of events is reached and all participants have had the opportunity to receive at least 2 doses of study drug. When the PADCD is reached, all participants will discontinue study drug.

Following the study PADCD, participants will be followed every 12 months starting from their last study visit until a maximum of 66 months after PADCD.

After approval of Amendment 4, willing and eligible participants randomized to placebo during the double-blind phase may participate in an open-label phase (OLP) and receive denosumab 60 mg Q6M for up to 36 months (maximum of 7 doses).

After approval of Amendment 6 in 2019 a zoledronic acid (ZA) substudy was added to the protocol. Willing and eligible participants who participated in the OLP of the study and completed open-label denosumab may opt in to this ZA substudy and either receive a single dose of ZA (Therapy Arm), or be managed according to the current standard of care for this patient population (Control Arm).

02

Conditions studied

  • Breast Cancer

Browse trials for

Keywords

  • confirmed adenocarcinoma
  • non-metastatic breast cancer
  • estrogen receptor positive
  • progesterone receptor positive
  • non-steroidal aromatase
  • aromatase inhibitor therapy
  • postmenopausal woman
  • adjuvant chemotherapy
  • neoadjuvant chemotherapy
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 3,420 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.

Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
45 Years to 100 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Histologically or cytologically confirmed adenocarcinoma of the breast;
  • Female subjects with non-metastatic disease who are estrogen receptor (ER) and/or progesterone receptor (PR) positive, and who have completed their treatment pathway;
  • Subjects who are currently on, or will initiate an approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting;

  • Postmenopausal woman, defined as a woman fulfilling any one of the following criteria:

    • Having undergone a bilateral oophorectomy;
    • Age ≥ 60 years;
    • Aged \< 60 years meeting the following requirements:
  • Follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range;
  • A negative pregnancy test within 7 days prior to randomization. Subjects who have undergone a hysterectomy do not require a pregnancy test.
  • More criteria may apply.

Exclusion criteria

Exclusion Criteria for Double Blinded Phase:

  • Aromatase inhibitor therapy for more than 24 months;
  • Prior or concurrent treatment with Selective Estrogen Receptor Modulators (eg, tamoxifen);
  • Evidence of metastatic disease;
  • Current or prior intravenous (IV) bisphosphonate administration;
  • Oral bisphosphonate treatment greater than or equal to 3 years continuously OR greater than 3 months but less than 3 years unless there was a washout period of at least 1 year prior to randomization OR any use during the 3-month period prior to randomization;
  • Prior administration of denosumab;
  • Known liver or renal deficiency;
  • Recurrence of the primary malignancy (e.g., during the allowed interval of pretreatment with aromatase inhibitor);
  • Diagnosis of any second non-breast malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri;
  • Any kind of disorder that compromises the ability to give written informed consent and/or comply with study procedures.

Inclusion Criteria to Receive Open-label Phase Denosumab:

  • Obtain signed and dated written informed consent prior to performing any study-specific procedure;
  • Subjects currently taking an approved non-steroidal AIT (eg, anastrazole) or who have completed or discontinued AIT within 12 months prior to participation in the OLP;
  • Randomized to placebo arm during the double-blind phase (as determined by unblinding procedures);

Exclusion Criteria to Receive Open-label Phase Denosumab:

  • Current or prior IV bisphosphonate administration;

  • Subjects meeting the following criteria for oral bisphosphonate treatment:

    • Greater than or equal to 3 years continuously,
    • Greater than 3 months but less than 3 years unless subject has had a washout period of at least 1 year prior to participation in the OLP,
    • Any use during the 3-month period prior to participation in the OLP;
  • Prior or concurrent treatment with SERMs (eg, tamoxifen);
  • Subjects who ended treatment with investigational product (IP) prematurely in the double-blind phase; Treatment with commercial denosumab (Prolia or Xgeva) prior to participation in the OLP.

Eligibility for ZA substudy Inclusion Criteria

  • Obtain signed and dated written informed consent prior to performing any substudy-specific procedure
  • Subjects that received OLP denosumab and completed OLP treatment
  • Last OLP denosumab administration no longer than 9 months ago Exclusion Criteria
  • Current or prior ZA administration.
  • Subjects who ended treatment with investigational product (IP) prematurely in the double-blind phase and OL phase
  • Known sensitivity or intolerance to any of the products to be administered during the substudy (eg, ZA, calcium or vitamin D)

  • Known history of any of the following conditions either by subject self report or chart review

    • Paget's disease (bone), Cushing's disease, hyperprolactinemia or other active metabolic bone disease
    • Known history of hypocalcemia
    • Major surgery, or significant traumatic injury occurring within 4 weeks prior to randomization
    • Parathyroid glands in neck surgically removed.
    • Any sections of intestine removed.
    • Known human immunodeficiency virus infection
    • Active infection with hepatitis B or hepatitis C virus

  • Known liver or renal disease as determined by the investigator and indicated by the following criteria:

    • Aspartate aminotransferase ≥ 2.5 x ULN
    • Alanine transaminase ≥ 2.5 x ULN
    • Serum creatinine ≥ 2 x ULN
    • Creatine clearance \< 35ml/min Subjects that are pregnant or breastfeeding
    • All subjects with reproductive potential must have a negative pregnancy test within 7 days before randomization
  • Subjects who are osteoporotic in baseline BMD
05

Study design

Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
3,420 participants (actual)

Study arms

  • Experimental
    Denosumab

    Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

    Biological: Denosumab · Drug: Non-steroidal aromatase inhibitor therapy

  • Placebo comparator
    Placebo

    Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.

    Drug: Placebo · Drug: Non-steroidal aromatase inhibitor therapy

  • Experimental
    SubStudy: Zoledronic Acid

    Eligible participants who completed the open-label phase could be enrolled into the zoledronic acid substudy and randomized to receive a single 5 mg intravenous dose of zoledronic acid 8 months after the last open-label dose of denosumab.

    Drug: Zoledronic Acid

  • Other
    Substudy: Standard of Care

    Eligible participants who completed the open-label phase could be enrolled into the zoledronic acid substudy and randomized to receive standard of care 8 months after the last open-label dose of denosumab.

    Other: Standard of Care

Interventions

  • DrugPlacebo

    Also known as: Administered as a subcutaneous injection

  • BiologicalDenosumab

    Administered as a subcutaneous injection

    Also known as: Prolia®

  • DrugNon-steroidal aromatase inhibitor therapy

    An approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting

  • DrugZoledronic Acid

    5 mg zoledronic acid administered at a constant infusion rate

    Also known as: Reclast, Zometa

  • OtherStandard of Care

    Standard of care (SoC) as recommended by the treating physician, depending on individual factors such as bone density, lifestyle recommendations by the Investigator such as diet, physical activities and sun exposure, as well as local treatment standards.

06

What researchers measure

Primary outcomes

  1. Time to First Clinical Fracture

    The time to first on-study clinical fracture was defined as the number of days from randomization to the date of the x-ray confirming the clinical fracture. A clinical fracture is any clinically evident fracture with associated symptoms and confirmed by x-ray. Participants who died or withdrew without experiencing a clinical fracture were censored at the date of last contact or study termination whichever was earlier.

    Time frame: From randomization until the primary analysis cut-off date of 26 March 2014; maximum time on main study at the cut-off was 87 months

Secondary outcomes

  1. Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites

    Bone mineral density was assessed by dual x-ray absorptiometry.

    Time frame: Baseline and Month 36

  2. Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites

    Bone mineral density was assessed by dual x-ray absorptiometry.

    Time frame: Baseline and Month 36

  3. Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites

    Bone mineral density was assessed by dual x-ray absorptiometry.

    Time frame: Baseline and Month 36

  4. Number of Participants With New Vertebral Fractures

    Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height. A new vertebral fracture was defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays.

    Time frame: 36 months

  5. Number of Participants With New or Worsening Vertebral Fractures

    Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height. A new vertebral fracture was defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays. Worsening of pre-existing fractures was defined as an increase in fracture severity of at least 1 grade on the semiquantitative scale.

    Time frame: 36 months

  6. Disease-free Survival (DFS)

    DFS was defined as the time interval from the randomization date to the date of first evidence of local or distant metastases, contra-lateral breast cancer, secondary carcinoma, or death from any cause (whichever occurred first). Participants last known to be alive, who did not experience recurrence of disease, were censored at their last contact date or at the data cut-off date whichever came first.

    Time frame: From randomization until the DFS data cut-off date of 15 September 2015; maximum time on main study at the cut-off was 102 months

  7. Bone Metastases-free Survival (BMFS)

    BMFS was defined as the time interval from randomization to first occurrence of bone metastasis or death from any cause, whichever comes first. Participants last known to be alive, who did not experience bone metastasis, were censored at their last assessment (i.e., bone scan) date or at the last contact date, whichever comes first.

    Time frame: From randomization until end of main study, maximum time on main study was 152 months

  8. Overall Survival (OS)

    OS was defined as the time from randomization to death from any cause.

    Time frame: Randomization until end of main study, maximum duration of main study was 152 months

07

Results

Posted Nov 6, 2015

Participant flow

Participants were enrolled at 58 centers in Austria and Sweden from December 2006 to August 2020. Data collected during the exploratory ZA substudy were not used for the final analysis of the main study.

Participant flow — Overall Study
MilestonePlaceboDenosumab
Started17091711
Received study drug in the double-blind phase16991700
Continued into the open-label phase2683
Safety analysis set16901709
Completed12421362
Not completed467349
Withdrew: Withdrawal by subject235205
Withdrew: Death158127
Withdrew: Lost to follow-up2417
Withdrew: Continuing into zoledronic acid substudy500

Outcome measures

PrimaryTime to First Clinical Fracture

The time to first on-study clinical fracture was defined as the number of days from randomization to the date of the x-ray confirming the clinical fracture. A clinical fracture is any clinically evident fracture with associated symptoms and confirmed by x-ray. Participants who died or withdrew without experiencing a clinical fracture were censored at the date of last contact or study termination whichever was earlier.

Time frame:
From randomization until the primary analysis cut-off date of 26 March 2014; maximum time on main study at the cut-off was 87 months
Reported as:
Median · Days
Time to First Clinical Fracture
DaysPlaceboDenosumab
Time to First Clinical FractureNA (NA to NA)NA (NA to NA)
Statistical analysis
  • Placebo vs Denosumab · Cox Proportional Hazards Model · p = <0.0001 · Hazard ratio (hr): 0.504 · 95% CI 0.39 to 0.65From the Cox proportional hazard model with treatment as the independent variable and stratified by randomization strata. A hazard ratio \< 1.0 indicates a lower average event rate and a longer fracture-free time for denosumab relative to placebo.
SecondaryPercent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites

Bone mineral density was assessed by dual x-ray absorptiometry.

Time frame:
Baseline and Month 36
Reported as:
Least squares mean · Percent Change in BMD
Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites
Percent Change in BMDPlaceboDenosumab
Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites-2.75 (-3.44 to -2.07)7.27 (6.56 to 7.98)
Statistical analysis
  • Placebo vs Denosumab · ANCOVA · p = <0.0001 (The Hochberg procedure was used to control for multiplicity.) · Difference from placebo: 10.02 · 95% CI 9.04 to 11.01Model includes treatment group as the independent variable and adjusted for baseline value and the randomization stratification factors.
SecondaryPercent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites

Bone mineral density was assessed by dual x-ray absorptiometry.

Time frame:
Baseline and Month 36
Reported as:
Least squares mean · Percent Change in BMD
Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites
Percent Change in BMDPlaceboDenosumab
Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites-3.32 (-4.06 to -2.58)4.60 (3.85 to 5.35)
Statistical analysis
  • Placebo vs Denosumab · ANCOVA · p = <0.0001 (The Hochberg procedure was used to control for multiplicity.) · Difference from placebo: 7.92 · 95% CI 6.87 to 8.97Model includes treatment group as the independent variable and adjusted for baseline value and the randomization stratification factors.
SecondaryPercent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites

Bone mineral density was assessed by dual x-ray absorptiometry.

Time frame:
Baseline and Month 36
Reported as:
Least squares mean · Percent Change in BMD
Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites
Percent Change in BMDPlaceboDenosumab
Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites-3.10 (-3.72 to -2.48)3.41 (2.78 to 4.04)
Statistical analysis
  • Placebo vs Denosumab · ANCOVA · p = <0.0001 (The Hochberg procedure was used to control for multiplicity.) · Difference from placebo: 6.51 · 95% CI 5.62 to 7.39Model includes treatment group as the independent variable and adjusted for baseline value and the randomization stratification factors.
SecondaryNumber of Participants With New Vertebral Fractures

Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height. A new vertebral fracture was defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays.

Time frame:
36 months
Reported as:
Count of participants · Participants
Number of Participants With New Vertebral Fractures
ParticipantsPlaceboDenosumab
Number of Participants With New Vertebral Fractures4927
Statistical analysis
  • Placebo vs Denosumab · Regression, Logistic · p = 0.0088 · Odds ratio (or): 0.53 · 95% CI 0.33 to 0.85Values \< 1 for odds ratio favor denosumab.
SecondaryNumber of Participants With New or Worsening Vertebral Fractures

Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height. A new vertebral fracture was defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays. Worsening of pre-existing fractures was defined as an increase in fracture severity of at least 1 grade on the semiquantitative scale.

Time frame:
36 months
Reported as:
Count of participants · Participants
Number of Participants With New or Worsening Vertebral Fractures
ParticipantsPlaceboDenosumab
Number of Participants With New or Worsening Vertebral Fractures5531
Statistical analysis
  • Placebo vs Denosumab · Regression, Logistic · p = 0.0070 · Odds ratio (or): 0.54 · 95% CI 0.34 to 0.84Values \< 1 for odds ratio favor denosumab.
SecondaryDisease-free Survival (DFS)

DFS was defined as the time interval from the randomization date to the date of first evidence of local or distant metastases, contra-lateral breast cancer, secondary carcinoma, or death from any cause (whichever occurred first). Participants last known to be alive, who did not experience recurrence of disease, were censored at their last contact date or at the data cut-off date whichever came first.

Time frame:
From randomization until the DFS data cut-off date of 15 September 2015; maximum time on main study at the cut-off was 102 months
Reported as:
Median · Days
Disease-free Survival (DFS)
DaysPlaceboDenosumab
Disease-free Survival (DFS)NA (NA to NA)NA (NA to NA)
Statistical analysis
  • Placebo vs Denosumab · Cox Proportional Hazards Model · p = 0.0515 · Hazard ratio (hr): 0.816 · 95% CI 0.66 to 1.00From the Cox Proportional hazards model with treatment fitted as a covariate and stratified by randomization strata. A hazard ratio \< 1.0 indicates a lower average event rate and a longer disease-free time for denosumab relative to placebo.
SecondaryBone Metastases-free Survival (BMFS)

BMFS was defined as the time interval from randomization to first occurrence of bone metastasis or death from any cause, whichever comes first. Participants last known to be alive, who did not experience bone metastasis, were censored at their last assessment (i.e., bone scan) date or at the last contact date, whichever comes first.

Time frame:
From randomization until end of main study, maximum time on main study was 152 months
Reported as:
Median · Days
Bone Metastases-free Survival (BMFS)
DaysPlaceboDenosumab
Bone Metastases-free Survival (BMFS)NA (NA to NA)NA (NA to NA)
Statistical analysis
  • Placebo vs Denosumab · Hazard ratio (hr): 0.808 · 95% CI 0.654 to 0.997A hazard ratio \< 1.0 indicates a lower average event rate and a longer bone metastases-free time for denosumab relative to placebo.
SecondaryOverall Survival (OS)

OS was defined as the time from randomization to death from any cause.

Time frame:
Randomization until end of main study, maximum duration of main study was 152 months
Reported as:
Median · Days
Overall Survival (OS)
DaysPlaceboDenosumab
Overall Survival (OS)NA (NA to NA)NA (NA to NA)
Statistical analysis
  • Placebo vs Denosumab · Hazard ratio (hr): 0.802 · 95% CI 0.635 to 1.013A hazard ratio \< 1.0 indicates a lower average event rate and a longer overall survival time for denosumab relative to placebo.

Adverse events

Collected over Double-blind (DB) phase: from 1st dose of study drug to 30 days after last dose; Open-label (OL) phase: from 1st dose of OL study drug to 30 days after last dose. Median duration of treatment in DB phase: Placebo 35.4 months and denosumab 35.5 months. Median duration of treatment in OL phase: 37 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Double-blind Phase: Placebo—515/1,690 (30.5%)838/1,690 (49.6%)
Double-blind Phase: Denosumab—521/1,709 (30.5%)882/1,709 (51.6%)
Open-label Phase: Placebo/Denosumab—40/245 (16.3%)0/245 (0%)
Open-label Phase: Denosumab/Denosumab—0/1 (0%)0/1 (0%)
Most frequent serious events
Showing 10 of 618
Most frequent serious events
EventDouble-blind Phase: PlaceboDouble-blind Phase: DenosumabOpen-label Phase: Placebo/DenosumabOpen-label Phase: Denosumab/Denosumab
OsteoarthritisMusculoskeletal and connective tissue disorders59/169062/17092/2450/1
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders15/169014/17095/2450/1
CataractEye disorders28/169016/17092/2450/1
Meniscus injuryInjury, poisoning and procedural complications24/169023/17090/2450/1
GoitreEndocrine disorders12/169021/17091/2450/1
Atrial fibrillationCardiac disorders11/169014/17093/2450/1
DiverticulitisInfections and infestations9/16909/17093/2450/1
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/16901/17093/2450/1
ErysipelasInfections and infestations10/169015/17091/2450/1
Hypertensive crisisVascular disorders14/169010/17091/2450/1
Most frequent other events
Most frequent other events
EventDouble-blind Phase: PlaceboDouble-blind Phase: DenosumabOpen-label Phase: Placebo/DenosumabOpen-label Phase: Denosumab/Denosumab
ArthralgiaMusculoskeletal and connective tissue disorders446/1690441/17090/2450/1
Hot flushVascular disorders234/1690270/17090/2450/1
Back painMusculoskeletal and connective tissue disorders146/1690151/17090/2450/1
Bone painMusculoskeletal and connective tissue disorders111/1690139/17090/2450/1
HypertensionVascular disorders94/1690111/17090/2450/1
FatigueGeneral disorders100/1690109/17090/2450/1
Pain in extremityMusculoskeletal and connective tissue disorders85/1690107/17090/2450/1
OsteoarthritisMusculoskeletal and connective tissue disorders61/169089/17090/2450/1
Spinal painMusculoskeletal and connective tissue disorders73/169089/17090/2450/1
Scar painSkin and subcutaneous tissue disorders86/169078/17090/2450/1

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboDenosumabTotal
Mean64.6 ± 8.064.0 ± 7.964.3 ± 8.0
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboDenosumabTotal
Female170917113420
Male000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)PlaceboDenosumabTotal
White/Caucasian170017023402
Asian7512
Hispanic/Latino134
Black/Afro-Caribbean011
Missing101
Stratification Factor: Type of Hospital
Stratification Factor: Type of Hospital(participants)PlaceboDenosumabTotal
Major Academic Center6326331265
Other Center107710782155
Stratification Factor: Prior Aromatase inhibitor Use
Stratification Factor: Prior Aromatase inhibitor Use(Participants)PlaceboDenosumabTotal
No269270539
Yes144014412881
Stratification Factor: Total Lumbar Spine BMD T-score
Stratification Factor: Total Lumbar Spine BMD T-score(Participants)PlaceboDenosumabTotal
T-score < -1.07757731548
T-score ≥ -1.09349381872
08

Study locations

47 sites
  • Research Site
    Baden, 2500, Austria
  • Research Site
    Braunau, 5280, Austria
  • Research Site
    Dornbirn, 6850, Austria
  • Research Site
    Feldkirch, 6807, Austria
  • Research Site
    Gmunden, 4810, Austria
  • Research Site
    Graz, 8020, Austria
  • Research Site
    Graz, 8036, Austria
  • Research Site
    Güssing, 7540, Austria
  • Research Site
    Hall in Tirol, 6060, Austria
  • Research Site
    Innsbruck, 6020, Austria
  • Research Site
    Klagenfurt, 9026, Austria
  • Research Site
    Krems, 3500, Austria
  • Research Site
    Kufstein, 6330, Austria
  • Research Site
    Leoben, 8700, Austria
  • Research Site
    Lienz, 9900, Austria
  • Research Site
    Linz, 4010, Austria
  • Research Site
    Linz, 4020, Austria
  • Research Site
    Oberpullendorf, 7350, Austria
  • Research Site
    Ried, 4910, Austria
  • Research Site
    Rottenmann, 8786, Austria
  • Research Site
    Salzburg, 5020, Austria
  • Research Site
    Schärding, 4780, Austria
  • Research Site
    St Poelten, 3100, Austria
  • Research Site
    St Veit an der Glan, 9300, Austria
  • Research Site
    St. Poelten, 3100, Austria
  • Research Site
    Steyr, 4400, Austria
  • Research Site
    Villach, 9500, Austria
  • Research Site
    Villach, 9504, Austria
  • Research Site
    Voecklabruck, 4840, Austria
  • Research Site
    Weiz, 8160, Austria
  • Research Site
    Wels, 4600, Austria
  • Research Site
    Wiener Neustadt, 2700, Austria
  • Research Site
    Wien, 1010, Austria
  • Research Site
    Wien, 1020, Austria
  • Research Site
    Wien, 1050, Austria
  • Research Site
    Wien, 1090, Austria
  • Research Site
    Wien, 1130, Austria
  • Research Site
    Wien, 1140, Austria
  • Research Site
    Wien, 1160, Austria
  • Research Site
    Wien, 1180, Austria
  • Research Site
    Wien, 1220, Austria
  • Research Site
    Wolfsberg, 9400, Austria
  • Research Site
    Gävle, 801 87, Sweden
  • Research Site
    Göteborg, Sweden
  • Research Site
    Stockholm, 112 81, Sweden
  • Research Site
    Stockholm, 171 76, Sweden
  • Research Site
    Uppsala, 751 85, Sweden
09

References and documents

Publications

  • Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger E, Bjelic-Radisic V, Artner-Matuschek S, Fitzal F, Marth C, Sevelda P, Mlineritsch B, Steger GG, Manfreda D, Exner R, Egle D, Bergh J, Kainberger F, Talbot S, Warner D, Fesl C, Singer CF; Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Aug 1;386(9992):433-43. doi: 10.1016/S0140-6736(15)60995-3. Epub 2015 May 31. PubMed 26040499 ↗
  • Minichsdorfer C, Fuereder T, Leutner M, Singer CF, Kacerovsky-Strobl S, Egle D, Greil R, Balic M, Fitzal F, Pfeiler G, Frantal S, Bartsch R, Gnant M. Effect of concomitant statin treatment in postmenopausal patients with hormone receptor-positive early-stage breast cancer receiving adjuvant denosumab or placebo: a post hoc analysis of ABCSG-18. ESMO Open. 2022 Apr;7(2):100426. doi: 10.1016/j.esmoop.2022.100426. Epub 2022 Mar 22. PubMed 35334418 ↗
  • Gnant M, Pfeiler G, Steger GG, Egle D, Greil R, Fitzal F, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Jakesz R, Marth C, Sevelda P, Mlineritsch B, Exner R, Fesl C, Frantal S, Singer CF; Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):339-351. doi: 10.1016/S1470-2045(18)30862-3. Epub 2019 Feb 19. PubMed 30795951 ↗

Study documents

  • Study protocol · Jul 15, 2019
  • Statistical analysis plan · Dec 10, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 27, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00556374
Lead sponsor
Amgen
Collaborators
Austrian Breast and Colorectal Cancer Study Group
Responsible party
Sponsor
First posted
Nov 12, 2007
Start date
Dec 18, 2006
Primary completion
Oct 7, 2014
Completion
Jul 26, 2022
Results posted
Nov 6, 2015
Last update
Jul 27, 2023

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Breast Neoplasms→

Other studies from this sponsor

Amgen

Start the discussion