Breast CancerPhase 3NCT00556374

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

A Phase 3 study testing Denosumab, Non-steroidal aromatase inhibitor therapy and Zoledronic Acid in people with Breast Cancer, run by Amgen at 46 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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 more about this study

Who is it for?: Ages 45 to 100 years, women only
Conditions the study is for: Breast Cancer
What is being tested?: Denosumab, Non-steroidal aromatase inhibitor therapy and Zoledronic Acid
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 3,420 participants
Where: 46 sitesin 2 countries
Study dates: 18 Dec 2006to 26 Jul 2022
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 45 to 100 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

Show all 13Show fewer

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.
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);

Who cannot join

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;

Show all 39Show fewer

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.
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

Trial locations and contacts

46 sites in 2 countries.

Country

City, postcode or hospital

46 sites in 2 countries

Austria41 sites

Research Site
Baden, 2500
Research Site
Braunau am Inn, 5280
Research Site
Dornbirn, 6850
Research Site
Feldkirch, 6807
Research Site
Gmunden, 4810
Research Site
Graz, 8020
Research Site
Graz, 8036
Research Site
Guessing, 7540
Research Site
Hall in Tirol, 6060
Research Site
Innsbruck, 6020
Research Site
Klagenfurt, 9026
Research Site
Krems, 3500
Research Site
Kufstein, 6330
Research Site
Leoben, 8700
Research Site
Lienz, 9900
Research Site
Linz, 4010
Research Site
Linz, 4020
Research Site
Oberpullendorf, 7350
Research Site
Ried, 4910
Research Site
Rottenmann, 8786
Research Site
Salzburg, 5020
Research Site
Sankt Pölten, 3100
Research Site
Sankt Veit an der Glan, 9300
Research Site
Schaerding, 4780
Research Site
Steyr, 4400
Research Site
Vienna, 1010
Research Site
Vienna, 1020
Research Site
Vienna, 1050
Research Site
Vienna, 1090
Research Site
Vienna, 1130
Research Site
Vienna, 1140
Research Site
Vienna, 1160
Research Site
Vienna, 1180
Research Site
Vienna, 1220
Research Site
Villach, 9500
Research Site
Villach, 9504
Research Site
Vöcklabruck, 4840
Research Site
Weiz, 8160
Research Site
Wels, 4600
Research Site
Wiener Neustadt, 2700
Research Site
Wolfsberg, 9400

Other trials in Austria

Sweden5 sites

Research Site
Gävle, 801 87
Research Site
Gothenburg
Research Site
Stockholm, 112 81
Research Site
Stockholm, 171 76
Research Site
Uppsala, 751 85

Other trials in Sweden

About this study

Official title: A Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Phase 3 Study to Determine the Treatment Effect of Denosumab in Subjects With Non-Metastatic Breast Cancer Receiving 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).

Conditions: Breast Cancer
Being tested: Placebo, Denosumab, Non-steroidal aromatase inhibitor therapy, Zoledronic Acid, Standard of Care
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
Medical subject headings: Breast Neoplasms

What participants receive

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

PlaceboDrug
Also called Administered as a subcutaneous injection
DenosumabBiological
Also called Prolia®
Administered as a subcutaneous injection
Non-steroidal aromatase inhibitor therapyDrug
An approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting
Zoledronic AcidDrug
Also called Reclast, Zometa
5 mg zoledronic acid administered at a constant infusion rate
Standard of CareOther
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.

Study groups in NCT00556374
Study group	Role	What they receive
Denosumab	Experimental	Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy. Receives: Biological: Denosumab; Drug: Non-steroidal aromatase inhibitor therapy
Placebo	Placebo comparator	Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy. Receives: Drug: Placebo; Drug: Non-steroidal aromatase inhibitor therapy
SubStudy: Zoledronic Acid	Experimental	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. Receives: Drug: Zoledronic Acid
Substudy: Standard of Care	Other	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. Receives: Other: Standard of Care

What is being measured

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

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.
Measured: 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 (8)

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.
Measured: Baseline and Month 36
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.
Measured: Baseline and Month 36
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.
Measured: Baseline and Month 36
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.
Measured: 36 months
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.
Measured: 36 months
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.
Measured: 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
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.
Measured: From randomization until end of main study, maximum time on main study was 152 months
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause.
Measured: Randomization until end of main study, maximum duration of main study was 152 months

Timeline

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

18 Dec 200626 Jul 2022

First posted12 Nov 2007 (estimated)
Study start18 Dec 2006
Primary completion7 Oct 2014
Study completion26 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 3,420 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00556374
Sponsor's protocol ID: 20050209
Other IDs: ABCSG-18, 2005-005275-15, 2005
Status last verified: Jun 2023
First submitted: 8 Nov 2007
Last updated: 27 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

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
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
Gnant M, Frantal S, Pfeiler G, Steger GG, Egle D, Greil R, Fitzal F, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Artner-Matuschek S, Kainberger F, Ritter M, Rinnerthaler G, Sevelda P, Bergh J, Kacerovsky-Strobl S, Suppan C, Brunner C, Deutschmann C, Gampenrieder SP, Fohler H, Jakesz R, Fesl C, Singer C. Long-Term Outcomes of Adjuvant Denosumab in Breast Cancer. NEJM Evid. 2022 Dec;1(12):EVIDoa2200162. doi: 10.1056/EVIDoa2200162. Epub 2022 Nov 18.
PubMed 38319865
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Phase 3 Study to Determine the Treatment Effect of Denosumab in Subjects With Non-Metastatic Breast Cancer Receiving Aromatase Inhibitor Therapy.
ClinicalTrials.gov ID: NCT00556374
Acronym / sponsor ID: 20050209
Conditions: Breast Cancer
Keywords: confirmed adenocarcinoma, non-metastatic breast cancer, estrogen receptor positive, progesterone receptor positive, non-steroidal aromatase, aromatase inhibitor therapy, postmenopausal woman, adjuvant chemotherapy
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 3,420 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Collaborators: Austrian Breast & Colorectal Cancer Study Group
Study start: 18 Dec 2006 (actual)
Primary completion: 7 Oct 2014 (actual)
Study completion: 26 Jul 2022 (actual)
First posted: 12 Nov 2007 (estimated)
Results: Posted 6 Nov 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Denosumab	Experimental	Biological: Denosumab, Drug: Non-steroidal aromatase inhibitor therapyParticipants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Placebo	Placebo comparator	Drug: Placebo, Drug: Non-steroidal aromatase inhibitor therapyParticipants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
SubStudy: Zoledronic Acid	Experimental	Drug: Zoledronic AcidEligible 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.
Substudy: Standard of Care	Other	Other: Standard of CareEligible 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.

Who may qualify

Ages: 45 to 100 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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:
Follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range;

Key exclusion criteria (39 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboAlso: Administered as a subcutaneous injection	Drug	Placebo
DenosumabAlso: Prolia®Administered as a subcutaneous injection	Biological	Denosumab
Non-steroidal aromatase inhibitor therapyAn approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting	Drug	Denosumab, Placebo
Zoledronic AcidAlso: Reclast, Zometa5 mg zoledronic acid administered at a constant infusion rate	Drug	SubStudy: Zoledronic Acid
Standard of CareStandard 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.	Other	Substudy: Standard of Care

Primary outcome

Time to First Clinical Fracture
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
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.

8 secondary outcomes

Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites
Time frame: Baseline and Month 36
Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites
Time frame: Baseline and Month 36
Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites
Time frame: Baseline and Month 36
Number of Participants With New Vertebral Fractures
Time frame: 36 months
Number of Participants With New or Worsening Vertebral Fractures
Time frame: 36 months
Disease-free Survival (DFS)
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
Bone Metastases-free Survival (BMFS)
Time frame: From randomization until end of main study, maximum time on main study was 152 months
Overall Survival (OS)
Time frame: Randomization until end of main study, maximum duration of main study was 152 months

Results and safety

Results posted to the registry on 6 Nov 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	1,709	1,242
Denosumab	1,711	1,362

Primary outcome: Time to First Clinical Fracture

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. Median (95% Confidence Interval). Unit: Days

Measure	Placebo n = 1709	Denosumab n = 1711
Value	NA (NA to NA)	NA (NA to NA)

Placebo vs Denosumab: Hazard Ratio (HR): 0.504 (95% CI 0.39 to 0.65), p <0.0001, Cox Proportional Hazards Model

Population analysed: Full Analysis Set: all randomized participants

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Double-blind Phase: Placebo	515 of 1,690 (30.5%)	838 of 1,690 (49.6%)	Not reported
Double-blind Phase: Denosumab	521 of 1,709 (30.5%)	882 of 1,709 (51.6%)	Not reported
Open-label Phase: Placebo/Denosumab	40 of 245 (16.3%)	0 of 245 (0%)	Not reported
Open-label Phase: Denosumab/Denosumab	0 of 1 (0%)	0 of 1 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26040499Gnant 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.
Derived from this study: PubMed 38979716Adams 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.
Derived from this study: PubMed 38319865Gnant M, Frantal S, Pfeiler G, Steger GG, Egle D, Greil R, Fitzal F, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Artner-Matuschek S, Kainberger F, Ritter M, Rinnerthaler G, Sevelda P, Bergh J, Kacerovsky-Strobl S, Suppan C, Brunner C, Deutschmann C, Gampenrieder SP, Fohler H, Jakesz R, Fesl C, Singer C. Long-Term Outcomes of Adjuvant Denosumab in Breast Cancer. NEJM Evid. 2022 Dec;1(12):EVIDoa2200162. doi: 10.1056/EVIDoa2200162. Epub 2022 Nov 18.
Derived from this study: PubMed 35334418Minichsdorfer 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.
Derived from this study: PubMed 30795951Gnant 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.
AmgenTrials clinical trials websiteLink provided by the sponsor.
Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

46 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Denosumab, Non-steroidal aromatase inhibitor therapy and Zoledronic Acid in people with Breast Cancer, run by Amgen at 46 sites in 2 countries.

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 13 inclusion and 39 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: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in Austria, Sweden. 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 6 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Time to First Clinical Fracture (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). 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 NCT00556374, which also lists 5 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 27 Jul 2023.