Advanced Breast CancerNCT07225790
Emulation of the MONARCH-3 Trial Using Specialty Oncology Electronic Health Records Databases
An observational study of Advanced Breast Cancer, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- Initiation of abemaciclib plus letrozole/anastrozole and Initiation of letrozole/anastrozole
- How many people
- 3,883 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2025to 31 Jan 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- Women only
- Adult, Older adult
Study population: Postmenopausal women with ER/PR-positive, HER2-negative locally advanced or metastatic breast cancer who receive treatment without curative intent
Who may be able to join
- Female aged ≥18 years at treatment initiation from 2017 - 2023
- Evidence of metastatic breast cancer (MBC)
- Documentation of Estrogen/Progesterone receptor-positive (ER/PR+)
- Documentation of Human Epidermal Growth Factor Receptor Negative (HER2-)
- ECOG performance status of 0 or 1 within 90 days of index date
Who cannot join
- CNS metastases
- Prior treatment with CKD4/6 inhibitor
- Prior or current treatment with chemotherapy or endocrine therapy other than letrozole/anastrozole for systemic anticancer therapy for MBC.
- Prior (neo-)adjuvant endocrine therapy
- Systemic anticancer therapy other than abemaciclib or letrozole/anastrozole
- Non-breast cancer malignancy other than basal/squamous cell skin cancer or carcinoma in situ of cervix
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
About this study
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Read the detailed description
Randomized controlled trials (RCTs) are generally regarded as the gold-standard of evidence for establishing efficacy of medical products. However, real-world data (RWD) are increasingly used to complement evidence from RCTs. Yet, to have confidence in the accuracy of non-interventional studies medical products and their outcomes in oncology, investigators need to know what questions can be validly answered, with which non-interventional study designs, and which analysis methods are appropriate, given the data that is available. Building on a process from the RCT DUPLICATE initiative1-4 EmulatioN of Comparative Oncology trials with Real-world Evidence (ENCORE) is part of the expansion project specific to oncology and aims to emulate 12 randomized oncology RCTs using multiple EHR data sources.
The purpose of this protocol is to describe the emulation of the MONARCH-3 trial. MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole/anastrozole, daily.
- Conditions
- Advanced Breast Cancer
- Being tested
- Initiation of abemaciclib plus letrozole/anastrozole, Initiation of letrozole/anastrozole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Initiation of abemaciclib plus letrozole/anastrozoleDrug
Any doses and frequency observed in clinical practice will be allowed
Initiation of letrozole/anastrozoleDrug
Any doses and frequency observed in clinical practice will be allowed
| Study group | Role | What they receive |
|---|---|---|
| Initiation of abemaciclib plus letrozole/anastrozole | Any doses and frequency observed in clinical practice will be allowed Receives: Drug: Initiation of abemaciclib plus letrozole/anastrozole | |
| Initiation of letrozole/anastrozole | Any doses and frequency observed in clinical practice will be allowed Receives: Drug: Initiation of letrozole/anastrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to all-cause mortality (overall survival)
Hazard ratio (95% CI)
Measured: From time of initiation of therapy through the earliest of death from any cause (the primary outcome of interest) or end of data availability (depending on specialty oncology registry data provider, end of data ranges from June 2023 to April 2024)
Secondary outcomes (1)
Time to next treatment (TTNT)
Hazard ratio (95% CI)
Measured: From time of initiation of therapy through the earliest of TTNT, death from any cause, or end of data availability (depending on specialty oncology registry data provider, end of data ranges from June 2023 to April 2024)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2025
- Study start3 Nov 2025
- Primary completion31 Jan 2026
- Study completion31 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 3,883 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Women's HospitalDenys Shay, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07225790
- Sponsor's protocol ID
- 2022P002556-ENC-MONARCH-3
- Other IDs
- 75F40122C00181
- Status last verified
- Nov 2025
- First submitted
- 5 Nov 2025
- Last updated
- 12 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emulation of the MONARCH-3 Trial Using Specialty Oncology Electronic Health Records Databases
- ClinicalTrials.gov ID
- NCT07225790
- Acronym / sponsor ID
- 2022P002556-ENC-MONARCH-3
- Conditions
- Advanced Breast Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,883 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 3 Nov 2025 (actual)
- Primary completion
- 31 Jan 2026 (actual)
- Study completion
- 31 Jan 2026 (actual)
- First posted
- 10 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
Randomized controlled trials (RCTs) are generally regarded as the gold-standard of evidence for establishing efficacy of medical products. However, real-world data (RWD) are increasingly used to complement evidence from RCTs. Yet, to have confidence in the accuracy of non-interventional studies medical products and their outcomes in oncology, investigators need to know what questions can be validly answered, with which non-interventional study designs, and which analysis methods are appropriate, given the data that is available. Building on a process from the RCT DUPLICATE initiative1-4 EmulatioN of Comparative Oncology trials with Real-world Evidence (ENCORE) is part of the expansion project specific to oncology and aims to emulate 12 randomized oncology RCTs using multiple EHR data sources.
The purpose of this protocol is to describe the emulation of the MONARCH-3 trial. MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole/anastrozole, daily.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Initiation of abemaciclib plus letrozole/anastrozole | – | Drug: Initiation of abemaciclib plus letrozole/anastrozoleAny doses and frequency observed in clinical practice will be allowed |
| Initiation of letrozole/anastrozole | – | Drug: Initiation of letrozole/anastrozoleAny doses and frequency observed in clinical practice will be allowed |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Age groups
- Adult, Older adult
- Study population
- Postmenopausal women with ER/PR-positive, HER2-negative locally advanced or metastatic breast cancer who receive treatment without curative intent
Key inclusion criteria (5 listed)
- Female aged ≥18 years at treatment initiation from 2017 - 2023
- Evidence of metastatic breast cancer (MBC)
- Documentation of Estrogen/Progesterone receptor-positive (ER/PR+)
- Documentation of Human Epidermal Growth Factor Receptor Negative (HER2-)
- ECOG performance status of 0 or 1 within 90 days of index date
Key exclusion criteria (6 listed)
- CNS metastases
- Prior treatment with CKD4/6 inhibitor
- Prior or current treatment with chemotherapy or endocrine therapy other than letrozole/anastrozole for systemic anticancer therapy for MBC.
- Prior (neo-)adjuvant endocrine therapy
- Systemic anticancer therapy other than abemaciclib or letrozole/anastrozole
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 |
|---|---|---|
| Initiation of abemaciclib plus letrozole/anastrozoleAny doses and frequency observed in clinical practice will be allowed | Drug | Initiation of abemaciclib plus letrozole/anastrozole |
| Initiation of letrozole/anastrozoleAny doses and frequency observed in clinical practice will be allowed | Drug | Initiation of letrozole/anastrozole |
Primary outcome
Time to all-cause mortality (overall survival)
Time frame: From time of initiation of therapy through the earliest of death from any cause (the primary outcome of interest) or end of data availability (depending on specialty oncology registry data provider, end of data ranges from June 2023 to April 2024)
Hazard ratio (95% CI)
1 secondary outcome
Time to next treatment (TTNT)
Time frame: From time of initiation of therapy through the earliest of TTNT, death from any cause, or end of data availability (depending on specialty oncology registry data provider, end of data ranges from June 2023 to April 2024)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
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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.
Shirley Wang, PhD, ScM principal investigator
Brigham and Women's Hospital
Denys Shay, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Advanced Breast Cancer, run by Brigham and Women's Hospital at 1 site in United States.
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 5 inclusion and 6 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 12 May 2026. 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 United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 all-cause mortality (overall survival) (time frame: From time of initiation of therapy through the earliest of death from any cause (the primary outcome of interest) or end of data availability (depending on specialty oncology registry data provider, end of data ranges from June 2023 to April 2024)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 May 2026.