HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole)ESRANCT07817212
ESR1Real World Assessment Prevalence Study
A study testing ESR1 testing in people with HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole), run by Institut fuer Frauengesundheit at 21 sites in Germany.
Trial summary
Many patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer in the first therapy line is endocrine sensitive. For these patients the established 1st line standard therapy is a combination of a CDK4/6 inhibitor and an aromatase inhibitor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole)
- What is being tested?
- ESR1 testing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,550 participants
- Where
- 21 sitesGermany
- Study dates
- 1 Oct 2026to 31 Dec 2027
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be female or male and aged ≥ 18 years on the day of signing informed consent
- Patient has locally advanced or metastatic breast cancer not amenable to curative treatment
- Patient has HER2- breast cancer confirmed by local laboratory, defined as a negative in situ hybridization test or an IHC status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory)
- Histologically confirmed ER-positive and/ or PgR-positive breast cancer determined by core biopsy according to local in-house standard
- Patient has already initiated or is about to initiate first-line therapy with a CDK4/6 inhibitor (any CDK4/6i) in combination with an aromatase inhibitor (non-steroidal AI). Treatment must be intended as first-line systemic therapy for advanced or metastatic disease
- Information about prior oncological therapies against the HR+/HER2- BC must be available
- Data about histo-pathological report must be available, including hormone receptor status, tumor histology, tumor grading and HER2 immunohistochemistry
- Inclusion in the study occurs as a single, one-time event for each patient, within one of the 9 defined cohorts
Who cannot join
- Patients with an interruption of ongoing first-line CDK4/6i plus AI therapy exceeding 1 month for either CDK4/6i or AI
- Patients receiving any other systemic anticancer therapy for HR+/HER2- aBC, except for LHRH agonists, bisphosphonates, or denosumab
- Clinical evidence of progression at the timepoint of study inclusion
- Patients have already completed ≥ 1L of systemic therapy for aBC
Trial locations and contacts
21 sites in 1 country. Contact the study team or a site near you to ask about taking part.
21 sites in 1 country
Germany21 sites
ANregiomed gKU, AöR, Klinikum Ansbach
Ansbach, 91522
Thomas Hildebrandt, PD Dr., +49 981 484 2256, thomas.hildebrandt@anregiomed.de
Hämato-Onkologische Praxis im Medicum; Brustzentrum
Bremen
Ralf Meyer, Dr., +49 421 6960960, ralfmeyer@home-bremen.com
Allgemeines Krankenhaus Celle; Brustzentrum
Celle, 29223
Michael Berghorn, Dr., +49 5141 721151, michael.berghorn@akh-celle.de
Universitätsklinikum Carl Gustav Carus Dresden, Frauenklinik
Dresden, 01307
Theresa Link, Dr., +49 351 4586863
Kostara Gyn. Onkoloy Clinic Research UG
Düsseldorf, 40235
Athina Kostara, Dr., +49 211 53809241, athina.kostara@gynoncology-cr.de
Universitätsklinikum Erlangen, Frauenklinik
Erlangen, 91054
Peter Andreas Fasching, Prof. Dr., +4991318533572, peter.fasching.studien@uk-erlangen.de
Universitätsklinikum; Frauenheilkunde, Geburtshilfe & Reproduktionsmedizin
Homburg, 66421
Julia Radosa, Prof. Dr., +49 6841 16280, julia.radosa@uks.eu
Frauenarztpraxis Baerens
Ilsede, 31241
Dirk-Toralf Baerens, +49 5172 2221, baerens@online.de
OncoStudies Lörrach, Onkologie Dreiländereck
Loerrach, 79539
Gwen-Jana Töppler, Dr., +49 7621 5791570, toeppler@onkologie-loerrach.de
Rotkreuzklinikum München; Brustzentrum
München, 80637
Michael Braun, Prof., +49 89 130330, Michael.Braun@swmbrk.de
Hämatologie OnkologieMünchen Pasing MVZ GmbH
München, 81241
Matthias Zingerle, Dr., +49 898299660, zingerle@onkolohie-pasing.de
MVZ Media Vita am St. Franziskus Hospital; Frauenklinik
Münster, 48145
Christian Eichler, PD Dr., +49 251 9355580, christian.eichler@sfh-muenster.de
Universitätsklinikum Münster; Frauenklinik
Münster, 48727
Opitz Carl, Dr., +49 251 8344111, carl.opitz@ukmuenster.de
Klinikum Ernst von Bergmann; Frauenheilkunde
Potsdam, 14467
Dorothea Fischer, Prof. Dr., +49 331 241 35602, Dorothea.Fischer@klinikumevb.de
medicum Rosenheim MVZ GmbH; Innere Onkologie
Rosenheim, 83022
Rudolf Pihusch, Prof. Dr., +49 803134511, Rudolf.Pihusch@pihusch.de
Kreiskrankenhaus Torgau; Brustzentrum
Torgau, 04860
Eike Simon, Dr., +49 3421 77-2520, simon@kkh-torgau.de
Universitätsklinikum Tübingen; Department für Frauengesundheit
Tübingen, 72076
Andreas Hartkopf, Prof. Dr., +49 7071 2982211, andreas.hartkopf@med.uni-tuebingen.de
Medizinische Studiengesellschaft Nord-West GmbH; Onkologie
Westerstede, 26655
Jan Janssen, Dr., +49 4488521880, gensch-janssen@t-online.de
Helios Dr. Horst Schmidt Kliniken; Gynäkologie
Wiesbaden, 65199
Michael Eichbaum, Prof. Dr., +49 611 432377, michael.eichbaum@helios-gesundheit.de
Frauenärzte am Schloß; Praxis für Gynäkologie und Geburtshilfe
Wolfenbüttel, 38304
Julia von Ehr, Dr., +49 5331 2510, ju.vonehr@gmail.com
Universitätsklinik Würzburg; Frauenklinik und Poliklinik
Würzburg, 97080
Jessica Salmen, Dr., +49 931 20125194, salmen_J@ukw.de
About this study
Many patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer in the first therapy line is endocrine sensitive. For these patients the established 1st line standard therapy is a combination of a CDK4/6 inhibitor and an aromatase inhibitor. This combination therapy is usually given until clinical progression.
Recent studies suggest that a detection of a somatic ESR1 mutation in the ctDNA can be clinically used to prompt an earlier change from the aromatase inhibitor to a selective estrogen receptor degrader.
Read more
For implementation in the clinical routine it is important to gain knowledge about the dynamics of ESR1 mutation in HR+/HER2- advanced breast cancer patients during their first line therapy. At the beginning of the first line therapy about 5-8% of patients show an ESR1 mutation. An identification of patients with resistance to aromatase inhibitors at that timepoint might not be feasible and cost-efficient. At the timepoint of clinical progression up to 30-40% of patients will have acquired an ESR1 mutation. Knowledge about the mutation frequencies at different timepoints will be very helpful to direct testing strategies for implementing testing broadly in a population.
The aim of this study is to test ESR1 mutation frequencies in groups of patients (single time test per patient) with no clinical progression and different durations under first-line treatment with aromatase inhibitor and CDK4/4 inhibitor.
- Being tested
- ESR1 testing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ESR1 testingDiagnostic test
Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
| Study group | Role | What they receive |
|---|---|---|
| Cohort (0m) | Experimental | Before start of the 1L treatment (anticipated AI + CDK4/6i) Receives: Diagnostic Test: ESR1 testing |
| Cohort (6-8m): | Experimental | Patients in months 6, 7 or 8 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
| Cohort (9-11m) | Experimental | Patients in months 9, 10 or 11 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
| Cohort (12-14m) | Experimental | Patients in months 12, 13 or 14 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
| Cohort (15-17m) | Experimental | Patients in months 15, 16 or 17 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
| Cohort (18-20m) | Experimental | Patients in months 18, 19 or 20 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
| Cohort (21-23m) | Experimental | Patients in months 21, 22 or 23 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
| Cohort (24-26m) | Experimental | Patients in months 24, 25 or 26 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
| Cohort (27-29m) | Experimental | Patients in months 27, 28 or 29 of the 1L treatment Receives: Diagnostic Test: ESR1 testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
PO1
mutation frequency of ESR1 mutations as assessed in blood sample
Measured: Day 1
Secondary outcomes (8)
SO1
ESR1 mutation frequencies according to age and BMI
Measured: Day 1
SO2
ESR1 mutation frequencies according to type of CDK4/6i therapy
Measured: Day 1
SO3
ESR1 mutation frequencies according to type of aromatase inhibitor
Measured: Day 1
SO3
ESR1 mutation frequencies according to menopausal status
Measured: Day 1
SO4
ESR1 mutation frequencies according to HER2 status (HER2 0, HER2 ultralow, HER2 low)
Measured: Day 1
SO5
ESR1 mutation frequencies according to extent of estrogen and progesterone receptor expression
Measured: Day 1
SO6
ESR1 mutation frequencies according to tumor grading
Measured: Day 1
SO7
ESR1 mutation frequencies according to previous therapies (de novo patients vs. previous adjuvant therapy)
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2026
- Study start1 Oct 2026 (estimated)
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole)Studies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,550 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut fuer Frauengesundheit
- Sponsor type
- University, hospital or other
- Collaborators
- AGO Breast (Arbeitsgemeinschaft Gynäkologische Onkologie), data4treat GmbH, BioMedStatistics GmbH, ClinSol GmbH & Co KG, Universitätsklinikum Erlangen
- Responsible party
- Sponsor
- Investigators
- Peter Andreas Fasching, Prof. Dr., Study director, AGO-B e.V. c/o Frauenklinik des Universitätsklinikums ErlangenVolkmar Müller, Prof. Dr., Study chair, Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für GynäkologieTanja Fehm, Prof. Dr., Study chair, Frauenklinik des Universitätsklinikums Düsseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07817212
- Sponsor's protocol ID
- IFG-01-2026
- Acronym
- ESRA
- Status last verified
- Sep 2026
- First submitted
- 8 Sep 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ESR1Real World Assessment Prevalence Study
- ClinicalTrials.gov ID
- NCT07817212
- Acronym / sponsor ID
- ESRA / IFG-01-2026
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,550 participants (estimated)
- Lead sponsor
- Institut fuer FrauengesundheitUniversity, hospital or other
- Collaborators
- AGO Breast (Arbeitsgemeinschaft Gynäkologische Onkologie), data4treat GmbH, BioMedStatistics GmbH, ClinSol GmbH & Co KG, Universitätsklinikum Erlangen
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 14 Sep 2026 (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.
Many patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer in the first therapy line is endocrine sensitive. For these patients the established 1st line standard therapy is a combination of a CDK4/6 inhibitor and an aromatase inhibitor. This combination therapy is usually given until clinical progression.
Recent studies suggest that a detection of a somatic ESR1 mutation in the ctDNA can be clinically used to prompt an earlier change from the aromatase inhibitor to a selective estrogen receptor degrader.
For implementation in the clinical routine it is important to gain knowledge about the dynamics of ESR1 mutation in HR+/HER2- advanced breast cancer patients during their first line therapy. At the beginning of the first line therapy about 5-8% of patients show an ESR1 mutation. An identification of patients with resistance to aromatase inhibitors at that timepoint might not be feasible and cost-efficient. At the timepoint of clinical progression up to 30-40% of patients will have acquired an ESR1 mutation. Knowledge about the mutation frequencies at different timepoints will be very helpful to direct testing strategies for implementing testing broadly in a population.
The aim of this study is to test ESR1 mutation frequencies in groups of patients (single time test per patient) with no clinical progression and different durations under first-line treatment with aromatase inhibitor and CDK4/4 inhibitor.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Cohort (0m) | Experimental | Diagnostic Test: ESR1 testingBefore start of the 1L treatment (anticipated AI + CDK4/6i) |
| Cohort (6-8m): | Experimental | Diagnostic Test: ESR1 testingPatients in months 6, 7 or 8 of the 1L treatment |
| Cohort (9-11m) | Experimental | Diagnostic Test: ESR1 testingPatients in months 9, 10 or 11 of the 1L treatment |
| Cohort (12-14m) | Experimental | Diagnostic Test: ESR1 testingPatients in months 12, 13 or 14 of the 1L treatment |
| Cohort (15-17m) | Experimental | Diagnostic Test: ESR1 testingPatients in months 15, 16 or 17 of the 1L treatment |
| Cohort (18-20m) | Experimental | Diagnostic Test: ESR1 testingPatients in months 18, 19 or 20 of the 1L treatment |
| Cohort (21-23m) | Experimental | Diagnostic Test: ESR1 testingPatients in months 21, 22 or 23 of the 1L treatment |
| Cohort (24-26m) | Experimental | Diagnostic Test: ESR1 testingPatients in months 24, 25 or 26 of the 1L treatment |
| Cohort (27-29m) | Experimental | Diagnostic Test: ESR1 testingPatients in months 27, 28 or 29 of the 1L treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject must be female or male and aged ≥ 18 years on the day of signing informed consent
- Patient has locally advanced or metastatic breast cancer not amenable to curative treatment
- Patient has HER2- breast cancer confirmed by local laboratory, defined as a negative in situ hybridization test or an IHC status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory)
- Histologically confirmed ER-positive and/ or PgR-positive breast cancer determined by core biopsy according to local in-house standard
- Patient has already initiated or is about to initiate first-line therapy with a CDK4/6 inhibitor (any CDK4/6i) in combination with an aromatase inhibitor (non-steroidal AI). Treatment must be intended as first-line systemic therapy for advanced or metastatic disease
Key exclusion criteria (4 listed)
- Patients with an interruption of ongoing first-line CDK4/6i plus AI therapy exceeding 1 month for either CDK4/6i or AI
- Patients receiving any other systemic anticancer therapy for HR+/HER2- aBC, except for LHRH agonists, bisphosphonates, or denosumab
- Clinical evidence of progression at the timepoint of study inclusion
- Patients have already completed ≥ 1L of systemic therapy for aBC
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 |
|---|---|---|
| ESR1 testingStudy procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion. | Diagnostic test | Cohort (0m), Cohort (12-14m), Cohort (15-17m), Cohort (18-20m), Cohort (21-23m), Cohort (24-26m), Cohort (27-29m), Cohort (6-8m):, Cohort (9-11m) |
Primary outcome
PO1
Time frame: Day 1
mutation frequency of ESR1 mutations as assessed in blood sample
8 secondary outcomes
SO1
Time frame: Day 1
SO2
Time frame: Day 1
SO3
Time frame: Day 1
SO3
Time frame: Day 1
SO4
Time frame: Day 1
SO5
Time frame: Day 1
SO6
Time frame: Day 1
SO7
Time frame: Day 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Individual participant dataSharing planned: Undecided
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.
Peter Andreas Fasching, Prof. Dr. study director
AGO-B e.V. c/o Frauenklinik des Universitätsklinikums Erlangen
Volkmar Müller, Prof. Dr. study chair
Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Gynäkologie
Tanja Fehm, Prof. Dr. study chair
Frauenklinik des Universitätsklinikums Düsseldorf
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ESR1 testing in people with HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole), run by Institut fuer Frauengesundheit at 21 sites in Germany.
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 8 inclusion and 4 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: opening soon, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Germany. 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?
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?
Contact Sponsor's study office (+49 9131 91880613, esra@ifg-erlangen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PO1 (time frame: Day 1). 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 14 Sep 2026.