Breast CancerNCT07910565
Prospective Study to Evaluate the Clinical Utility of ctDNA Tumor Fraction (TF) for Detection of Estrogen Receptor 1 (ESR1) Mutations in (Human Epidermal Growth Factor Receptor) HR+/HER2- Metastatic Breast Cancer (MBC)
A study testing FoundationOne® Liquid CDx (F1LCDx) and Reflex tissue biopsy in people with Breast Cancer and Metastatic Breast Cancer, run by Yale University at 1 site in United States.
Trial summary
This is a prospective, single center, single-arm interventional study to evaluate the clinical utility of protocol-mandated diagnostic testing algorithm incorporating liquid biopsy and reflex tissue biopsy NGS for detection of ESR1 mutations in HR+/HER- metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Metastatic Breast Cancer, HR+/HER- Metastatic Breast Cancer
- What is being tested?
- FoundationOne® Liquid CDx (F1LCDx) and Reflex tissue biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Oct 2031
- 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
- Diagnosis of metastatic breast cancer that is hormone receptor-positive (ER≥10%), HER2 low or negative (defined as HER2 Imunohistochemistry (IHC) 0, 1+ or IHC 2+/In Situ Hybridization (ISH)-).
- Progression of metastatic breast cancer that is hormone receptor-positive (ER≥10%), HER2 low or negative (defined as HER2 IHC 0, 1+ or IHC 2+/ISH-) while on systemic therapy.
- Currently receiving or have previously received aromatase inhibitor therapy.
Who cannot join
- Patients with locally or regionally recurrent breast cancer without evidence of metastatic disease.
- De novo metastatic breast cancer.
- Presence of symptomatic metastatic visceral crisis.
- Participants with inflammatory breast cancer.
- Intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion).
- Diagnosis of any other malignancy within 5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or second primary breast cancer.
- Other conditions that, in the opinion of the treating investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
- Pregnant and breastfeeding women are excluded from the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Yale New Haven Hospital - Yale Cancer Center
New Haven, Connecticut, 06520
About this study
Official title: Prospective Study to Evaluate the Clinical Utility of ctDNA Tumor Fraction (TF) for Detection of ESR1 Mutations in HR-positive HER2-negative Metastatic Breast Cancer (MBC)
This is a prospective, single center, single-arm interventional study to evaluate the clinical utility of protocol-mandated diagnostic testing algorithm incorporating liquid biopsy and reflex tissue biopsy NGS for detection of ESR1 mutations in HR+/HER- metastatic breast cancer.
Read the detailed description
Participants are prospectively assigned to undergo ctDNA testing with FoundationOne® Liquid CDx (F1LCDx) at protocol-defined clinical decision points. Participants with an indeterminate negative F1LCDx result (ctDNA TF <1% and negative for ESR1mut) are assigned to undergo reflex tissue biopsy NGS unless deemed medically unsafe. The protocol does not mandate treatment selection; treating clinicians retain full discretion regarding therapy.All research-related procedures will be performed at the time of standard of care clinical visits. No extra visits outside of routine care are required. For participants with algorithm-detected ESR1 mutations, serial Electronic Medical Record review will be performed for up to 2 years to track subsequent treatment patterns, progression events, and survival status to assess other clinical outcomes associated with subsequent SERD-based regimens compared with historical clinical trial benchmarks.
This study will guide clinical decision-making for acquiring new tissue specimens following an indeterminate negative ESR1mut result from liquid biopsy, which is a critical step to ensure accurate detection of actionable mutations and enable the selection of the most appropriate targeted therapy
- Being tested
- FoundationOne® Liquid CDx (F1LCDx), Reflex tissue biopsy
- Keywords
- ESR1 mutations, Next-Generation sequencing (NGS), Liquid Biopsy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FoundationOne® Liquid CDx (F1LCDx)Diagnostic test
Blood test that analyzes cancer-related genes from a single blood draw
Reflex tissue biopsyDiagnostic test
Reflex tissue biopsy using an Next-generation sequencing (NGS) test
| Study group | Role | What they receive |
|---|---|---|
| HR+/HER- metastatic breast cancer at diagnosis or experiencing disease progression | Experimental | Participants with ESR1 mutations in HR+/HER- metastatic breast cancer undergoing tissue biopsy for ctDNA Tumor Fraction (TF) testing using next-generation sequencing (NGS) after an indeterminate negative result in liquid biopsy (F1LCDx). Receives: Diagnostic Test: FoundationOne® Liquid CDx (F1LCDx); Diagnostic Test: Reflex tissue biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with ESR1 mutations detected by reflex tissue NGS
Among participants with an indeterminate-negative liquid biopsy result (negative for ESR1 mutations and ctDNA tumor fraction below 1%), measure the number of participants with an ESR1 mutation detected by reflex tissue NGS performed according to the study algorithm.
Measured: From enrollment through study completion (up to 5 years)
Secondary outcomes (9)
Progression-free survival (PFS)
Time from initiation of the first selective estrogen receptor degrader (SERD) after ESR1 mutation detection until objective disease progression, assessed using RECIST version 1.1 when available, or death from any cause, whichever occurs first.
Measured: Up to 2 years after positive ESR1 mutation detection
Rate of ESR1 mutation detection by liquid biopsy and ctDNA tumor fraction
Rate of ESR1 mutation detection by FoundationOne Liquid CDx (F1LCDx), stratified by ctDNA tumor fraction below 1% versus 1% or greater.
Measured: Throughout the study, up to 5 years
Reflex Tissue NGS testing rate
Number of participants with an indeterminate-negative liquid biopsy result who undergo reflex tissue biopsy and NGS within the protocol-defined timeframe.
Measured: Within the reflex testing time frame during the study, up to 5 years
Number participants initiating Selective Estrogen Receptor Degraders (SERD) therapy
Number participants initiating SERD therapy after ESR1 mutation detection
Measured: Throughout the study, up to 5 years
Number participants SERD therapy by SERD agent
Number participants initiating SERD therapy after ESR1 mutation detection. Report counts by SERD agent, with FDA-approved SERDs grouped by class as applicable.
Measured: Throughout the study, up to 5 years
Actionable genomic alterations detected by liquid biopsy and tissue NGS.
Rtes of actionable genomic alterations detected by F1LCDx and tissue NGS.
Measured: Throughout the study, up to 5 years
Other genomic alterations detected at disease progression
Rates of driver and acquired genomic alterations detected at progression by F1LCDx or tissue NGS that were absent from prior tissue comprehensive genomic profiling (CGP). Acquired alterations are those absent from tissue CGP at diagnosis but newly detected at progression.
Measured: At disease progression during the study, up to 5 years
Correlation of HRR gene findings with variant origin and germline confirmation
Assess the relationship between homologous recombination repair (HRR) gene detection, variant origin prediction, germline banner classification when F1LCDx is performed, and confirmation of germline alterations by orthogonal testing.
Measured: During the study, when the relevant genomic and confirmatory testing results are available, up to 5 years
Correlation of HER2 status with ERBB2 copy number
Assess the relationship between HER2-low or HER2-negative status and ERBB2 copy number results when F1CDx is performed.
Measured: During the study, when the relevant HER2 status and genomic results are available, up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2026
- Study startNov 2026 (estimated)
- Primary completionOct 2031 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 155 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation Medicine
- Responsible party
- Sponsor
- Investigators
- Jing Du, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07910565
- Sponsor's protocol ID
- 2000038562
- Status last verified
- Nov 2026
- First submitted
- 26 Oct 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study to Evaluate the Clinical Utility of ctDNA Tumor Fraction (TF) for Detection of ESR1 Mutations in HR-positive HER2-negative Metastatic Breast Cancer (MBC)
- ClinicalTrials.gov ID
- NCT07910565
- Acronym / sponsor ID
- 2000038562
- Keywords
- ESR1 mutations, Next-Generation sequencing (NGS), Liquid Biopsy
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 155 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Foundation Medicine
- Study start
- Nov 2026 (estimated)
- Primary completion
- Oct 2031 (estimated)
- Study completion
- Oct 2031 (estimated)
- First posted
- 2 Nov 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.
This is a prospective, single center, single-arm interventional study to evaluate the clinical utility of protocol-mandated diagnostic testing algorithm incorporating liquid biopsy and reflex tissue biopsy NGS for detection of ESR1 mutations in HR+/HER- metastatic breast cancer.
Detailed description
Participants are prospectively assigned to undergo ctDNA testing with FoundationOne® Liquid CDx (F1LCDx) at protocol-defined clinical decision points. Participants with an indeterminate negative F1LCDx result (ctDNA TF <1% and negative for ESR1mut) are assigned to undergo reflex tissue biopsy NGS unless deemed medically unsafe. The protocol does not mandate treatment selection; treating clinicians retain full discretion regarding therapy.All research-related procedures will be performed at the time of standard of care clinical visits. No extra visits outside of routine care are required. For participants with algorithm-detected ESR1 mutations, serial Electronic Medical Record review will be performed for up to 2 years to track subsequent treatment patterns, progression events, and survival status to assess other clinical outcomes associated with subsequent SERD-based regimens compared with historical clinical trial benchmarks.
This study will guide clinical decision-making for acquiring new tissue specimens following an indeterminate negative ESR1mut result from liquid biopsy, which is a critical step to ensure accurate detection of actionable mutations and enable the selection of the most appropriate targeted therapy
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HR+/HER- metastatic breast cancer at diagnosis or experiencing disease progression | Experimental | Diagnostic Test: FoundationOne® Liquid CDx (F1LCDx), Diagnostic Test: Reflex tissue biopsyParticipants with ESR1 mutations in HR+/HER- metastatic breast cancer undergoing tissue biopsy for ctDNA Tumor Fraction (TF) testing using next-generation sequencing (NGS) after an indeterminate negative result in liquid biopsy (F1LCDx). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of metastatic breast cancer that is hormone receptor-positive (ER≥10%), HER2 low or negative (defined as HER2 Imunohistochemistry (IHC) 0, 1+ or IHC 2+/In Situ Hybridization (ISH)-).
- Progression of metastatic breast cancer that is hormone receptor-positive (ER≥10%), HER2 low or negative (defined as HER2 IHC 0, 1+ or IHC 2+/ISH-) while on systemic therapy.
- Currently receiving or have previously received aromatase inhibitor therapy.
Key exclusion criteria (8 listed)
- Patients with locally or regionally recurrent breast cancer without evidence of metastatic disease.
- De novo metastatic breast cancer.
- Presence of symptomatic metastatic visceral crisis.
- Participants with inflammatory breast cancer.
- Intact uterus with a history of endometrial intraepithelial neoplasia (atypical endometrial hyperplasia or higher-grade lesion).
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 |
|---|---|---|
| FoundationOne® Liquid CDx (F1LCDx)Blood test that analyzes cancer-related genes from a single blood draw | Diagnostic test | HR+/HER- metastatic breast cancer at diagnosis or experiencing disease progression |
| Reflex tissue biopsyReflex tissue biopsy using an Next-generation sequencing (NGS) test | Diagnostic test | HR+/HER- metastatic breast cancer at diagnosis or experiencing disease progression |
Primary outcome
Number of participants with ESR1 mutations detected by reflex tissue NGS
Time frame: From enrollment through study completion (up to 5 years)
Among participants with an indeterminate-negative liquid biopsy result (negative for ESR1 mutations and ctDNA tumor fraction below 1%), measure the number of participants with an ESR1 mutation detected by reflex tissue NGS performed according to the study algorithm.
9 secondary outcomes
Progression-free survival (PFS)
Time frame: Up to 2 years after positive ESR1 mutation detection
Rate of ESR1 mutation detection by liquid biopsy and ctDNA tumor fraction
Time frame: Throughout the study, up to 5 years
Reflex Tissue NGS testing rate
Time frame: Within the reflex testing time frame during the study, up to 5 years
Number participants initiating Selective Estrogen Receptor Degraders (SERD) therapy
Time frame: Throughout the study, up to 5 years
Number participants SERD therapy by SERD agent
Time frame: Throughout the study, up to 5 years
Actionable genomic alterations detected by liquid biopsy and tissue NGS.
Time frame: Throughout the study, up to 5 years
Other genomic alterations detected at disease progression
Time frame: At disease progression during the study, up to 5 years
Correlation of HRR gene findings with variant origin and germline confirmation
Time frame: During the study, when the relevant genomic and confirmatory testing results are available, up to 5 years
Correlation of HER2 status with ERBB2 copy number
Time frame: During the study, when the relevant HER2 status and genomic results are available, up to 5 years
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 5 Nov 2026.
- Individual participant dataSharing planned: No
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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.
Jing Du, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FoundationOne® Liquid CDx (F1LCDx) and Reflex tissue biopsy in people with Breast Cancer and Metastatic Breast Cancer, run by Yale University 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 3 inclusion and 8 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 5 Nov 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?
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 Carl Brown (203-785-4096, carl.brown@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with ESR1 mutations detected by reflex tissue NGS (time frame: From enrollment through study completion (up to 5 years)). 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 5 Nov 2026.