Metastatic Breast CancerPhase 2ESTHERNCT05716516
STUDY02001740;22SCH740: Estradiol For ER+ Advanced Breast Cancer (ESTHER)
A Phase 2 study testing Estradiol in people with Metastatic Breast Cancer, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher rate of clinical benefit from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Estradiol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 4 May 2023to May 2027
- Phase
- Phase 2
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Post-menopausal women with ER+ breast cancer.
- Metastatic or locoregional recurrence not amenable to treatment with curative
- intent.
- Received ≥1 prior line of endocrine-based therapy (e.g., including tamoxifen, aromatase inhibitors, fulvestrant, or combinations) in the advanced/metastatic setting
Who cannot join
- During the study Treatment Phase with 17b-estradiol, no concurrent anti-cancer therapies are allowed with the following exceptions:
- Exception: Trastuzumab is allowed for the treatment of subjects with a history of HER2+ disease, and will be used at the physician's discretion.
- Exception: Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
- Any investigational cancer therapy in the last 3 weeks.
- Known CNS disease, unless clinically stable for ≥ 3 months.
- History of any of the following:
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- Deep venous thrombosis.
- Pulmonary embolism.
- Stroke.
- Acute myocardial infarction.
- Congestive heart failure.
- Previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%.
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, 1 recruiting
- Recruiting
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: Phase II Study of Estradiol Therapy to Target ER-Mutant and ER-Wild-Type ER+ Metastatic or Advanced Breast Cancer
Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher rate of clinical benefit from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer
Read the detailed description
Patients with endocrine-resistant breast cancer are eligible. Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined. Observational Phase (optional): After disease progression on 17b-estradiol, patients will be treated at their oncologist's discretion. Clinical benefit, progression-free survival, and objective response will be measured during this line of treatment of physician's choice until another instance of disease progression. In consented subjects who undergo a clinically indicated tumor biopsy of recurrent or metastatic disease prior to the start of 17b-estradiol treatment, when feasible, acquisition of additional tumor tissue is requested for research purposes. Optional: patients will be asked to provide tumor tissue via a research biopsy on Day 3-4 of 17b-estradiol treatment. Archived tumor tissue and clinical-grade tumor and plasma DNA/RNA sequencing results will be used for research purposes. Blood samples will be obtained at baseline, on Day 3-4 of 17b-estradiol therapy (optional), and upon disease progression on 17b-estradiol. Plasma and buffy coat will be extracted and frozen. Tumor tissue and plasma specimens will be analyzed to identify molecular biomarkers predictive of sensitivity/resistance to 17b-estradiol therapy
- Conditions
- Metastatic Breast Cancer
- Being tested
- Estradiol
- Keywords
- Metastatic, Locally advanced, Estradiol therapy, Estrogen therapy
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Also called Estrace
Estradiol is a therapeutic option for the treatment of advanced ER+ breast cancer
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Other | Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy Receives: Drug: Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate
The clinical benefit rate (complete responses + partial responses + stable disease at 24 weeks) will be ascertained and compared between subjects treated with 17b-estradiol harboring amplified/mutant ESR1 and wild-type ESR1.
Measured: 12 months
Secondary outcomes (4)
Objective response rate
The objective response rate (complete + partial responses) to the first 8 weeks of treatment with 17b-estradiol will be ascertained and compared between subjects harboring amplified/mutant ESR1 and wild-type ESR1.
Measured: 8 weeks
Progression-free survival
Progression-free survival with 17b-estradiol treatment will be ascertained and compared between subjects harboring amplified/mutant ESR1 and wild-type ESR1.
Measured: 12 months
Tumor Metabolic response
Tumor metabolic response will be defined as the best response at any time point per PERCIST. The metabolic response rate (complete + partial metabolic response) will be ascertained and compared between subjects treated with 17b-estradiol harboring amplified/mutant ESR1 and wild-type ESR1.
Measured: 12 months
Adverse event profiles
The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be collected
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2023
- Study start4 May 2023
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Muhammad.Z.Afzal, Dartmouth-Hitchcock Medical Center
- Investigators
- Muhammad Azfal, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05716516
- Sponsor's protocol ID
- STUDY02001740
- Other IDs
- NCI-2023-05453
- Acronym
- ESTHER
- Status last verified
- Apr 2026
- First submitted
- 28 Jan 2023
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Estradiol Therapy to Target ER-Mutant and ER-Wild-Type ER+ Metastatic or Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT05716516
- Acronym / sponsor ID
- ESTHER / STUDY02001740
- Conditions
- Metastatic Breast Cancer
- Keywords
- Metastatic, Locally advanced, Estradiol therapy, Estrogen therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- 4 May 2023 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 8 Feb 2023 (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.
Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher rate of clinical benefit from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer
Detailed description
Patients with endocrine-resistant breast cancer are eligible. Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined. Observational Phase (optional): After disease progression on 17b-estradiol, patients will be treated at their oncologist's discretion. Clinical benefit, progression-free survival, and objective response will be measured during this line of treatment of physician's choice until another instance of disease progression. In consented subjects who undergo a clinically indicated tumor biopsy of recurrent or metastatic disease prior to the start of 17b-estradiol treatment, when feasible, acquisition of additional tumor tissue is requested for research purposes. Optional: patients will be asked to provide tumor tissue via a research biopsy on Day 3-4 of 17b-estradiol treatment. Archived tumor tissue and clinical-grade tumor and plasma DNA/RNA sequencing results will be used for research purposes. Blood samples will be obtained at baseline, on Day 3-4 of 17b-estradiol therapy (optional), and upon disease progression on 17b-estradiol. Plasma and buffy coat will be extracted and frozen. Tumor tissue and plasma specimens will be analyzed to identify molecular biomarkers predictive of sensitivity/resistance to 17b-estradiol therapy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Other | Drug: EstradiolTreatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Post-menopausal women with ER+ breast cancer.
- Metastatic or locoregional recurrence not amenable to treatment with curative
- intent.
- Received ≥1 prior line of endocrine-based therapy (e.g., including tamoxifen, aromatase inhibitors, fulvestrant, or combinations) in the advanced/metastatic setting
Key exclusion criteria (12 listed)
- During the study Treatment Phase with 17b-estradiol, no concurrent anti-cancer therapies are allowed with the following exceptions:
- Any investigational cancer therapy in the last 3 weeks.
- Known CNS disease, unless clinically stable for ≥ 3 months.
- History of any of the following:
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 |
|---|---|---|
| EstradiolAlso: EstraceEstradiol is a therapeutic option for the treatment of advanced ER+ breast cancer | Drug | Treatment Arm |
Primary outcome
Clinical Benefit Rate
Time frame: 12 months
The clinical benefit rate (complete responses + partial responses + stable disease at 24 weeks) will be ascertained and compared between subjects treated with 17b-estradiol harboring amplified/mutant ESR1 and wild-type ESR1.
4 secondary outcomes
Objective response rate
Time frame: 8 weeks
Progression-free survival
Time frame: 12 months
Tumor Metabolic response
Time frame: 12 months
Adverse event profiles
Time frame: 12 months
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 May 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.
Muhammad Azfal, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Estradiol in people with Metastatic Breast Cancer, run by Dartmouth-Hitchcock Medical Center 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 4 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 5 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Research Nurse (1-800-639-6918, Cancer.Research.Nurse@dartmouth.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Benefit Rate (time frame: 12 months). 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 May 2026.