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Advanced Triple-Negative Breast CarcinomaPhase 2NCT03941730

Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer

A Phase 2 study testing Biopsy, Computed Tomography and Magnetic Resonance Imaging in people with Advanced Triple-Negative Breast Carcinoma and Anatomic Stage III Breast Cancer AJCC v8, run by Mayo Clinic at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase II trial studies how well estradiol works in treating patients with estrogen receptor beta (ER beta) positive, triple negative breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Biopsy, Computed Tomography and Magnetic Resonance Imaging
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
9 sitesUnited States
Study dates
28 Aug 2019to 31 Dec 2026
Phase
Phase 2
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 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PRE-SCREENING CRITERIA (STEP 0): Women of age >= 18 years
  • PRE-SCREENING CRITERIA (STEP 0): History of locally advanced or metastatic breast cancer that is ERalpha negative or low (< 1% nuclear staining) and HER2 negative.
  • Note: HER2 negative disease per 2018 American Society of Clinical Oncology/College of American of Pathologists (ASCO/CAP) guidelines, one of the following must apply:
  • 0 or 1+ by immunohistochemistry (IHC) and not amplified by in situ hybridization (ISH);
  • 0 or 1+ by IHC and ISH not done;
  • 2+ by IHC and ISH results are: < 6.0 HER2 signals/cell with HER2/CEP17 ratio < 2.0;
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  • IHC not done and not amplified by ISH.
  • PRE-SCREENING CRITERIA (STEP 0): =< 3 prior chemotherapy regimens for treatment of metastatic breast cancer.
  • Note: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed (if administered as monotherapy it is not counted as a chemotherapy regimen).
  • PRE-SCREENING CRITERIA (STEP 0): Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • PRE-SCREENING CRITERIA (STEP 0): Willing to submit a biopsy specimen from locally recurrent or metastatic site (or primary if metastatic site not available) of breast cancer for ERbeta staining to Mayo Clinic Anatomic Pathology.
  • PRE-SCREENING CRITERIA (STEP 0): No prior history of metastatic ERalpha positive breast cancer (>= 1%)
  • PRE-REGISTRATION CRITERIA (STEP 1): Presence of moderate or strong nuclear ERbeta staining in > 25% of cells in specimen submitted during Pre-Screening Step.
  • PRE-REGISTRATION CRITERIA (STEP 1): For patients who did not have a biopsy or lacking ERalpha, progesterone receptor (PR), and HER2 results from a locally advanced or metastatic site performed =< 12 months prior to Pre-Registration: Willing to undergo a standard of care biopsy of locally recurrent or metastatic breast cancer for ERalpha, PR, and HER2 as well as additional research cores.
  • PRE-REGISTRATION CRITERIA (STEP 1): Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria that will be assessed using imaging-based evaluations.
  • Note: The tumor lesion biopsied during the pre-registration period is not considered measurable disease nor a target lesion.
  • PRE-REGISTRATION CRITERIA (STEP 1): If history of brain metastases must meet the following criteria:
  • Patients with a history of brain metastases are eligible only if they are asymptomatic and have stable disease for >= 3 months, including < 28 days of prior to pre-registration.
  • Not receiving steroids for brain metastases.
  • PRE-REGISTRATION CRITERIA (STEP 1): ECOG performance status 0 or 1.
  • PRE-REGISTRATION CRITERIA (STEP 1): =< 3 prior chemotherapy regimens for treatment of metastatic breast cancer.
  • NOTE: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed.
  • PRE-REGISTRATION CRITERIA (STEP 1): Women must be postmenopausal.
  • NOTE: Postmenopausal status is verified by:
  • Prior bilateral surgical oophorectomy, or
  • Age >= 60 years, or
  • Age < 60 years with no menses for > 1 year with estradiol levels within postmenopausal range, according to institutional standard.
  • PRE-REGISTRATION CRITERIA (STEP 1): Able to swallow oral medications.
  • PRE-REGISTRATION CRITERIA (STEP 1): Willingness to stop use of strong inducers or inhibitors of CYP3A4 prior to registration.
  • NOTE: Use of strong inducers or inhibitors is allowed during pre-registration as long as patient will complete course prior to registration.
  • REGISTRATION CRITERIA (STEP 2): For patents who had a biopsy taken from a metastatic site =< 12 months prior to Pre-Registration: Confirmation from the local lab that the tumor from this biopsy was ERalpha negative (< 1% nuclear staining) and HER2 negative
  • REGISTRATION CRITERIA (STEP 2): For patients who underwent a pre-registration biopsy: Histologic confirmation from local lab that tumor is ERalpha negative (< 1% nuclear staining), and HER2 negative
  • REGISTRATION CRITERIA (STEP 2): Hemoglobin >= 8 g/dL (=< 14 days prior to registration).
  • REGISTRATION CRITERIA (STEP 2): Platelet count >= 75,000/mm^3 (=< 14 days prior to registration).
  • REGISTRATION CRITERIA (STEP 2): Creatinine =< 1.5 x upper limit of normal (ULN) (=< 14 days prior to registration).
  • REGISTRATION CRITERIA (STEP 2): Total bilirubin =< 1.5 x ULN (=< 14 days prior to registration).
  • REGISTRATION CRITERIA (STEP 2): Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) =< 2.5 x ULN (=< 14 days prior to registration).
  • For patients with liver metastasis =< 5 x ULN.

Who cannot join

  • PRE-REGISTRATION CRITERIA: Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection.
  • Symptomatic congestive heart failure.
  • Unstable angina pectoris.
  • Uncontrolled symptomatic cardiac arrhythmia.
  • Uncontrolled hypertension (defined as blood pressure > 160/90).
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  • PRE-REGISTRATION CRITERIA: Deep vein thrombosis / pulmonary embolism (DVT/PE) =< 12 months prior to pre-registration.
  • Note: Patients who are on anticoagulant therapy for maintenance are eligible as long as the DVT and/or PE occurred > 6 months prior to pre-registration, and there is no evidence for active thrombosis (either DVT or PE).
  • PRE-REGISTRATION CRITERIA: Stroke =< 6 months prior to pre-registration.
  • PRE-REGISTRATION CRITERIA: Two or more episodes of DVT and/or PE =< 5 years prior to pre-registration.
  • PRE-REGISTRATION CRITERIA: Abnormal uterine bleeding =< 6 months prior to pre-registration
  • PRE-REGISTRATION CRITERIA: History of coagulopathy.
  • PRE-REGISTRATION CRITERIA: Other active second malignancy other than non-melanoma skin cancers within 3 years prior to pre-registration.
  • NOTE: A second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for >= 3 years prior to pre-registration.
  • REGISTRATION CRITERIA: None of the following therapies are allowed =< 14 days prior to registration.
  • Chemotherapy.
  • Immunotherapy.
  • Biologic therapy.
  • Hormonal therapy.
  • Monoclonal antibodies.
  • Anti-HER2 or other "targeted" (e.g. mTOR) therapy.
  • Note: Any adverse events derived from these therapies must be =< grade 2 prior to starting study therapy (exceptions for alopecia).

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • FHCC South Lake Union

    Seattle, Washington, 98109

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: Therapeutic Targeting of ER Beta in Triple Negative Breast Cancer

This phase II trial studies how well estradiol works in treating patients with estrogen receptor beta (ER beta) positive, triple negative breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Hormone receptors like ER beta allow the body to respond appropriately to hormones. Triple negative means that the breast cancer does not express other hormone receptors called ER alpha, progesterone, and HER2. In some people with triple negative breast cancer, ER beta is overexpressed. Tumor cells that overexpress ER beta grow slower in the laboratory and this growth is slowed in the presence of estrogen. Estradiol is a form of estrogen. This study may help doctors determine whether tumor cells that overexpress ER beta shrink in the presence of estradiol.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the anti-tumor activity of estradiol in patients with locally advanced or metastatic triple negative breast cancer (TNBC) that expresses ERbeta (> 25% moderate or strong nuclear staining).

SECONDARY OBJECTIVES:

  1. To examine the safety profile of estradiol when administered at a dose of 2 mg three times daily (TID) to women with locally advanced or metastatic TNBC that expresses ERbeta.

II. To examine the changes in phosphorylated (phospho)-ERbeta, cystatins 1, 2, 4 and 5, phospho-Smad2/3 and Ki-67 in tumor biopsies taken before and after the first cycle of treatment.

EXPLORATORY OBJECTIVES:

  1. To examine changes in plasma estradiol, serum cytokine and cystatin levels before/after 1 cycle of estradiol.

II. Analyze the global gene expression profiles of paired biopsies prior to and following 1 cycle of therapy.

III. To develop patient derived xenografts (PDX) that are ERalpha negative, HER2 negative and ERbeta positive (Mayo only).

IV. To examine changes in the relative abundance of circulating immune cell populations after the first cycle of treatment and whether these changes differ with respect to whether the patient is still on treatment after 6 cycles of treatment or not.

OUTLINE:

Patients receive estradiol orally (PO) TID for days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tissue biopsy at the end of cycle 1, collection of blood samples on day 1 of cycle 1 (C1D1), at the end of cycle 1, and at the end of treatment. In addition, patients undergo computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scans at baseline, at the end of cycles 2, 4, and 6, and then every 8 weeks until disease progression.

After completion of study treatment, patients are followed up annually for 5 years from study registration.

Being tested
Biopsy, Computed Tomography, Magnetic Resonance Imaging, Positron Emission Tomography, Therapeutic Estradiol
Medical subject headings
Triple Negative Breast Neoplasms, Breast Neoplasms

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan

    Undergo PET

  • Therapeutic EstradiolBiological

    Also called 17 Beta-Estradiol, Aquadiol, Climara, Dimenformon

    Given PO

Study groups in NCT03941730
Study groupRoleWhat they receive
Treatment (estradiol)ExperimentalPatients receive estradiol PO TID for days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tissue biopsy at the end of cycle 1, collection of blood samples on C1D1, at the end of cycle 1, and at the end of treatment. In addition, patients undergo CT, MRI, or PET scans at baseline, at the end of cycles 2, 4, and 6, and then every 8 weeks until disease progression.
Receives: Procedure: Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Therapeutic Estradiol

What is being measured

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

  1. Clinical Benefit Rate

    A patient is said to have derived clinical benefit rate at the 6 month time point if the patient's disease meets the Response Evaluation Criteria in Solid Tumors (RECIST) for complete response (CR), partial response (PR), or stable disease (SD) for > 6 months following initiation of treatment. The 6 month clinical benefit rate is the percentage of patients who are found to meet the criteria for clinical benefit at least 6 months among all the patients who have started estradiol treatment. As the number of patients with discordant ERbeta findings are expected to be small, a 90% exact binomial confidence interval will be constructed for the proportion of patients who were found to have no to weak ERβbeta expressing metastatic triple-negative breast cancer (TNBC) and who derived clinical benefit rate at the 6 month time point.

    Measured: 173 days

Secondary outcomes (5)

  1. Incidence of Adverse Events

    An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. All grade 2, 3, 4 or 5 adverse events will be documented and assigned an attribute by treating clinician as to its relationship to treatment. For a given AE, the proportion of patients who report developing a grade 2-5 of this AE are determined. The number of dose reductions per patient and the reasons for the dose reduction are summarized.

    Measured: 5 years

  2. Tumor Response Rate Among Those Patients With Measurable Disease

    The tumor response rate is defined as the 100% time the number of patients with a CR or PR (as defined by the RECIST criteria) on 2 consecutive evaluations at least 8 weeks apart divided by the total number of eligible patients who began study treatment. A 90% binomial confidence interval is constructed for the true response rate.

    Measured: 173 days

  3. Progression Free Survival (PFS) Distribution

    PFS is defined as the time from registration to the first of the following events: local, regional, or distant recurrence, second primary disease of death due to any cause. The distribution of PFS times will be estimated using the method of Kaplan-Meier.

    Measured: 173 days

  4. Overall Survival (OS) Distribution

    OS is defined as the time from registration to death due to any cause. The distribution of survival times are estimated using the method of Kaplan-Meier.

    Measured: 18 months

  5. Changes in Phospho-ERbeta, Cystatins 1, 2, 4 and 5, Phospho-Smad2/3 and Ki-67

    Patients undergo tumor biopsies prior to the start of treatment and at completion of cycle 1 treatment. These specimens will be undergoing immunohistochemistry (IHC) staining with the following antibodies: phosphorylated (phospho)-ERbeta, cystatins 1, 2, 4 and 5, phospho-Smad2/3 and Ki-67. For each of these biomarkers, a times series plot are constructed so that an individual patient's data will be represented using the same color for each of the five graphs. These graphs are visually inspected for trends within each of the graphs (variation between individuals) as well as across the five graphs (profile of biomarker changes within an individual).

    Measured: 5 years

Timeline

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

  1. First posted8 May 2019
  2. Study start28 Aug 2019
  3. Primary completion29 Jul 2024
  4. Study completion31 Dec 2026 (estimated)

Resources

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03941730
Sponsor's protocol ID
MC1831
Other IDs
P50CA116201, R01CA249116, 18-000734, TBCRC051
Status last verified
May 2026
First submitted
6 May 2019
Last updated
12 May 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Computed Tomography and Magnetic Resonance Imaging in people with Advanced Triple-Negative Breast Carcinoma and Anatomic Stage III Breast Cancer AJCC v8, run by Mayo Clinic at 9 sites 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 38 inclusion and 22 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: under way, not looking for participants, 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 9 sites 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?

Yes. Results are posted in the registry (first posted 5 Mar 2026). 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?

Clinical Benefit Rate (time frame: 173 days). 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 NCT03941730.

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.

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