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

NCT03941730 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 6 other identifiers: MC1831P50CA116201R01CA249116NCI-2019-0228518-000734TBCRC051
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 9

Brief 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). 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.

Conditions

Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Recurrent Breast Carcinoma; Advanced Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (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.

  173 days

Secondary Outcomes (5)

• Incidence of Adverse Events

  5 years

• Tumor Response Rate Among Those Patients With Measurable Disease

  173 days

• Progression Free Survival (PFS) Distribution

  173 days

• Overall Survival (OS) Distribution

  18 months

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

  5 years

Other Outcomes (1)

• Changes in Serum Cystatin Levels in Response to Treatment

  Baseline up to cycle 1

Study Arms (1)

Treatment (estradiol)

EXPERIMENTAL

Patients 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.

Procedure: Biopsy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Therapeutic Estradiol

Interventions

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (estradiol)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (estradiol)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (estradiol)

Therapeutic Estradiol BIOLOGICAL

Given PO

Also known as: 17 Beta-Estradiol, Aquadiol, Climara, Dimenformon, Diogyn, Diogynets, Estrace, ESTRADIOL, Estraldine, Oestradiol, Ovocylin, Progynon, Vagifem

Treatment (estradiol)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (estradiol)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• or 1+ by immunohistochemistry (IHC) and not amplified by in situ hybridization (ISH);
• or 1+ by IHC and ISH not done;
• + by IHC and ISH results are: \< 6.0 HER2 signals/cell with HER2/CEP17 ratio \< 2.0;
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

FHCC South Lake Union

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

Biopsy; Magnetic Resonance Spectroscopy; Estradiol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Matthew Goetz
• Organization: Mayo Clinic

goetz.matthew@mayo.edu

507-293-0526

Study Officials

• Matthew P. Goetz, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 8, 2019
• Study Start: August 28, 2019
• Primary Completion: July 29, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 5, 2026
• Results First Posted: March 5, 2026

Record last verified: 2026-03

Locations

US (9)