Apply to Trial

Compensation: Varies

Number of Visits: 1

Duration: 6 months

5 Participants Needed

Therapeutic Estradiol for Breast Cancer

Recruiting at 13 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy, Immunotherapy, Hormonal, others

Disqualifiers: Uncontrolled hypertension, Stroke, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Prior Safety DataThis treatment has passed at least one previous human trial

Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using strong inducers or inhibitors of CYP3A4 before registration. Additionally, no chemotherapy, immunotherapy, biologic therapy, hormonal therapy, monoclonal antibodies, or targeted therapies are allowed within 14 days prior to registration.

Is estradiol generally safe for use in humans?

Estradiol, used in various hormone therapies, has been associated with some common side effects like weight gain, headache, and nausea, but serious adverse events are rare. Safety data from similar hormone therapies suggest that when used as directed, estradiol is generally safe, though monitoring is recommended to manage any potential risks.¹ ² ³ ⁴ ⁵

How does the drug Estradiol differ from other breast cancer treatments?

Estradiol is unique because it is a form of estrogen, which is typically not used in breast cancer treatment due to concerns about stimulating cancer growth. However, in certain cases, it can be used to treat hormone-sensitive breast cancer by exploiting the cancer cells' dependence on estrogen, potentially leading to their death when exposed to high levels of the hormone.⁶ ⁷ ⁸ ⁹ ¹⁰

What is the purpose of this trial?

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.

Research Team

Matthew P. Goetz

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for postmenopausal women with a specific breast cancer type that's spread within the body or to nearby areas. Participants must have ER beta positive, triple negative tumors and be in good general health (ECOG status 0 or 1). They should not have had more than three prior chemo treatments for metastatic breast cancer and must agree to undergo necessary biopsies.

Inclusion Criteria

My cancer's size or presence can be tracked with scans.

Your hemoglobin level should be at least 8 grams per deciliter within 14 days before joining the study.

I have gone through menopause.

See 15 more

Exclusion Criteria

I have a history of blood clotting disorders.

I have had 2 or more blood clots in the last 5 years.

I have not had a blood clot in my veins or lungs in the last year.

See 5 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive estradiol orally three times daily for 28-day cycles, with biopsies and blood samples collected at specified intervals

6 months

Biopsies at end of cycle 1, blood samples on day 1 of cycle 1, end of cycle 1, and end of treatment; imaging at baseline, end of cycles 2, 4, and 6, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Annual follow-up visits

Treatment Details

Interventions

Estradiol

Trial Overview The study tests how effective estradiol, a form of estrogen, is on patients whose tumor cells overexpress ER beta but lack other hormone receptors. The goal is to see if estradiol can shrink these specific types of tumor cells. Various imaging techniques like CT scans will monitor the results.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Treatment (estradiol)Experimental Treatment5 Interventions

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.

Estradiol is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Estradiol for:

Menopausal symptoms
Hypoestrogenism
Osteoporosis prevention
Breast cancer palliation
Prostate cancer palliation

Approved in United States as Estradiol for:

Moderate to severe vasomotor symptoms due to menopause
Vulvar and vaginal atrophy due to menopause
Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
Prevention of postmenopausal osteoporosis
Palliative treatment of breast cancer
Palliative treatment of prostate cancer

Approved in Canada as Estradiol for:

Menopausal symptoms
Hypoestrogenism
Osteoporosis prevention
Breast cancer palliation
Prostate cancer palliation

Find a Clinic Near You

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Tamoxifen effectively reduces the risk of estrogen receptor-positive breast cancer by at least 50% in both pre- and postmenopausal women, highlighting its efficacy as a preventive treatment.

Newer agents like aromatase inhibitors have shown even greater reductions in breast cancer risk (up to 65% with exemestane and 60% with anastrozole) for postmenopausal women, but there is a need for more targeted therapies for premenopausal women with estrogen receptor-negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventative therapies for healthy women at high risk of breast cancer.Sestak, I.[2020]

Selective estrogen receptor modulators (SERMs) and antiestrogens, such as raloxifene and bazedoxifene, are safe options for postmenopausal women as they do not increase breast cancer risk and may even offer protection against it.

The combination of conjugated estrogens with bazedoxifene has shown an improved breast safety profile compared to traditional hormone therapies, with no increase in breast density or pain over two years, indicating a safer alternative for managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast.Pickar, JH., Komm, BS.[2018]

A comprehensive safety review of Estratest and Estratest HS, based on over 1 million woman-years of exposure from 1989 to 1996, found no significant safety concerns, with only 863 adverse events reported, which is relatively low given the extensive use.

The most common adverse events were typical of estrogen and androgen therapies, such as weight gain and headaches, and serious adverse events were rare, indicating that these medications are safe when used as directed, with manageable risks associated with their androgen component.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States.Phillips, E., Bauman, C.[2019]