- Solid Tumors
- Pipeline Molecules
- Alliance Partners
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Currently, you can access the following clinical trials being conducted worldwide:
Clinicaltrials.gov identifier NCT03941730
Recruitment Status Recruiting
First Posted May 8, 2019
Last update posted October 1, 2020
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.
PRIMARY OBJECTIVE: I. 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) and who have prior receipt of taxane and anthracycline based chemotherapy. SECONDARY OBJECTIVES: I. 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: I. 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). 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. After completion of study treatment, patients are followed up annually for 5 years from study registration.
|Experimental: Treatment (estradiol)
Patients receive estradiol PO TID for days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Therapeutic Estradiol
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, , Learn About Clinical Studies.-->
- PRE-SCREENING CRITERIA (STEP 0): History of locally advanced or metastatic breast
cancer that is ERalpha negative or low (< 10% nuclear staining) and HER2 negative. - Note: HER2 negative disease per 2013 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 not amplified by ISH or; - IHC not done and not amplified by ISH. - PRE-SCREENING CRITERIA (STEP 0): = 25% of cells in specimen submitted during Pre-Screening Step.
- PRE-REGISTRATION CRITERIA (STEP 1): 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.
- Note: The tumor lesion biopsied during the pre-registration period is not
considered measurable disease.
- PRE-REGISTRATION CRITERIA (STEP 1): If history of brain metastases must meet the
- 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): Prior treatment with paclitaxel and anthracycline (in combination or in separate regimens) either in the adjuvant or metastatic setting, - PRE-REGISTRATION CRITERIA (STEP 1): == 60 years, or
- Age 1 year with follicle stimulating hormone
(FSH) and estradiol levels within postmenopausal range, according to
- 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): Histologic confirmation, from local lab that tumor is
ERalpha negative (= 8 g/dL (== 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 = 160/90).
- PRE-REGISTRATION CRITERIA: Deep vein thrombosis / pulmonary embolism (DVT/PE) = 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 CRITERIA: Abnormal uterine bleeding == 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).
United States, Florida
Mayo Clinic in Florida
United States, Minnesota
National Cancer Institute (NCI)
Principal Investigator: Matthew P Goetz Mayo Clinic