Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03941730|
Recruitment Status : Recruiting
First Posted : May 8, 2019
Last Update Posted : August 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IIIA Breast Cancer AJCC v8 Anatomic Stage IIIB Breast Cancer AJCC v8 Anatomic Stage IIIC Breast Cancer AJCC v8 Anatomic Stage IV Breast Cancer AJCC v8 ESR2 Positive Estrogen Receptor Negative HER2/Neu Negative Metastatic Triple-Negative Breast Carcinoma Progesterone Receptor Negative Prognostic Stage III Breast Cancer AJCC v8 Prognostic Stage IIIA Breast Cancer AJCC v8 Prognostic Stage IIIB Breast Cancer AJCC v8 Prognostic Stage IIIC Breast Cancer AJCC v8 Prognostic Stage IV Breast Cancer AJCC v8 Recurrent Breast Carcinoma||Biological: Therapeutic Estradiol||Phase 2|
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.
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.
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).
Patients receive estradiol orally (PO) thrice daily (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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Therapeutic Targeting of ER Beta in Triple Negative Breast Cancer|
|Actual Study Start Date :||August 28, 2019|
|Estimated Primary Completion Date :||April 30, 2022|
|Estimated Study Completion Date :||April 30, 2022|
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
- Clinical benefit rate [ Time Frame: 6 months ]Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria 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.
- Incidence of adverse events [ Time Frame: 5 years ]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.
- Tumor response rate [ Time Frame: 5 years ]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.
- Progression free survival (PFS) distribution [ Time Frame: From randomization to the first of the following events: local, regional, or distant recurrence, second primary disease of death due to any cause, assessed up to 5 years ]The distribution of PFS times will be estimated using the method of Kaplan-Meier.
- Overall survival distribution [ Time Frame: From randomization to death due to any cause, assessed up to 5 years ]The distribution of survival times are estimated using the method of Kaplan-Meier.
- Changes in phospho-ERbeta, cystatins 1, 2, 4 and 5, phospho-Smad2/3 and Ki-67 [ Time Frame: 5 years ]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).
- Changes in serum cystatin levels in response to treatment [ Time Frame: 3 years ]Change in cystatin levels following one cycle of treatment are examined using signed rank tests and the difference in the percent change in its level following one cycle of treatment between patients who derived clinical benefit and those who did not will be examined using a two sample Wilcoxon rank sum test.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03941730
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Matthew P. Goetz|
|Principal Investigator:||Matthew P Goetz||Mayo Clinic|