Condition or disease | Intervention/treatment | Phase |
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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 Metastatic Triple-Negative Breast Carcinoma 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 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 38 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Arm | Intervention/treatment |
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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.
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Biological: Therapeutic Estradiol
Given PO
Other Names:
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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:
PRE-SCREENING CRITERIA (STEP 0): =< 2 prior chemotherapy regimens for treatment of metastatic breast cancer.
PRE-REGISTRATION CRITERIA (STEP 1): Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
PRE-REGISTRATION CRITERIA (STEP 1): If history of brain metastases must meet the following criteria:
PRE-REGISTRATION CRITERIA (STEP 1): Women must be postmenopausal.
NOTE: Postmenopausal status is verified by:
PRE-REGISTRATION CRITERIA (STEP 1): Willingness to stop use of strong inducers or inhibitors of CYP3A4 prior to registration.
REGISTRATION CRITERIA (STEP 2): Histologic confirmation, from local lab that tumor is ERalpha negative (< 1% nuclear staining), and HER2 negative.
Note: HER2 negative disease per 2013 ASCO/CAP guidelines, one of the following must apply:
REGISTRATION CRITERIA (STEP 2): Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) 2.5 x ULN (=< 14 days prior to registration).
Exclusion Criteria:
PRE-REGISTRATION CRITERIA: Uncontrolled intercurrent illness including, but not limited to:
PRE-REGISTRATION CRITERIA: Deep vein thrombosis / pulmonary embolism (DVT/PE) =< 12 months prior to pre-registration.
PRE-REGISTRATION CRITERIA: Other active second malignancy other than non-melanoma skin cancers within 3 years prior to pre-registration.
REGISTRATION CRITERIA: None of the following therapies are allowed =< 14 days prior to registration.
United States, Florida | |
Mayo Clinic in Florida | Recruiting |
Jacksonville, Florida, United States, 32224-9980 | |
Contact: Clinical Trials Referral Office 855-776-0015 mayocliniccancerstudies@mayo.edu | |
Principal Investigator: Alvaro Moreno-Aspitia | |
United States, Minnesota | |
Mayo Clinic | Recruiting |
Rochester, Minnesota, United States, 55905 | |
Contact: Clinical Trials Referral Office 855-776-0015 mayocliniccancerstudies@mayo.edu | |
Principal Investigator: Matthew P. Goetz |
Principal Investigator: | Matthew P Goetz | Mayo Clinic |
Tracking Information | |||||
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First Submitted Date ICMJE | May 6, 2019 | ||||
First Posted Date ICMJE | May 8, 2019 | ||||
Last Update Posted Date | October 1, 2020 | ||||
Actual Study Start Date ICMJE | August 28, 2019 | ||||
Estimated Primary Completion Date | April 30, 2022 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
Changes in serum cystatin levels in response to treatment [ Time Frame: At the end of Cycle 1 (each cycle is 28 days +/- 3 days) ] 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.
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Original Other Pre-specified Outcome Measures |
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.
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Descriptive Information | |||||
Brief Title ICMJE | Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer | ||||
Official Title ICMJE | Therapeutic Targeting of ER Beta in Triple Negative Breast Cancer | ||||
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. | ||||
Detailed Description |
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. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Biological: Therapeutic Estradiol
Given PO
Other Names:
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Study Arms ICMJE | 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.
Intervention: Biological: Therapeutic Estradiol
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
38 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | April 30, 2022 | ||||
Estimated Primary Completion Date | April 30, 2022 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | |||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03941730 | ||||
Other Study ID Numbers ICMJE | MC1831 NCI-2019-02285 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MC1831 ( Other Identifier: Mayo Clinic ) P30CA015083 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | Mayo Clinic | ||||
Study Sponsor ICMJE | Mayo Clinic | ||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||
Investigators ICMJE |
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PRS Account | Mayo Clinic | ||||
Verification Date | April 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |