Evaluation of the Use of AZD6244 to Induce Increased ER Expression and Anti-Estrogen Response in ER-Negative/Low Breast Cancer

Study Overview
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Brief Summary
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If AZD6244 is able to increase ER expression in ER-negative/low cancers then it may be possible to effectively use hormonal therapy in these patients resulting in improved outcomes. The investigators propose a single-arm Simon two-step study to examine whether treatment with AZD6244 will result in increased ER expression in ER-negative/low primary breast tumors.

Official Title
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Evaluation of the Use of AZD6244 to Induce Increased ER Expression and Anti-Estrogen Response in ER-Negative/Low Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: AZ6244


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female breast cancer patient > 18 years. Patients must have biopsy-proven clinical Stage Ic-III invasive breast carcinoma with ≤ 10% ER expression by immunohistochemistry (IHC) analysis. Patients must have a pre-treatment baseline core biopsy or incisional biopsy available for additional testing (ER, protein/gene expression analysis). Patients must have sufficient tumor remaining following diagnostic biopsy that requires an additional definitive surgical procedure per the standard of care. Planned procedure may include lumpectomy or mastectomy as clinically indicated. Patients must have an ECOG Performance Status of 0 - 1. Patients must have the ability to understand and willingness to sign an English or a Spanish language written informed consent document. Exclusion Criteria: Male breast cancer patient. Patients who are pregnant or breast-feeding are excluded from the study due to potential harm to the fetus or nursing infant from the study therapy. Patients of reproductive potential must consent to use of contraception or abstinence to be eligible for the study. Patients may not have received prior chemotherapy or hormonal therapy for treatment of the current breast cancer. Patients should not have known or strongly suspected BRCA mutation by history (genetic testing not required). Patients will have pre-study testing, including history and physical exam, complete blood count, and measurement of renal and hepatic function. Patients will be ineligible for the study if significant abnormalities are detected, in accordance with good medical practice.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD6244<br> | Drug: AZ6244<br>* AZD6244 75 mg (3 x 25mg capsules) orally twice per day on Days 1 - 15<br>* Other names: AZD6244;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase of ER Protein Expression in ER-Negative/Low Breast Cancer | To evaluate in a clinical neoadjuvant model whether MEK inhibitor AZD6244 can increase ER protein expression in ER-negative/low breast cancer, as measured by the ER response rate by both standard immunohistochemistry and Allred Score. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ER-regulated Gene Expression in E-negative/Low Breast Cancer | To assess for changes in ER-regulated gene expression in ER-negative/low breast tumors following AZD6244 therapy through assessment of protein expression by immunhistochemistry in paraffin embedded tissues. | 2 Years | 
| Rate of ER Promoter Methylation in ER-negative/Low Breast Cancer | To determine the rate of ER promoter methylation in ER-negative/low breast cancer tumors that do not attain an ER response following AZD6244 therapy. | 2 years | 
| In Vitro Tamoxifen Response in Tumors | To assess for in vitro tamoxifen response in tumors following therapy with AZD6244. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, ER-negative, Allred Score