Breast Cancer
Conditions
Keywords
Breast Cancer, ER-negative, Allred Score
Brief summary
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.
Interventions
DRUGAZ6244
AZD6244 75 mg (3 x 25mg capsules) orally twice per day on Days 1 - 15
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increase of ER Protein Expression in ER-Negative/Low Breast Cancer | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in ER-regulated Gene Expression in E-negative/Low Breast Cancer | 2 Years | 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. |
| Rate of ER Promoter Methylation in ER-negative/Low Breast Cancer | 2 years | 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. |
| In Vitro Tamoxifen Response in Tumors | 2 years | To assess for in vitro tamoxifen response in tumors following therapy with AZD6244. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD6244 AZ6244: AZD6244 75 mg (3 x 25mg capsules) orally twice per day on Days 1 - 15 | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | AZD6244 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 59.75 years |
| Gender Female | 4 Participants |
| Gender Male | 0 Participants |
| Region of Enrollment United States | 4 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
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.
Time frame: 2 years
Population: Only 1 subject had evaluable study data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm | Increase of ER Protein Expression in ER-Negative/Low Breast Cancer | 1 participants |
Secondary
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.
Time frame: 2 Years
Secondary
In Vitro Tamoxifen Response in Tumors
To assess for in vitro tamoxifen response in tumors following therapy with AZD6244.
Time frame: 2 years
Secondary
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.
Time frame: 2 years