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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01313039
• Other study ID #: UMIAMI-20100252
• Status: Completed
• Phase: Phase 0
• First received: March 9, 2011
• Last updated: July 25, 2014
• Start date: February 2011
• Est. completion date: April 2014

Study information

• Verified date: May 2014
• Source: University of Miami Sylvester Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• AZ6244
AZD6244 75 mg (3 x 25mg capsules) orally twice per day on Days 1 - 15

Locations

Country	Name	City	State
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Miami Sylvester Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	2 years	No
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.	2 Years	No
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.	2 years	No
Secondary	In Vitro Tamoxifen Response in Tumors	To assess for in vitro tamoxifen response in tumors following therapy with AZD6244.	2 years	No