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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: AZ6244

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Study Chair: Judith Hurley, MD, University of Miami Sylvester Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: March 9, 2011
• First Submitted That Met QC Criteria: March 10, 2011
• First Posted (Estimate): March 11, 2011

Study Record Updates

• Last Update Posted (Estimate): February 7, 2017
• Last Update Submitted That Met QC Criteria: December 14, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Breast Cancer; ER-negative; Allred Score
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 20100252

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No