Correlate BRCA1 Protein Expression With Response to DNA Damaging Chemotherapy

Study Overview
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Brief Summary
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Primary Objective: To evaluate if low BRCA1 protein expression has a preferential effect on response when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls Secondary Objective: To evaluate if low BRCA1 protein expression has a preferential effect on tumor progression when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls

Detailed Description
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DNA is constantly subject to damage from exposures including drugs (including chemotherapy), sunlight and aging. Certain genes in the human body help repair this damage (i.e. BRCA1 and other genes). The purpose of this study is to find out if BRCA1 protein expression has a role in response to chemotherapy drugs.

Official Title
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A Single Arm Phase II Trial to Assess Association of BRCA1 Protein Expression With Overall Response Rate in Patients With Metastatic Breast Cancer on Pegylated Liposomal Doxorubicin

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Pegylated liposomal doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic breast cancer and have formalin-fixed, paraffin embedded primary tumor available for testing BRCA1 protein expression Adults over 18 years of age Have resolution of all acute toxic effects of any prior chemotherapy or radiotherapy to NCI CTC grade ≤ 1 prior to study registration. Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures Be willing and able to comply with the treatment plan, scheduled clinic visits, laboratory and oncological tests and other study procedures Have a ECOG performance status of 0 - 2 Measurable disease by CT by RECIST 1.1 to evaluate response Adequate bone marrow function defined as platelets 100 X 109 cells/L, neutrophils 1.5 x 109 cells/L, white blood cells (WBC) 3.0 x 109 cells/L and a hemoglobin 90 gm/L Creatinine < 1.5 mg/dl or creatinine clearance > 40 ml/min Liver function tests (AST and or ALT) should be 2 x upper limit of normal (ULN, defined as per laboratory where blood testing is done), total bilirubin 1.5 x ULN (except for patients with liver metastases, ALT and/or ALT 5 times the upper limit of normal is accepted) Exclusion Criteria: Myocardial infarction within 6 months of registration Brain metastases unless documented to be controlled post completion of local therapy (surgery and/or radiation therapy) for at least four weeks prior to registration Pregnant or breast feeding women. Women with child bearing potential must use effective measures to prevent pregnancy while receiving pegylated liposomal doxorubicin Have a concurrent active non-breast malignancy except for non-melanoma skin cancer Her2 positive tumors as defined by FDA guidelines(3+ immunohistochemical staining, defined as uniform, intense membrane staining of more than 10% of invasive tumor cells, and for cases with 2+ staining showing gene amplification by FISH, expressed as a ratio of more than 2 when comparing HER-2 gene and chromosome 17 fluorescent signals)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Pegylated liposomal doxorubicin<br>The enrolled patients will be treated with pegylated liposomal doxorubicin at 30mg/m2 every 21 days. | Drug: Pegylated liposomal doxorubicin<br>* Doxil will be administered intravenously at 30mg/m2 on days 1 of a 21 day cycle.<br>* Other names: Doxil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate for Metastatic Breast Cancer Patients With Low BRCA1 Protein Expression in Their Tumor, Treated With Pegylated Liposomal Doxorubicin | Evaluating if low BRCA1 protein expression has a preferential effect on response when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls. Response rate is defined as the percentage of evaluable patients who achieve complete response (CR) or partial response (PR) as measured by RECIST 1.1 on CT or PET/CT as the best overall response. | Start of treatment and repeat imaging done at 9 weeks (± 7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival for Patients With Breast Cancer With Low BRCA1 Protein Expression Treated With Pegylated Liposomal Doxorubicin | Evaluating if low BRCA1 protein expression has a preferential effect on tumor progression when metastatic breast cancer patients are treated with DNA damaging chemotherapy agent, compared to historical controls. Progression free survival will be measured as the times from the start of pegylated liposomal doxorubicin to the time the patient is first recorded as having disease progression or dies. If a patient does not progress or die while being followed via tumor assessment, progression-free survival will be censored at the time of last disease assessment. The median progression free survival will be calculated in patients with low BRCA1 protein expression and intact BRCA1 protein expression. Median progression free survival will be estimated by Kaplan-Meier methodology | Start of Treatment until the date of first documented progression or date of death, assessed up to an expected average of 100 weeks |