Correlate BRCA1 Protein Expression With Response to DNA Damaging Chemotherapy

Phase 2

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Pegylated liposomal doxorubicin	Pegylated liposomal doxorubicin	The enrolled patients will be treated with pegylated liposomal doxorubicin at 30mg/m2 every 21 days.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate for Metastatic Breast Cancer Patients With Low BRCA1 Protein Expression in Their Tumor, Treated With Pegylated Liposomal Doxorubicin	Start of treatment and repeat imaging done at 9 weeks (± 7 days)	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival for Patients With Breast Cancer With Low BRCA1 Protein Expression Treated With Pegylated Liposomal Doxorubicin	Start of Treatment until the date of first documented progression or date of death, assessed up to an expected average of 100 weeks	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

Locations (2): University of Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
University of New Mexico Comprehensive Cancer Center
🇺🇸
Albuquerque, New Mexico, United States