Correlate BRCA1 Protein Expression With Response to DNA Damaging Chemotherapy
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Pegylated liposomal doxorubicin
Intervention description: Doxil will be administered intravenously at 30mg/m2 on days 1 of a 21 day cycle.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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)