Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery
Condition: Estrogen Receptor-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms; Breast Neoplasms, Male
Intervention: saracatinib; laboratory biomarker analysis
Intervention description: Correlative studies
Intervention MeSH terms: Saracatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying saracatinib to see how well it works in treating patients
      with metastatic or locally advanced breast cancer that cannot be removed by surgery.
      Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed carcinoma of the breast

               -  Unresectable disease

               -  Locally advanced or metastatic (American Joint Committee on Cancer [AJCC] stage
                  IV) disease

          -  Estrogen receptor-negative and progesterone receptor-negative breast cancer defined as
             < 10% expression by immunohistochemistry (IHC)

          -  Measurable disease, defined (per Response Evaluation Criteria in Solid Tumors
             [RECIST]) as ≥ 1 unidimensionally measurable lesion ≥ 20mm by conventional techniques
             or ≥ 10 mm by spiral computed tomography (CT) scan

               -  Measurable target lesions must not be in a previously irradiated field

          -  Patients with locally advanced, unresectable disease must have progression of disease
             following no more than one first-line chemotherapy regimen

          -  Patients with evidence of recurrent disease during or within 6 months after adjuvant
             chemotherapy will be considered to have failed one line of chemotherapy for metastatic
             disease

          -  Human epidermal growth factor receptor 2 (HER2)-positive patients, defined as
             immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH)
             amplification > 2.1, must have received trastuzumab (Herceptin®) in either the
             adjuvant or metastatic setting and have had recurrence or progression of disease,
             respectively

          -  No known brain metastases

          -  Male and female patients eligible

          -  Menopausal status not specified

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 (Karnofsky PS
             60-100%)

          -  Life expectancy > 3 months

          -  Absolute neutrophil count ≥ 1,500/mcL

          -  Platelet count ≥ 100,000/mcL

          -  Hemoglobin > 9 g/dL

          -  Total bilirubin normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤
             2.5 x institutional upper limit of normal

          -  Creatinine normal OR creatinine clearance ≥ 60 mL/min

          -  Urine protein creatinine (UPC) ratio must be ≤ 1.0

               -  Patients with a UPC ratio > 1.0 must have a 24-hour urine protein < 1,000 mg to
                  be eligible for study

          -  Not pregnant or nursing

          -  Women of child-bearing potential and men must use adequate contraception (e.g.,
             hormonal or barrier method of birth control or abstinence) prior to, during, and for 8
             weeks after completion of study therapy

          -  Able to understand and willing to sign a written informed consent document

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to AZD0530

          -  No QTc interval ≥ 500 msecs

          -  No condition that impairs the ability to swallow AZD0530 tablets, including the
             following:

               -  Gastrointestinal tract disease resulting in an inability to take oral medication
                  or a requirement for IV alimentation

               -  Prior surgical procedures affecting absorption

               -  Active peptic ulcer disease

          -  No intercurrent cardiac dysfunction including, but not limited to, any of the
             following:

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Uncontrolled cardiac arrhythmia

               -  History of myocardial infarction within 6 months of treatment

          -  No uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  No severe restrictive or obstructive lung disease according to baseline pulmonary
             function studies including any of the following pulmonary function test (PFT)
             parameters:

               -  Total lung capacity < 60%

               -  Forced vital capacity < 50%

               -  Forced expiratory volume in one second (FEV_1) < 50%

               -  Diffusion capacity of carbon monoxide (DLCO) < 50%

               -  Resting room air O_2 saturation < 92% or a decline in O_2 saturation > 4% with
                  exercise

          -  Patients with metastatic disease may have received no more than 1 prior chemotherapy
             regimen

          -  No unresolved toxicity ≥ grade 3 from agents received more than 3 weeks earlier

          -  No chemotherapy, radiotherapy, or investigational therapy within 3 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering study

          -  No luteinizing hormone-releasing hormone agonists within 4 weeks prior to study entry

          -  More than 7 days since prior and no concurrent use of specifically prohibited
             cytochrome P 450 3A4 (CYP3A4) agents

          -  No concurrent megestrol acetate, even when prescribed for appetite stimulation

          -  No other concurrent investigational or commercial agents for the treatment of breast
             cancer

          -  No concurrent combination antiretroviral therapy for human immunodeficiency virus
             (HIV)-positive patients

          -  No concurrent megestrol acetate