Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery

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