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

This is an interventional treatment trial for Estrogen Receptor-negative Breast Cancer Read More

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