Dasatinib in Combination With Zoledronic Acid for the Treatment of Breast Cancer With Bone Metastasis

Inclusion Criteria

• Patients must have a pathologically confirmed diagnosis of invasive carcinoma of the breast.
• Patients must carry a diagnosis of metastatic breast cancer with predominant bone involvement. For the purposes of this study, predominant bone involvement will be defined as radiographically detected bone metastasis in the presence or absence of other sites of metastatic breast cancer (i.e. visceral involvement). If visceral involvement is present, patients must be asymptomatic and have no tumors in visceral organs that measure >3cm in size.
• Patients must agree to serial urine collections for measurement of Ntx.
• Age >/= 18 years.
• Patients must be able to swallow oral medications. Dasatinib must be taken whole and cannot be crushed.
• Patients must have evaluable disease using WHO Criteria for Assessment of Disease Response in Bone or MDACC Modified Response Criteria for Assessment of Disease Response in Bone.
• Patients must not have had >1 chemotherapy regimens for metastatic disease. Patients with metastasis diagnosed /= 1,500/mcL, Platelet count >/= 100,000/mcL, Bilirubin /= Lower Limit of Normal (LLN) [subjects with low electrolyte levels must be repleted to normal for protocol entry]
• Patients must not receive any concurrent bisphosphonate therapy other than that prescribed by the study.
• Sexually active patients with reproductive potential must agree to use an effective method of birth control during the course of the study and for no less than 4 weeks after discontinuing study drug. Contraceptives must be used in a manner such that risk of failure is minimized. Oral contraceptives should be avoided in women with estrogen or progesterone receptor positive breast cancer.
• Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
• All WOCBP MUST have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study.
• Patients with disease progression while receiving previous therapy in combination with bisphosphonates (including zoledronic acid) will be considered eligible for protocol participation.

Exclusion Criteria

• Any malignancy (other than breast cancer) that required radiotherapy or systemic treatment within the past 5 years.
• Concurrent medical condition which may increase the risk of toxicity, including: Pleural or pericardial effusion of any grade, clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand's disease)
• Cardiac Symptoms, including the following: Uncontrolled angina, congestive heart failure or MI within (6 months), diagnosed congenital long QT syndrome, any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), prolonged QTc interval on pre-entry electrocardiogram (> normal range), subjects with hypokalemia or hypomagnesemia if it cannot be corrected
• History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), ongoing or recent ( /= 12.0 mg/dL (3.0 mmol/L) at Visit 1. The formula to be used is: Corrected serum calcium (mg/dL) = Patient's serum calcium (mg/dL) + [0.8 x Midrange Albumin (g/dL) - Patient's Albumin (g/dL)]. 4.0g/dL to be used for the Midrange Albumin
• Serum creatinine greater than or equal to 1.5 times the institutional upper limits of norm