Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer

A Randomized, Double-Blind, Multi-Center Phase II Trial of Exemestane (Aromasin®) Plus Dasatinib Versus Exemestane Plus Placebo in Advanced Estrogen Receptor-Positive Breast Cancer After Disease Progression on a Non-Steroidal Aromatase Inhibitor (NSAI)

The purpose of this study is to determine whether exemestane plus dasatinib will be well-tolerated and will increase progression-free survival (PFS) in the treatment of advanced estrogen-receptor positive (ER+) breast cancer after disease progression (PD) on a non-steroidal aromatase inhibitor (NSAI).

Inclusion Criteria:

• Histologically-documented invasive estrogen receptor positive breast cancer , with tumor tissue from prior surgery available for analysis
• Prior therapy with a non-steroidal aromatase inhibitor
• Recurrent or progressive advanced breast cancer (locally-advanced or metastatic)
• Documented breast cancer with tumor ≤ 28 days prior to study entry
• Women who are NOT of childbearing potential
• Must be able to take oral medication
• Performance Status 0 or 1

Exclusion Criteria:

• Pleural or pericardial effusion or ascites (of any etiology; Grade ≥ 1) within 6 months prior to study entry
• Any chemotherapy, immunotherapy < 6 months before study entry. Any targeted therapy (eg. lapatinib) < 6 months before study entry, unless given in combination with an NSAI
• Any antitumor therapy, including radiotherapy or hormonal therapy, within 15 days prior to study entry
• Prior exposure to exemestane, any Src-family kinase inhibitor including dasatinib, to agents intended to control osteolytic disease other than bisphosphonates, or to any investigational agent for breast cancer
• Concurrent or previous malignant disease requiring chemotherapy or radiation treatment within the prior 3 years
• Significant bleeding disorder, or ongoing or recent clinically-significant gastrointestinal bleeding
• Any serious cardiac condition, including congestive heart failure or myocardial infarction within 6 months, uncontrolled angina, or Class III or IV heart disease as defined by the New York Heart Association, baseline ejection fraction ≤ 40%, diagnosed congenital long QT syndrome, clinically-significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes), QTc interval > 450 msec at baseline (Fridericia correction)
• Hematologic abnormality Grade ≥ 2
• Hypocalcemia of Grade ≥ 1
• Any Chemistry abnormality of Grade ≥ 2 [except Grade 2 indirect bilirubin permitted if diagnosed Gilbert's disease]
• Pregnant Women and Women of Childbearing Potential (WOCBP)
• Extremely lactose intolerant, in the judgment of treating physician (100 mg dasatinib contains 135 mg lactose, posing a problem only if intolerance is severe)
• Receiving any of the following concomitant medications: Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Subjects must discontinue drug use at least 7 days prior to starting dasatinib)
• Potent inhibitors of CYP3A4 isoenzyme
• Prisoners or subjects who are involuntarily incarcerated; or subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness