Safety and Efficacy of Exemestane Plus Dasatinib Versus Placebo for Advanced ER+ Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Exemestane + Dasatinib; Exemestane + Placebo
Intervention description: Tablets, Oral, Exemestane 25 mg + Dasatinib 100 mg, once daily, until disease progression or unacceptable toxicity; Tablets, Oral, Exemestane 25 mg + Placebo 100 mg, once daily, until disease progression or unacceptable toxicity
Intervention MeSH terms: Dasatinib; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 155.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Estrogen Receptor Positive Breast Cancer

Summary:

      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).
    

Eligibility criteria:

        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