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

Bristol-Myers Squibb (BMS)

Status and phase

Completed

Phase 2

Conditions

Breast Cancer

Treatments

Drug: Exemestane + Placebo

Drug: Exemestane + Dasatinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT00767520

CA180-261

Details and patient eligibility

About

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).

Enrollment

155 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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