Primary Objective:
To determine if dasatinib, an inhibitor of the Src family kinases, can prevent the nuclear
translocation of the epidermal growth factor receptor (EGFR) in operable, nuclear EGFR
positive, triple negative breast cancers (TNBC).
Secondary Objectives:
1. To examine the safety and tolerability of dasatinib in patients with operable TNBC
2. To explore potential intracellular mechanisms which impact dasatinib effect on cellular
localization of EGFR in operable TNBC.
Inclusion Criteria:
- nEGFR positive
- ECOG performace status 1
- Patients must have normal organ and marrow function as defined below:
- leukocytes 3,000/mcL
- absolute neutrophil count 1,500/mcL
- platelets 150,000/mcL
- total bilirubin <1.25x institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) 2.5 institutional upper limit of normal
- creatinine within normal institutional limits OR creatinine clearance 60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation and for 30 days after the final dose. Should
a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who are receiving any other investigational agents
- Patients not able to swallow oral medications or with gastrointestinal conditions
that may impact absorption of dasatinib.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dasatinib.
- Patients receiving any medications or substances that are moderate or strong
inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents
are constantly changing, medications should be reviewed by the UW Pharmacy Research
Center for any contraindicated medications. As part of the enrollment/informed
consent procedures, the patient will be counseled on the risk of interactions with
other agents, and what to do if new medications need to be prescribed or if the
patient is considering a new over-the-counter medicine or herbal product.
- H2 antagonists and proton pump inhibitors are not allowed
- Anticoagulants (ie. Coumadin, heparin, anti-Xa inhibitors) and anti-platelet agents
(ie. aspirin) are not allowed. NSAIDS and acetaminophen are allowed on study.
- Medications known to prolong QTC are not allowed (See Appendix B)
- No history of prolonged QTC or cardiomyopathy unless normal QTC and ejection fraction
confirmed within 1 month prior to study entry.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Pregnant women are excluded from this study because dasatinib is a pregnancy category
D agent with the potential for teratogenic or abortifacient effects. Because there is
an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with dasatinib, breastfeeding should be discontinued if the
mother is treated with dasatinib and not resumed until at least 2 weeks after the
final dose.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with dasatinib. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female
