NCT02720185TerminatedPhase 2
Window of Opportunity Study of Dasatinib in Operable Triple Negative Breast Cancers With Nuclear Epidermal Growth Factor Receptor (nEGFR)
University of Wisconsin, Madison2 sites in 1 country5 target enrollmentStarted: May 3, 2017Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 5
- Locations
- 2
- Primary Endpoint
- Plasma Membrane Epidermal Growth Factor Receptor (EGFR) Expression, Measured by VECTRA Imaging
Study Overview
Brief Summary
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 Stage I-III, nuclear EGFR positive, triple negative breast cancers (TNBC).
Secondary Objectives:
- To examine the safety and tolerability of dasatinib in patients with operable TNBC
- To explore potential intracellular mechanisms which impact dasatinib effect on cellular localization of EGFR in operable TNBC.
- To examine the pathologic complete response (pCR) rates to standard neoadjuvant chemotherapy in nEGFR+ TNBC
- To examine breast cancer recurrence rates and patterns of metastatic recurrent in nEGFR+ TNBC
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
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.
- •Contraindication to repeat breast biopsy (neoadjuvant chemotherapy group)
Arms & Interventions
Dasatinib 100mg
Experimental
Dasatinib 100mg for 7-10 days until day prior to surgery
Intervention: Dasatinib (Drug)
Dasatinib 100mg
Experimental
Dasatinib 100mg for 7-10 days until day prior to surgery
Intervention: Conventional Surgery (Procedure)
Dasatinib 100mg
Experimental
Dasatinib 100mg for 7-10 days until day prior to surgery
Intervention: Laboratory Biomarker Analysis (Other)
Outcomes
Primary Outcomes
Plasma Membrane Epidermal Growth Factor Receptor (EGFR) Expression, Measured by VECTRA Imaging
Time Frame: 7-10 days
An increase of at least 25% from baseline to post-dasatinib treatment will be considered significant. VECTRA is an automated pathology imaging system used to detect biomarkers in samples.
Secondary Outcomes
- Number of Treatment-emergent Adverse Events [Safety and Tolerability] up to 4 Weeks(Up to 4 weeks)
- Number of Participants With Pathologic Complete Response (pCR)(Up to 4 weeks)
- Number of Participants With No Evidence of Disease (NED) at Long-term Follow up(up to 24 months)
Investigators
Study Sites (2)
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