Window of Opportunity Trial of Dasatinib in Operable Triple Negative Breast Cancers With nEGFR

Phase 2

Terminated

Conditions: Triple Negative Breast Neoplasms
Breast Neoplasms

Interventions: Drug: Dasatinib
Procedure: Conventional Surgery
Other: Laboratory Biomarker Analysis

Registration Number: NCT02720185

Lead Sponsor: University of Wisconsin, Madison

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:

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.

3. To examine the pathologic complete response (pCR) rates to standard neoadjuvant chemotherapy in nEGFR+ TNBC

4. To examine breast cancer recurrence rates and patterns of metastatic recurrent in nEGFR+ TNBC

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 5

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dasatinib 100mg	Conventional Surgery	Dasatinib 100mg for 7-10 days until day prior to surgery
Dasatinib 100mg	Laboratory Biomarker Analysis	Dasatinib 100mg for 7-10 days until day prior to surgery
Dasatinib 100mg	Dasatinib	Dasatinib 100mg for 7-10 days until day prior to surgery

Primary Outcome Measures

Name	Time	Method
Plasma Membrane Epidermal Growth Factor Receptor (EGFR) Expression, Measured by VECTRA Imaging	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 Outcome Measures

Name	Time	Method
Number of Treatment-emergent Adverse Events [Safety and Tolerability] up to 4 Weeks	Up to 4 weeks	Safety and tolerability of dasatinib in participants with operable Triple negative breast cancer (TNBC) will be based on NCI Adverse Events (AE) Version 4.0 and will be assessed by frequency tables. AEs were collected on day 1 of treatment and a minimum of 14 days after the last dose. AEs reported here were ranked as either possibly related, probably related, or definitely related to the study intervention. All AEs (including not related and unlikely related) are summarized in the AE section.
Number of Participants With Pathologic Complete Response (pCR)	Up to 4 weeks	Examine pCR rates to standard neoadjuvant chemotherapy in nuclear Epidermal Growth Factor Receptor (nEGFR) + TNBC. pCR will be defined as ypT0 ypNO (absence of cancer in breast tissue and lymph nodes) an assessed by the investigator.
Number of Participants With No Evidence of Disease (NED) at Long-term Follow up	up to 24 months

Trial Locations

Locations (2): University of Illinois Hospital and Health Systems (Outpatient Care Center)
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Chicago, Illinois, United States
University of Wisconsin Carbone Cancer Center
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Madison, Wisconsin, United States