Window of Opportunity Trial of Dasatinib in Operable Triple Negative Breast Cancers With nEGFR
Condition: Breast Neoplasms; Triple Negative Breast Neoplasms
MeSH terms: Neoplasms; Triple Negative Breast Neoplasms; Breast Neoplasms
Intervention: Dasatinib; Conventional Surgery; Laboratory Biomarker Analysis
Intervention description: 100mg oral once daily dasatinib taken for 7-10 days up to the day prior to planned surgery or research biopsy (neoadjuvant chemotherapy group); Undergo surgery; Correlative studies
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        Inclusion Criteria for nEGFR testing:

          -  Patients must have histologically or cytologically confirmed Stage I-III triple
             negative breast cancer

               -  estrogen receptor (ER) and progesterone receptor (PR) must be <1% by standard
                  assay methods

               -  human epidermal growth factor receptor-2 (HER2) must be either 0, 1+ by
                  immunohistochemistry (if 2+, in situ hybridization method used to define HER2) OR
                  have HER2: 17 centromere signal of <2.0 using a standard in situ hybridization
                  method

          -  No prior therapy for current breast cancer

          -  Meet criteria for neoadjuvant chemotherapy or primary breast surgery, as determined by
             primary oncologist and surgeon

        Inclusion Criteria for study therapy:

          -  nEGFR positive

          -  Eastern Cooperative Oncology Group (ECOG) performance 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.

          -  Contraindication to repeat breast biopsy (neoadjuvant chemotherapy group)