Clinical Trials /

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

NCT02720185

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 2

Trial Eligibility

Document

The Window of Opportunity of Dasatinib in Operable <span class="go-doc-concept go-doc-keyword">Triple Negative</span> Breast Cancers With nEGFR

Title

  • Brief Title: The Window of Opportunity of Dasatinib in Operable Triple Negative Breast Cancers With nEGFR
  • Official Title: A Window of Opportunity Study of Dasatinib in Operable Triple Negative Breast Cancers With Nuclear Epidermal Growth Factor Receptor
  • Clinical Trial IDs

    NCT ID: NCT02720185

    ORG ID: UW15114

    NCI ID: 1R01CA193004-01A1

    Trial Conditions

    Breast Neoplasms

    Triple Negative Breast Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    Dasatinib 732517, 863127-77-9, BMS-354825, Sprycel Dasatinib 100mg

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Dasatinib 100mg Experimental Dasatinib 100mg for 7-10 days until day prior to surgery Dasatinib

    Eligibility Criteria

    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

    Primary Outcome Measures

    Increase in plasma membrane EGFR expression, measured by VECTRA

    Secondary Outcome Measures

    Trial Keywords