Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02720185
Recruitment Status : Recruiting
First Posted : March 25, 2016
Last Update Posted : December 11, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Breast Neoplasms Triple Negative Breast Neoplasms Drug: Dasatinib Procedure: Conventional Surgery Other: Laboratory Biomarker Analysis Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Window of Opportunity Study of Dasatinib in Operable Triple Negative Breast Cancers With Nuclear Epidermal Growth Factor Receptor
Actual Study Start Date : May 3, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Dasatinib

Arm Intervention/treatment
Experimental: Dasatinib 100mg
Dasatinib 100mg for 7-10 days until day prior to surgery
Drug: Dasatinib
100mg oral once daily dasatinib taken for 7-10 days up to the day prior to planned surgery or research biopsy (neoadjuvant chemotherapy group)
Other Names:
  • 732517
  • 863127-77-9
  • BMS-354825
  • Sprycel

Procedure: Conventional Surgery
Undergo surgery

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Increase in plasma membrane EGFR expression, measured by VECTRA [ Time Frame: 7-10 days ]
    An increase of at least 25% from baseline to post-dasatinib treatment will be considered significant.


Secondary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [safety and tolerability] [ Time Frame: Up to 4 weeks ]
    Safety and tolerability of dasatinib in participants with operable TNBC will be based on NCIC Adverse Events Version 4.0 and will be assessed by frequency tables.

  2. Pathologic Complete Response (pCR) [ Time Frame: Up to 4 weeks ]
    Examine pCR rates to standard neoadjuvant chemotherapy in nEGFR+ TNBC. pCR will be defined as ypT0 ypNO (absence of cancer in breast tissue and lymph nodes) an assessed by the investigator. The point estimate of pCR and it's exact 95% confidence intervals will be calculated.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for nEGFR testing:

  • Patients must have histologically or cytologically confirmed Stage I-III triple negative breast cancer

    • ER and PR must be <1% by standard assay methods
    • 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
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02720185


Contacts
Layout table for location contacts
Contact: Cancer Connect 800-622-8922 cancerconnect@uwcarbone.wisc.edu

Locations
Layout table for location information
United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53705
Contact: Cancer Connect    800-622-8922    cancerconnect@uwcarbone.wisc.edu   
Principal Investigator: Kari B Wisinski, MD         
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Kari B Wisinski, MD University of Wisconsin, Madison

Additional Information:
Layout table for additonal information
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT02720185     History of Changes
Other Study ID Numbers: UW15114
1R01CA193004-01A1 ( U.S. NIH Grant/Contract )
NCI-2016-00237 ( Registry Identifier: CTRP )
2015-1578 ( Other Identifier: IRB )
P30CA014520 ( U.S. NIH Grant/Contract )
First Posted: March 25, 2016    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action