Breast NeoplasmsPhase 2NCT02720185
Window of Opportunity Trial of Dasatinib in Operable Triple Negative Breast Cancers With nEGFR
A Phase 2 study testing Dasatinib, Conventional Surgery and Laboratory Biomarker Analysis in people with Breast Neoplasms and Triple Negative Breast Neoplasms, run by University of Wisconsin, Madison at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms, Triple Negative Breast Neoplasms
- What is being tested?
- Dasatinib, Conventional Surgery and Laboratory Biomarker Analysis
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 May 2017to 8 Feb 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- nEGFR positive
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- 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
Who cannot join
- 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.
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- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Illinois Hospital and Health Systems (Outpatient Care Center)
Chicago, Illinois, 60612
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53705
About this study
Official title: Window of Opportunity Study of Dasatinib in Operable Triple Negative Breast Cancers With Nuclear Epidermal Growth Factor Receptor (nEGFR)
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
- Conditions
- Breast Neoplasms, Triple Negative Breast Neoplasms
- Being tested
- Dasatinib, Conventional Surgery, Laboratory Biomarker Analysis
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called 732517, 863127-77-9, BMS-354825, Sprycel
100mg oral once daily dasatinib taken for 7-10 days up to the day prior to planned surgery or research biopsy (neoadjuvant chemotherapy group)
Conventional SurgeryProcedure or surgery
Undergo surgery
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Dasatinib 100mg | Experimental | Dasatinib 100mg for 7-10 days until day prior to surgery Receives: Drug: Dasatinib; Procedure: Conventional Surgery; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Membrane Epidermal Growth Factor Receptor (EGFR) Expression, Measured by VECTRA Imaging
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.
Measured: 7-10 days
Secondary outcomes (3)
Number of Treatment-emergent Adverse Events [Safety and Tolerability] 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.
Measured: Up to 4 weeks
Number of Participants With Pathologic Complete Response (pCR)
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.
Measured: Up to 4 weeks
Number of Participants With No Evidence of Disease (NED) at Long-term Follow up
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2016 (estimated)
- Study start3 May 2017
- Primary completion2 Jul 2020
- Study completion8 Feb 2022
Why it stopped: Study terminated early due to COVID-19 related slow enrollment and funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Kari B Wisinski, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02720185
- Sponsor's protocol ID
- UW15114
- Other IDs
- 1R01CA193004-01A1, NCI-2016-00237, 2015-1578, A534260, SMPH\MEDICINE\HEM-ONC, Protocol Version 8/29/2019
- Status last verified
- Jun 2022
- First submitted
- 21 Mar 2016
- Last updated
- 3 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Window of Opportunity Study of Dasatinib in Operable Triple Negative Breast Cancers With Nuclear Epidermal Growth Factor Receptor (nEGFR)
- ClinicalTrials.gov ID
- NCT02720185
- Acronym / sponsor ID
- UW15114
- Conditions
- Breast Neoplasms, Triple Negative Breast Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated early due to COVID-19 related slow enrollment and funding
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 3 May 2017 (actual)
- Primary completion
- 2 Jul 2020 (actual)
- Study completion
- 8 Feb 2022 (actual)
- First posted
- 25 Mar 2016 (estimated)
- Results
- Posted 25 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dasatinib 100mg | Experimental | Drug: Dasatinib, Procedure: Conventional Surgery, Other: Laboratory Biomarker AnalysisDasatinib 100mg for 7-10 days until day prior to surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have histologically or cytologically confirmed Stage I-III triple negative breast cancer
- No prior therapy for current breast cancer
- Meet criteria for neoadjuvant chemotherapy or primary breast surgery, as determined by primary oncologist and surgeon
- nEGFR positive
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibAlso: 732517, 863127-77-9, BMS-354825, Sprycel100mg oral once daily dasatinib taken for 7-10 days up to the day prior to planned surgery or research biopsy (neoadjuvant chemotherapy group) | Drug | Dasatinib 100mg |
| Conventional SurgeryUndergo surgery | Procedure or surgery | Dasatinib 100mg |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Dasatinib 100mg |
Primary outcome
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.
3 secondary outcomes
Number of Treatment-emergent Adverse Events [Safety and Tolerability] up to 4 Weeks
Time frame: Up to 4 weeks
Number of Participants With Pathologic Complete Response (pCR)
Time frame: Up to 4 weeks
Number of Participants With No Evidence of Disease (NED) at Long-term Follow up
Time frame: up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UW Carbone Cancer Center Home PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kari B Wisinski, MD principal investigator
University of Wisconsin, Madison
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dasatinib, Conventional Surgery and Laboratory Biomarker Analysis in people with Breast Neoplasms and Triple Negative Breast Neoplasms, run by University of Wisconsin, Madison at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Membrane Epidermal Growth Factor Receptor (EGFR) Expression, Measured by VECTRA Imaging (time frame: 7-10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2022.