Advanced Breast CancerPhase 2NCT00546104
Phase II Dasatinib Study in Advanced Breast Cancer
A Phase 2 study testing Dasatinib in people with Advanced Breast Cancer, run by Duke University at 3 sites in United States.
Trial summary
The purpose of this study is to find out if dasatinib will safely reduce the size or spread of your tumor. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- Dasatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2007to May 2011
- 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
- Measurable Stage IV or inoperable Stage III advanced breast cancer.
- There is no limit on the number of prior therapies.
- At least 3 weeks since prior chemotherapy, biological or hormonal therapy.
- At least 2 weeks since surgical biopsy.
- At least 3 weeks since major (open thoracic/abdominal/cardiac) surgery.
- No central nervous system (CNS) metastases except solitary brain metastasis
Show all 12Show fewer
- No cardiac dysfunction
- left ventricular ejection fraction (LVEF) ≥ 50% as determined by multiple gated acquisition scan (MUGA)/echocardiogram
- Adequate blood counts
- Normal liver and kidney function
- Negative serum pregnancy test.
- Able to provide informed consent
Who cannot join
- Pregnant or breast feeding.
- Prior treatment with dasatinib.
- Bone as the only site of disease.
- Significant gastrointestinal bleeding
- Septicemia, infection, acute hepatitis, hypokalemia, or hypomagnesemia
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Presbyterian Health Care
Charlotte, North Carolina, 28204
Duke University Medical Center
Durham, North Carolina, 27710
Palm Beach Cancer Center Institute
West Palm Beach, Florida, 33401
About this study
Official title: A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer
The purpose of this study is to find out if dasatinib will safely reduce the size or spread of your tumor.
Read the detailed description
The introduction of biologics with specific molecular targets has initiated a trend toward improved survival in women with metastatic breast cancer.
The tyrosine kinase SRC (pp60src) is a member of a family of proteins that contribute to cellular signal transduction activities such as cell growth, differentiation, survival, adhesion and migration. Abnormal signaling has been linked to cancer metastases; thus, identification of molecular regulators or inhibitors of SRC present therapeutic opportunity for cancer patients. Src kinases consist of eight non-receptor tyrosine kinases (Src, Fyn, Yes, Lck, Lyn, Hck, Fgr and Blk) that interact with the intracellular domains of growth factor/cytokine receptors, (G-protein-coupled receptor)GPCRs and integrins.
Inhibition of SRC has also been associated with reversal of chemoresistance and restored sensitivity to drug-resistant ovarian cancer cells, suggesting potential as second- line treatment for previously treated populations. Dasatinib is a potent, broad spectrum inhibitor of 5 critical oncogenic tyrosine kinases, including SRC.
Patients will receive dasatinib, a Src inhibitor, at an initial dose of 50 mg PO BID, with real-time PharmacoDynamic dose adjustment following 4 weeks of therapy based on inhibition of phosphorylation of SRC, focal adhesion kinase (FAK) and paxillin, until progression. The primary objective is to assess tolerability and estimate the proportion of patients who are progression-free at 16 weeks from the date of study enrollment.
A minimum of 2 (maximum of 3) tumor biopsies will be analyzed and compared for SRC signature: one at baseline (study enrollment, all patients); the second after 4 weeks of dasatinib therapy (all patients); and the third at progression (only patients who progress after a documented response).
Patients will receive continuous daily administration until documented disease progression, and will be followed until death.
The results of this study may be useful in designing future studies using dasatinib alone or in combination with chemotherapy, thus having the potential to alter the current standard of care in this incurable population.
Additional correlative studies will be conducted. Tumor biopsies will be analyzed and compared for SRC, pSRC, Ki67, and related genomic signatures.
- Conditions
- Advanced Breast Cancer
- Being tested
- Dasatinib
- Keywords
- Advanced Breast Cancer, Breast cancer, Dasatinib, Inoperable Stage III Breast Cancer, Metastatic Breast Cancer, Stage IV Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called Sprycel, BMS-354825
An initial dose of 50 mg PO BID; following 4 weeks of treatment, dose adjustment will be based on inhibition of phosphorylation of FAK and paxillin per biopsy assessment, as well as toxicity assessment.
| Study group | Role | What they receive |
|---|---|---|
| Dasatinib | Experimental | 50- 100 mg PO BID Receives: Drug: Dasatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimation of the Proportion of Progression-free Patients at 16 Wks.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as appropriate.
Proportion progression-free at 16 weeks.From first day of study related treatment with Dasatinib until the date of first documented progression or date of death from any cause, whichever came first.
Measured: 16 weeks
Secondary outcomes (5)
To Measure Response to Protocol Therapy Per RECIST Criteria
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression At least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as a reference the smallest sum longest diameter recorded since treatment started, or the appearance of one or more new lesions.
RECIST 1.0 Overall response:
Complete Response (CR) Partial Response (PR) Stable Disease (SD) Progressive Disease (PD)
CR= CR+CR and No new lesions PR= CR+SD; PR+SD and no new lesions SD= SD+SD and no new lesions PD= PD+any new lesions
Measured: 16 weeks
Characterization and Comparison of SRC (A Protein Tyrosine Kinase)Dysregulation at Baseline (All Patients), After 4 Weeks of Dasatinib Treatment (All Patients), and at Progression (Only Patients Who Progress After Documented Response)
For the 20 patients with evaluable biopsies at baseline and week 4, the median relative change from baseline in tissue biomarker levels of phospho-Src (p-Src)
Measured: 4 weeks
Correlate SRC Dysregulation Results With Response to Dasatinib Therapy
Since all patients progressed there is no comparison to between responders and non-responders.
Measured: 16 weeks
To Explore the Association Between Each Patient's SRC Signature and Their Time to Progression.
Spearman's correlation between the change in SRC signature from baseline to 4 weeks and time to progression
Measured: Baseline Src measure to first progression
To Explore the Association Between Dasatinib and Osteoclastic Bone Resorption
Not assessed secondary to limited number of subjects.
Measured: not assessed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionMay 2011
- Study completionMay 2011
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 Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Kimberly Blackwell, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00546104
- Sponsor's protocol ID
- Pro00007578
- Other IDs
- BMS CA180089
- Status last verified
- Jul 2013
- First submitted
- 16 Oct 2007
- Last updated
- 17 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00546104
- Acronym / sponsor ID
- Pro00007578
- Conditions
- Advanced Breast Cancer
- Keywords
- Advanced Breast Cancer, Breast cancer, Dasatinib, Inoperable Stage III Breast Cancer, Metastatic Breast Cancer, Stage IV Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Oct 2007
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 18 Oct 2007 (estimated)
- Results
- Posted 17 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out if dasatinib will safely reduce the size or spread of your tumor.
Detailed description
The introduction of biologics with specific molecular targets has initiated a trend toward improved survival in women with metastatic breast cancer.
The tyrosine kinase SRC (pp60src) is a member of a family of proteins that contribute to cellular signal transduction activities such as cell growth, differentiation, survival, adhesion and migration. Abnormal signaling has been linked to cancer metastases; thus, identification of molecular regulators or inhibitors of SRC present therapeutic opportunity for cancer patients. Src kinases consist of eight non-receptor tyrosine kinases (Src, Fyn, Yes, Lck, Lyn, Hck, Fgr and Blk) that interact with the intracellular domains of growth factor/cytokine receptors, (G-protein-coupled receptor)GPCRs and integrins.
Inhibition of SRC has also been associated with reversal of chemoresistance and restored sensitivity to drug-resistant ovarian cancer cells, suggesting potential as second- line treatment for previously treated populations. Dasatinib is a potent, broad spectrum inhibitor of 5 critical oncogenic tyrosine kinases, including SRC.
Patients will receive dasatinib, a Src inhibitor, at an initial dose of 50 mg PO BID, with real-time PharmacoDynamic dose adjustment following 4 weeks of therapy based on inhibition of phosphorylation of SRC, focal adhesion kinase (FAK) and paxillin, until progression. The primary objective is to assess tolerability and estimate the proportion of patients who are progression-free at 16 weeks from the date of study enrollment.
A minimum of 2 (maximum of 3) tumor biopsies will be analyzed and compared for SRC signature: one at baseline (study enrollment, all patients); the second after 4 weeks of dasatinib therapy (all patients); and the third at progression (only patients who progress after a documented response).
Patients will receive continuous daily administration until documented disease progression, and will be followed until death.
The results of this study may be useful in designing future studies using dasatinib alone or in combination with chemotherapy, thus having the potential to alter the current standard of care in this incurable population.
Additional correlative studies will be conducted. Tumor biopsies will be analyzed and compared for SRC, pSRC, Ki67, and related genomic signatures.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dasatinib | Experimental | Drug: Dasatinib50- 100 mg PO BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Measurable Stage IV or inoperable Stage III advanced breast cancer.
- There is no limit on the number of prior therapies.
- At least 3 weeks since prior chemotherapy, biological or hormonal therapy.
- At least 2 weeks since surgical biopsy.
- At least 3 weeks since major (open thoracic/abdominal/cardiac) surgery.
Key exclusion criteria (5 listed)
- Pregnant or breast feeding.
- Prior treatment with dasatinib.
- Bone as the only site of disease.
- Significant gastrointestinal bleeding
- Septicemia, infection, acute hepatitis, hypokalemia, or hypomagnesemia
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: Sprycel, BMS-354825An initial dose of 50 mg PO BID; following 4 weeks of treatment, dose adjustment will be based on inhibition of phosphorylation of FAK and paxillin per biopsy assessment, as well as toxicity assessment. | Drug | Dasatinib |
Primary outcome
Estimation of the Proportion of Progression-free Patients at 16 Wks.
Time frame: 16 weeks
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as appropriate. Proportion progression-free at 16 weeks.From first day of study related treatment with Dasatinib until the date of first documented progression or date of death from any cause, whichever came first.
5 secondary outcomes
To Measure Response to Protocol Therapy Per RECIST Criteria
Time frame: 16 weeks
Characterization and Comparison of SRC (A Protein Tyrosine Kinase)Dysregulation at Baseline (All Patients), After 4 Weeks of Dasatinib Treatment (All Patients), and at Progression (Only Patients Who Progress After Documented Response)
Time frame: 4 weeks
Correlate SRC Dysregulation Results With Response to Dasatinib Therapy
Time frame: 16 weeks
To Explore the Association Between Each Patient's SRC Signature and Their Time to Progression.
Time frame: Baseline Src measure to first progression
To Explore the Association Between Dasatinib and Osteoclastic Bone Resorption
Time frame: not assessed
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kimberly Blackwell, MD principal investigator
Duke University
3 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 in people with Advanced Breast Cancer, run by Duke University at 3 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 12 inclusion and 5 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: finished, as of the sponsor's last update on 17 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 17 Jul 2013). 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?
Estimation of the Proportion of Progression-free Patients at 16 Wks. (time frame: 16 weeks). 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 17 Jul 2013.