Phase II Dasatinib Study in Advanced Breast Cancer
The purpose of this study is to find out if dasatinib will safely reduce the size or spread of your tumor.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer|
- The primary outcome is to estimate the proportion of patients who are progression-free at 16 weeks. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Assess response per RECIST criteria; characterize and compare SRC dysregulation at baseline, 4 weeks, and at progression; correlate results with response; explore association between each patient's SRC signature and their time to progression. [ Time Frame: Every 8 weeks. ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
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.
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.
|United States, Florida|
|Palm Beach Cancer Center Institute|
|West Palm Beach, Florida, United States, 33401|
|United States, North Carolina|
|Presbyterian Health Care|
|Charlotte, North Carolina, United States, 28204|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Kimberly Blackwell, MD||Duke University|