A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 3
- 主要终点
- Estimation of the Proportion of Progression-free Patients at 16 Wks.
研究概览
简要总结
The purpose of this study is to find out if dasatinib will safely reduce the size or spread of your tumor.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
研究组 & 干预措施
Dasatinib
50- 100 mg PO BID
干预措施: Dasatinib (Drug)
结局指标
主要结局
Estimation of the Proportion of Progression-free Patients at 16 Wks.
时间窗: 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.
次要结局
- To Measure Response to Protocol Therapy Per RECIST Criteria(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)(4 weeks)
- Correlate SRC Dysregulation Results With Response to Dasatinib Therapy(16 weeks)
- To Explore the Association Between Each Patient's SRC Signature and Their Time to Progression.(Baseline Src measure to first progression)
- To Explore the Association Between Dasatinib and Osteoclastic Bone Resorption(not assessed)