Phase II Dasatinib Study in Advanced Breast Cancer

Duke University

Status and phase

Completed

Phase 2

Conditions

Advanced Breast Cancer

Treatments

Drug: Dasatinib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00546104

Pro00007578

BMS CA180089

Details and patient eligibility

About

The purpose of this study is to find out if dasatinib will safely reduce the size or spread of your tumor.

Full 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.

Enrollment

31 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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