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A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer

Phase 2
18 Years
Not Enrolling
Advanced Breast Cancer

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Trial Information

A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer

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.

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 CNS metastases except solitary brain metastasis

- No cardiac dysfunction

- LVEF ≥ 50% as determined by MUGA/echocardiogram

- Adequate blood counts

- Normal liver and kidney function

- Negative serum pregnancy test.

- Able to provide informed consent

Exclusion Criteria:

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary outcome is to estimate the proportion of patients who are progression-free at 16 weeks.

Outcome Time Frame:

16 weeks

Safety Issue:


Principal Investigator

Kimberly Blackwell, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Institutional Review Board

Study ID:




Start Date:

October 2007

Completion Date:

May 2011

Related Keywords:

  • Advanced Breast Cancer
  • Advanced Breast Cancer
  • Breast cancer
  • Dasatinib
  • Inoperable Stage III Breast Cancer
  • Metastatic Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms



Duke University Medical Center Durham, North Carolina  27710
Palm Beach Cancer Center Institute West Palm Beach, Florida  33401-3406
Presbyterian Health Care Charlotte, North Carolina  28204