Phase II Dasatinib Study in Advanced Breast Cancer

NCT ID: NCT00546104

Last Updated: 2013-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2011-05-31

Brief Summary

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.

Conditions

Advanced Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dasatinib

50- 100 mg PO BID

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

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.

Interventions

Dasatinib

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.

Intervention Type: DRUG

Other Intervention Names

Sprycel; BMS-354825

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kimberly Blackwell, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Palm Beach Cancer Center Institute

West Palm Beach, Florida, United States

Presbyterian Health Care

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

BMS CA180089

Identifier Type: -

Identifier Source: secondary_id

Pro00007578

Identifier Type: -

Identifier Source: org_study_id