Phase II Study of Dasatinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death in the United States. Twenty to
seventy-five percent of patients initially treated with surgery or radiotherapy recur and
become candidates for systemic therapy. Src expression has been identified in a majority of
NSCLC cell lines and may be important in hypoxic growth and angiogenesis of NSCLC.
This phase II trial will investigate the activity of the oral Src inhibitor dasatinib in
advanced stage NSCLC. We hypothesize that the inhibition of Src pathway with dasatinib will
show anti-tumor activity in advanced NSCLC, with a tolerable safety profile.
Fresh frozen tissue is needed for the genomics analysis, thus a biopsy will be required to
participate in this trial. The genomic analysis will determine if the tumor is Src-active or
Src-inactive and responses to dasatinib compared. In stage I, 40 patients will be treated
without prior knowledge of their tumoral Src-activity. If all stage I responses are observed
in the Src-active patients, the second stage will only accrue that cohort. If all responses
are observed in the Src-inactive cohort, the activity of dasatinib and genomic determination
of dasatinib response will be re-evaluated. Otherwise, if during Stage I, responses are
observed in both cohorts, they will be accrued separately and evaluated in a two-stage
Dasatinib will be give orally twice daily and continue until progression of disease,
intolerable toxicity or patient withdrawal. Imaging studies will be done pre-treatment then
every 6 weeks to assess radiologic response to therapy.
Patients will be followed for 30 days after the last dose of dasatinib to assess toxicity.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine ability of Src pathway signature to predict tumor response associated with dasatinib treatment in previously treated patients with advanced NSCLC.
Michael Kelley, MD
United States: Institutional Review Board
|Duke University Medical Center||Durham, North Carolina 27710|
|Durham VA Medical Center||Durham, North Carolina 27705|
|Duke Raleigh||Raleigh, North Carolina 27609|