Phase II Study Evaluating The Safety And Response To Neoadjuvant Dasatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC).
This is a phase II study of dasatinib, a targeted biologic agent, known to inhibit Src. It
is difficult to assess outcome in phase II adjuvant trials because there is no measurable
disease to evaluate efficacy and there are many variables that could confound comparing
survival of subjects on trial to historical controls. Therefore, after a fresh frozen tumor
tissue sample is obtained for genomic analysis, we plan to treat subjects with neoadjuvant
dasatinib and then measure tumor response to therapy prior to surgery. Resected tumor will
also be assessed for pathologic response as well as for changes in genomic expression
Subjects will be treated with neoadjuvant dasatinib 70 mg PO twice daily for 3 weeks, with a
mandatory minimum of 3 days (72 hours) off of study drug prior to surgical resection.
Imaging studies will be done pre-treatment and pre-surgery to assess radiologic response to
therapy. The surgical specimen will be evaluated for pathologic response. A tumor tissue
sample will be obtained from the surgical specimen for genomic analysis and will be
evaluated for changes in genomic expression profiles.
Patients whose tumors have a response to neoadjuvant dasatinib therapy might benefit with
better cancer control if they receive a potentially therapeutic course of adjuvant
dasatinib. Patients that have at least a 15% decrease or better objective response, without
evidence of progression to neoadjuvant dasatinib (per tumor evaluation pre-surgery) or
pathologic response (as defined as ≥30% tumor necrosis or cell death) to neoadjuvant
dasatinib therapy will be eligible to receive dasatinib 70 mg twice daily for 90 days after
the completion of standard adjuvant therapy or after recovery from surgery if no standard
adjuvant therapy is given. Patients will be followed for approximately 30 days after the
last dose of dasatinib to assess toxicity.
Response will be evaluated in Src regulated and Src deregulated cohorts of tumors. If
responses to neoadjuvant dasatinib occur, then accrual to either or both cohorts will be
expanded. If there are no responses to neoadjuvant dasatinib in the cohort groups, then
accrual to either or both cohorts will be stopped. The results of this study may be useful
in designing future studies in early stage NSCLC using dasatinib alone or in combination
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate (radiologic and pathologic) in Stage IB and II to neoadjuvant dasatinib
First progression and survival every 3 months for 2 years, then every 6 months until 5 years, then yearly.
Neal Ready, M.D.
United States: Institutional Review Board
|Duke University Medical Center||Durham, North Carolina 27710|