A Phase 2 Study of Dasatinib in Head and Neck Squamous Cell Carcinoma
I. To determine the 12-week progression-free survival rate and the objective response rate,
as measured by RECIST criteria, in patients with recurrent or metastatic squamous cell
carcinoma of the head and neck treated with dasatinib.
I. To define metabolic response rate by PET scan at 0, 8, and 12 weeks. II. To define
overall survival distribution from initiation of dasatinib. III. To define duration of
response. IV. To determine if there is a correlation between clinical benefit from dasatinib
(defined as disease response or stabilization) and pharmacokinetics (PK), pharmacodynamics
(pSrc expression in platelets), or changes in serum levels of cytokines, growth factors, and
growth factor receptors relevant to the Src signaling pathway.
V. To examine the relationship between clinical benefit and EMS1 gene amplification and
cortactin expression levels in tumor tissue prior to therapy and the modulation of cortactin
levels by treatment (if post-treatment biopsy available).
VI. To compare the effects of dasatinib on apoptosis by TUNEL assay using pre- vs
post-treatment tumor tissue biopsy samples.
VII. To assess the tolerability of dasatinib in this patient population. VIII. To describe
the PK profile and relative bioavailability of dasatinib suspension in patients receiving
the drug through percutaneous gastrostomy tube.
IX. To descriptively assess safety, toxicity, and efficacy of dasatinib crushed and
administered by feeding tube.
OUTLINE: Patients receive dasatinib orally or by percutaneous gastrostomy tube twice daily
on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, and biomarker
correlative studies. Techniques used include LC/MS assay, ELISA, and protein multiplex
immunoassay. Paraffin-embedded tumor tissue samples are analyzed for EMS1 gene amplification
and cortactin expression levels by FISH and IHC and apoptosis by TUNEL assay.
After completion of study treatment, patients are followed for at least 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Progression-free Survival at 12-weeks
Progression-free survival (PFS) is defined as stable disease or better. Participants who have received at least one dose of dasatinib and who die or leave the study before 12 weeks will be counted as having progressive disease.
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M D Anderson Cancer Center||Houston, Texas 77030|