Phase I Study of Erlotinib and Celecoxib in Former Smokers With Advanced Non-Small Cell Lung Cancer
I. To estimate the clinical toxicity and tolerability of erlotinib combined with celecoxib
in patients with advanced non-small cell lung cancer (NSCLC).
I. To estimate the tumor response rate of erlotinib combined with celecoxib in patients with
II. To estimate the dose of celecoxib that results in maximal induction of apoptosis,
maximal inhibition of prostaglandin E2 (PGE2) in bronchoalveolar (BAL) fluid, and maximal
inhibition of bronchial cell proliferation when combined with erlotinib.
III. To estimate the effect of erlotinib and the combination of erlotinib and celecoxib on
bronchial expression of COX-2.
IV. To estimate the effect of erlotinib and the combination of erlotinib (and celecoxib on
autophosphorylation of epidermal growth factor receptor (EGFR) in skin and endobronchial
V. To estimate the degree of correlation of autophosphorylation of EGFR in skin and
I. To estimate the effect of the combination of erlotinib and COX-2 inhibitor (celecoxib) on
the frequency of fractional allelic loss (FAL) in endobronchial biopsies, metaplasia and
dysplasia in endobronchial biopsies, and endobronchial proliferation.
OUTLINE: This is an open-label, dose-escalation study of celecoxib.
Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of celecoxib until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity. Once the MTD is determined, up to 6 additional patients
are treated at the MTD.
Patients are followed at 4 weeks.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical tolerable dose of celecoxib as measured by NCI CTCAE v3.0
United States: Food and Drug Administration
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