A Pilot Study of the Biologic Efficacy and Safety of the Addition of Celecoxib to a Program of Induction Chemotherapy and Neo-Adjuvant Chemo-Radiotherapy for the Treatment of Esophageal Cancer
- To measure the rates of cellular apoptosis and proliferation at baseline and during
chemoradiotherapy with and without celecoxib using biopsy samples from patients with
stage II, III, or IV esophageal cancer.
- To determine if an acceptable rate of pathologic complete remission can be achieved in
a subset of patients with potentially resectable esophageal cancer.
- To assess the safety of the addition of daily celecoxib to chemoradiotherapy.
- To estimate the median overall survival in a subset of patients with resectable
- To quantitate expression of cyclooxygenase (COX)-2 and formation of prostaglandin E2
(PGE2) in patients with esophageal cancer.
- To assess the ability of celecoxib to decrease formation of PGE2 in tumor tissue by
measuring pre- and post-treatment tumor concentrations of PGE2.
- To quantitate downstream effects of inhibition of COX-2 function in the setting of
treatment with chemotherapy.
- To measure the radiographic response rate in patients with unresectable esophageal
OUTLINE: This is a multicenter study. Patients are sequentially enrolled into 1 of 2
- Group 1: Patients receive cisplatin IV over 1 hour and irinotecan hydrochloride IV over
90 minutes on days 1, 8, 22, 29, 43, 50, 64, and 71. Patients also undergo radiotherapy
once daily 5 days a week for 5 weeks beginning on day 43.
- Group 2: Patients receive chemoradiotherapy as in group 1. Patients also receive oral
celecoxib twice daily beginning 3 days before the initiation of chemotherapy and
continuing until the completion of chemoradiotherapy.
In both groups, patients with potentially resectable disease undergo surgery no more than 12
weeks after completion of chemoradiotherapy.
Endoscopic tumor biopsy specimens are collected at baseline and on day 3 of radiotherapy.
Samples are analyzed for cyclooxygenase (COX)-2 gene and protein expression; PGE2 secretion;
apoptotic activity; caspase-3 activation; cytochrome c translocation; VEGF mRNA
quantitation; and cellular proliferation. Laboratory techniques used include RT-PCR, IHC,
enzyme immunoassay, TUNEL assay, colorimetric assay, and northern blotting.
After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 34 patients (8-10 in group 1 and 24 in group 2) will be
accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Rates of cellular apoptosis and proliferation
Measure the rates of cellular apoptotis and proliferation in esophageal cancers from biopsy samples pre-study and during chemoradiation with and without celecoxib therapy
Bert H. O'Neil, MD
UNC Lineberger Comprehensive Cancer Center
United States: Federal Government