Pilot COX-2 Activity in Early Stage Rectal Cancer -Short Term Administration of Celecoxib (SPORE)
- Determine cyclooxygenase-2 (COX-2) over-expression in tumor specimens from patients
with early-stage rectal cancer.
- Determine whether administration of a COX-2 inhibitor, celecoxib, results in changes in
tumor (COX-2 overexpressing) levels of eicosanoids but not in levels in the surrounding
normal tissue that is expected not to express COX-2.
- Determine whether surrogate markers of eicosanoid metabolism (i.e., serum VEGF levels,
tumor prostaglandin E_2 [PGE_2], and the major urinary metabolite of PGE_2 [PGE-M]) in
biological specimens from these patients correlate with changes noted in tumor tissue.
- Determine if there is a greater change in protein and gene expression from pretreatment
biopsy levels in patient tumor specimens (COX-2 overexpressing) vs specimens of
surrounding normal tissue (expected not to be COX-2 overexpressing).
OUTLINE: Patients receive oral celecoxib twice daily on days 1-5. Patients then undergo
planned local excision or definitive radical resection on day 6.
Tumor tissue and normal tissue (at least 5 cm away from the tumor) samples are collected
pretreatment. Post-treatment tissue samples are collected along with the surgery. Serum and
urine samples are obtained at baseline and after administration of celecoxib. Tumor and
normal tissue specimens are analyzed by assays measuring markers of cyclooxygenase-2 (COX-2)
activity (i.e., COX-2 mRNA and protein, tumor prostaglandin E_2 [PGE_2], and VEGF). Tissue
samples are also assessed by cDNA microarray and imaging mass spectrometry to determine
overall changes in gene and protein expression from pretreatment levels. Surrogate markers
of COX-2 activity in serum (i.e., VEGF) and urine (i.e., urinary metabolite of PGE_2
[PGE-M]) are also assessed and compared with changes noted in tumor tissue. COX-2 protein
levels are determined by immunohistochemistry in patients with limited pretreatment tumor
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Event rate of over-expression of cyclooxygenase-2
Pre and post 7 days administration of study drug
A. Bapsi Chakravarthy, MD
Vanderbilt-Ingram Cancer Center
United States: Federal Government
VICC GI 0174
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Veterans Administration||Nashville, Tennessee 37212|