Celecoxib in Treating Patients With Early-Stage Rectal Cancer
RATIONALE: Studying samples of tissue, blood, and urine from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how rectal cancer will respond to treatment with celecoxib.
PURPOSE: This clinical trial is studying how well celecoxib works in treating patients with early-stage rectal cancer.
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: mass spectrometry
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot COX-2 Activity in Early Stage Rectal Cancer -Short Term Administration of Celecoxib (SPORE)|
- Event rate of over-expression of cyclooxygenase-2 [ Time Frame: Pre and post 7 days administration of study drug ] [ Designated as safety issue: No ]
- Percent change of eicosanoid level [ Time Frame: Pre and post celecoxib treatment ratio of eicosanoid production ] [ Designated as safety issue: No ]
- Percent change of VEGF and prostaglandin-M levels [ Time Frame: Pre and post celecoxib treatment VEGF and PGE-M levels ] [ Designated as safety issue: No ]
- Change of gene and protein expression pattern from pre- to post-treatment levels [ Time Frame: Pre and post celecoxib treatment ] [ Designated as safety issue: No ]
|Study Start Date:||July 2002|
|Study Completion Date:||April 2008|
|Primary Completion Date:||May 2004 (Final data collection date for primary outcome measure)|
Experimental: Therapeutic Intervention/Celecoxib
Will be administered orally 400 mg po BID starting 5 days prior to planned surgical resection.
Other Name: CelebrexGenetic: gene expression analysis
not notedGenetic: protein expression analysis
Not notedOther: immunohistochemistry staining method
not notedOther: laboratory biomarker analysis
not notedOther: mass spectrometry
Not specifiedProcedure: biopsy
At the time of preoperative evaluation by surgeon as well as one week after administration of Celecoxib.Procedure: neoadjuvant therapy
not notedProcedure: therapeutic conventional surgery
- 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 tissue specimens.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00608595
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Nashville, Tennessee, United States, 37212|
|Principal Investigator:||A. Bapsi Chakravarthy, MD||Vanderbilt-Ingram Cancer Center|