Clinical Trial: Evaluation of Surgically Resected Colorectal Adenomas and Carcinomas After 7 Days Pretreatment With Celecoxib
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Randomized, Placebo-Controlled, Phase 2B Evaluation of Cyclooxygenase-2 Activity in Surgically Resected Primary Colorectal Adenomas and Carcinomas After 7 Days Pretreatmen
Brief Summary: The purpose of this study is to assess how effective celecoxib is in limiting production of a hormone, prostaglandin, in the subject's body. It is felt that this hormone is involved in the evolution of pre-cancerous growths in the colon to cancerous stage or in the progression of an existing cancer. To answer this question, some subjects are given the new investigational drug, and other subjects a placebo. A placebo is a capsule that contains inactive ingredients. Only by comparing the response of two subject groups, one receiving placebo (inactive), and one receiving celecoxib (active), will we be able to know whether or not celecoxib actually works. The outcome we are assessing is the hormone activity before and after celecoxib is given.
Detailed Summary: We propose to test the hypothesis that celecoxib, a specific inhibitor of cyclooxygenase -2 (COX-2), will effectively inhibit the enzymatic activity in all tissues sampled after oral administration of celecoxib for 7 days preoperatively. One hundred twenty patients (120) undergoing standard surgical resection for the treatment of primary colorectal adenomas or carcinomas would be randomized to celecoxib or placebo given for 7 days prior to operation. Peripheral blood will be drawn prior to drug or placebo administration, and then morning of operation. At the time of definitive resection of the specimen, normal intestinal mucosa and primary tumor would be harvested and immediately snap frozen at -80 degrees. Levels of COX-2 activity (prostaglandin production) as well as expression of COX-2 and other markers (matrix metalloproteinases(MMPs), tissue inhibitors of MMPs (TIMPs), cell adhesion and cell cycle control molecules will be evaluated in normal mucosa and primary tumor compared between celecoxib and placebo treated patients.
Sponsor: University of Alabama at Birmingham
Current Primary Outcome:
- Number of Subjects Witha Change (IMPROVEMENT) in Colo-rectal Adenocarcinoma as Measured by Cyclooxygenase-2 Activity After 7 Days of Celecoxib [ Time Frame: baseline to 36 months ]The Colo-Rectal adenocarcinoma will be measured by cyclooxygenase-2(COX-2) activity at 36 months post baseline.COX-2 activity (prostaglandin production).Cox-2 activity is measured by assessing tumors and normal tissue using "Electron microscope and Tandem mass Spectrometry" methodology though the UAB shared Mass Spectrometry facility. The methodology used was High Performance Liquid Chromatography(HPLC). additional studies include expression of genes thought to be important in colorectal carcinogenesis: COX-1 and 2, MMP, 2 7, and 9, tissue inhibitor of metalloproteinases(TIMPs) 1 ans 2 and beta-catenin.
- Subjects With Positive Response 72 Hours After Administration of Study Treatment as Measured by Immunoblot [ Time Frame: baseline to 72 hours ]At 72 hours after start of treatment, the number of subjects with immunoblot demonstrated a 1.5 to 2 fold increase in 15-LOX-1 protein expression in human colorectal adenocarcinoma cell line with epithelial morphology(HT-29) and dihydrolipoamide dehydrogenase(DLD)-1 cells.
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: University of Alabama at Birmingham
Dates:
Date Received: December 20, 2007
Date Started: December 2001
Date Completion:
Last Updated: July 15, 2014
Last Verified: July 2014
