Celecoxib in Treating Patients With Early-Stage Rectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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.

Official Title
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Pilot COX-2 Activity in Early Stage Rectal Cancer -Short Term Administration of Celecoxib (SPORE)

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: celecoxib
* Genetic: gene expression analysis
* Genetic: protein expression analysis
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Other: mass spectrometry
* Procedure: biopsy
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of primary adenocarcinoma of the rectum (to be histologically confirmed upon study entry) Tumor must be at or below the peritoneal reflection The distal border of the tumor is within 12 cm of the anal verge on proctoscopic examination Clinically resectable disease PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% WBC ≥ 4,000/mm³ Platelet count ≥ 150,000/mm³ Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other serious medical illness (other than rectal cancer) that would preclude study therapy No psychiatric condition that would preclude informed consent No history of allergy to celecoxib or any other NSAIDs, including acetylsalicylic acid (i.e., aspirin), ibuprofen, or indomethacin No history of allergy to sulfonamides Exclusion criteria: Not noted PRIOR CONCURRENT THERAPY: At least 7 days since prior and no concurrent NSAIDs or other cyclooxygenase-2 inhibitors No concurrent warfarin, except low-dose warfarin (i.e., 1 mg/day) administered for prophylaxis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Intervention/Celecoxib<br>Celecoxib | Drug: celecoxib<br>* Will be administered orally 400 mg po BID starting 5 days prior to planned surgical resection.<br>* Other names: Celebrex;Genetic: gene expression analysis<br>* not noted<br>Genetic: protein expression analysis<br>* Not noted<br>Other: immunohistochemistry staining method<br>* not noted<br>Other: laboratory biomarker analysis<br>* not noted<br>Other: mass spectrometry<br> <br> Procedure: biopsy<br>* At the time of preoperative evaluation by surgeon as well as one week after administration of Celecoxib.<br>Procedure: neoadjuvant therapy<br>* not noted<br>Procedure: therapeutic conventional surgery<br>* not noted<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event rate of over-expression of cyclooxygenase-2 |  | Pre and post 7 days administration of study drug | 
| Percent change of eicosanoid level |  | Pre and post celecoxib treatment ratio of eicosanoid production | 
| Percent change of VEGF and prostaglandin-M levels |  | Pre and post celecoxib treatment VEGF and PGE-M levels | 
| Change of gene and protein expression pattern from pre- to post-treatment levels |  | Pre and post celecoxib treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the rectum, recurrent rectal cancer, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer