Celecoxib in Treating Patients With Early-Stage Rectal Cancer

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00608595
• Other study ID #: VICC GI 0174
• Secondary ID: VU-VICC-GI-0174
• Status: Terminated
• Phase: N/A
• First received: January 30, 2008
• Last updated: March 2, 2013
• Start date: July 2002
• Est. completion date: April 2008

Study information

• Verified date: March 2013
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: April 2008
• Est. primary completion date: May 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• celecoxib
Will be administered orally 400 mg po BID starting 5 days prior to planned surgical resection.

Genetic:
• gene expression analysis
not noted
• protein expression analysis
Not noted

Other:
• immunohistochemistry staining method
not noted
• laboratory biomarker analysis
not noted
• mass spectrometry
Not specified

Procedure:
• biopsy
At the time of preoperative evaluation by surgeon as well as one week after administration of Celecoxib.
• neoadjuvant therapy
not noted
• therapeutic conventional surgery
not noted

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Veterans Administration	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event rate of over-expression of cyclooxygenase-2		Pre and post 7 days administration of study drug	No
Primary	Percent change of eicosanoid level		Pre and post celecoxib treatment ratio of eicosanoid production	No
Primary	Percent change of VEGF and prostaglandin-M levels		Pre and post celecoxib treatment VEGF and PGE-M levels	No
Primary	Change of gene and protein expression pattern from pre- to post-treatment levels		Pre and post celecoxib treatment	No