Clinical trial NCT00608595: Celecoxib in Treating Patients With Early-Stage Rectal Cancer
Official title: Pilot COX-2 Activity in Early Stage Rectal Cancer -Short Term Administration of Celecoxib (SPORE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
recurrent rectal cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-02-06
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Event rate of over-expression of cyclooxygenase-2
timeFrame: Pre and post 7 days administration of study drug
measure: Percent change of eicosanoid level
timeFrame: Pre and post celecoxib treatment ratio of eicosanoid production
measure: Percent change of VEGF and prostaglandin-M levels
timeFrame: Pre and post celecoxib treatment VEGF and PGE-M levels
measure: Change of gene and protein expression pattern from pre- to post-treatment levels
timeFrame: Pre and post celecoxib treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Veterans Administration
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: A. Bapsi Chakravarthy, MD
role: PRINCIPAL_INVESTIGATOR
References: