Trial Information

Phase II Pilot Study of Pre-Operative Celecoxib (Celebrex) in Combination With Prolonged Venous Infusion 5FU and Radiation Therapy for Patients With Stage II/III Resectable Rectal Cancer

OBJECTIVES:

- Determine cyclo-oxygenase-2 (COX-2) overexpression in patients with resectable stage II
or III rectal cancer treated with neoadjuvant celecoxib, fluorouracil, and
radiotherapy.

- Determine whether administration of celecoxib, a COX-2 inhibitor, results in changes in
tumor (COX-2 overexpressing) levels of eicosanoids but not in the surrounding normal
tissue.

- Determine if there is a greater change in protein and gene expression in post-treatment
biopsies when compared to pretreatment biopsies that are greater for tumor (COX-2
overexpression) than in surrounding normal tissue.

- Determine whether patients who express the greatest degree of change in gene and
protein expression are those most likely to respond to therapy.

- Assess the toxicities of concurrent treatment with celecoxib, fluorouracil, and
radiotherapy.

OUTLINE: This is a pilot study.

Patients receive oral celecoxib twice daily beginning 5 days prior to radiotherapy and
continuing until completion of radiotherapy. Patients undergo radiotherapy 5 days a week for
5 weeks. Patients also receive concurrent fluorouracil IV continuously for 5 weeks. Patients
undergo radical resection 4-10 weeks after completion of chemoradiotherapy.

Patients undergo tumor biopsy at baseline and then at the time of surgical resection.
Patients also undergo blood and urine collection at baseline, 5 days after initiation of
celecoxib, 7 days after initiation of celecoxib in combination with fluorouracil and
radiotherapy, and at the time of surgical resection. The specimens are evaluated for COX-2
expression, eicosanoid production, and gene and protein expression using
immunohistochemistry, microarray, and mass spectrometry.

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 28 patients will be accrued for this study.