Celecoxib, Fluorouracil, and Radiation Therapy in Treating Patients With Stage II or Stage III Rectal Cancer That Can Be Removed By Surgery
RATIONALE: Celecoxib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Celecoxib may make tumor cells more sensitive to radiation therapy. Giving celecoxib together with fluorouracil and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying how well giving celecoxib together with fluorouracil and radiation therapy works in treating patients with stage II or stage III rectal cancer that can be removed by surgery.
|Colorectal Cancer||Drug: celecoxib Drug: fluorouracil Procedure: conventional surgery Radiation: radiation therapy Procedure: tumor biopsy Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Pathologic complete response rate [ Time Frame: at time of surgery, day 5 ]
- Complete resection rate [ Time Frame: at time of surgery, day 5 ]
- Patterns of failure [ Time Frame: during study, beginning day 5 forward ]
- Survival [ Time Frame: at time of death ]
- Toxicity [ Time Frame: 5 days before surgery & 5 days after surgery ]
|Study Start Date:||July 2002|
|Study Completion Date:||March 2008|
|Primary Completion Date:||November 2004 (Final data collection date for primary outcome measure)|
|Experimental: treatment intervention||
twice daily beginning 5 days prior to radiotherapy and continuing until completion of radiotherapyDrug: fluorouracil
Patients receive concurrent fluorouracil IV continuously for 5 weeks.Procedure: conventional surgery
4-10 weeks after completion of chemoradiotherapyRadiation: radiation therapy
Patients undergo radiotherapy 5 days a week for 5 weeksProcedure: tumor biopsy
at baseline and then at the time of surgical resectionOther: laboratory biomarker analysis
blood and urine collected 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. specimens are evaluated for COX-2 expression, eicosanoid production, and gene and protein expression using immunohistochemistry, microarray, and mass spectrometry.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00336960
|United States, Tennessee|
|Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus|
|Nashville, Tennessee, United States, 37212|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-5671|
|Principal Investigator:||A. Bapsi Chakravarthy, MD||Vanderbilt-Ingram Cancer Center|