Celecoxib, Fluorouracil, and Radiation Therapy in Treating Patients With Stage II or Stage III Rectal Cancer That Can Be Removed By Surgery
- Conditions
- Colorectal Cancer
- Interventions
- Procedure: conventional surgeryRadiation: radiation therapyProcedure: tumor biopsyOther: laboratory biomarker analysis
- Registration Number
- NCT00336960
- Lead Sponsor
- Vanderbilt-Ingram Cancer Center
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description treatment intervention tumor biopsy - treatment intervention celecoxib - treatment intervention fluorouracil - treatment intervention conventional surgery - treatment intervention radiation therapy - treatment intervention laboratory biomarker analysis -
- Primary Outcome Measures
Name Time Method Pathologic complete response rate at time of surgery, day 5
- Secondary Outcome Measures
Name Time Method Complete resection rate at time of surgery, day 5 Patterns of failure during study, beginning day 5 forward Survival at time of death Toxicity 5 days before surgery & 5 days after surgery
Trial Locations
- Locations (2)
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
🇺🇸Nashville, Tennessee, United States