Celecoxib, Fluorouracil, and Radiation Therapy in Treating Patients With Stage II or Stage III Rectal Cancer That Can Be Removed By Surgery

Vanderbilt University Medical Center

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer

Treatments

Procedure: tumor biopsy

Radiation: radiation therapy

Other: laboratory biomarker analysis

Drug: celecoxib

Procedure: conventional surgery

Drug: fluorouracil

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00336960

P30CA068485 (U.S. NIH Grant/Contract)

P50CA095103 (U.S. NIH Grant/Contract)

VICC-020031

VICC-GI-0173

VICC GI 0173

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary adenocarcinoma of the rectum
- Stage II or III disease
Distal border of tumor must be at or below the peritoneal reflection
- Distal border of the tumor must be within 12 cm of the anal verge by proctoscopic exam
Tumor must be clinically resectable
Transmural penetration beyond muscularis propria by transrectal ultrasound
No high-grade obstruction
No evidence of metastatic 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 or psychiatric condition that would preclude study treatment
No history of allergy to celecoxib or any other NSAIDs
No history of allergy to sulfonamides
No prior or concurrent malignancy except inactive noninvasive cervical carcinoma or skin cancer (excluding melanoma) or other cancer that has been disease free for ≥ 5 years

PRIOR CONCURRENT THERAPY:

No prior radiotherapy to the pelvis
At least 7 days since prior and no other concurrent COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs)
No concurrent warfarin except low-dose warfarin (1 mg/day)