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”

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.

Study Type: Interventional

Study Design: Treatment

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 40 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: celecoxib
• Drug: fluorouracil
• Procedure: conventional surgery
• Procedure: gene expression analysis
• Procedure: immunohistochemistry staining method
• Procedure: laboratory biomarker analysis
• Procedure: mass spectrometry
• Procedure: neoadjuvant therapy
• Procedure: protein expression analysis
• Procedure: radiation therapy

Primary Measures

• Pathologic complete response rate
  • Safety Issue?: No
• Toxicity
  • Safety Issue?: Yes

Secondary Measures

• Complete resection rate
  • Safety Issue?: No
• Patterns of failure
  • Safety Issue?: No
• Survival
  • Safety Issue?: No

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Vanderbilt-Ingram Cancer Center

Overall Clinical Trial Officials and Contacts

A. Bapsi Chakravarthy, MD Principal Investigator Vanderbilt-Ingram Cancer Center  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00336960

Study ID Number: CDR0000481504

ClinicalTrials.gov Identifier: NCT00336960

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database