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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00336960
• Other study ID #: VICC GI 0173
• Secondary ID: P50CA095103P30CA
• Status: Completed
• Phase: Phase 2
• First received: June 13, 2006
• Last updated: March 2, 2013
• Start date: July 2002
• Est. completion date: March 2008

Study information

• Verified date: March 2013
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2008
• Est. primary completion date: November 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• celecoxib
twice daily beginning 5 days prior to radiotherapy and continuing until completion of radiotherapy
• fluorouracil
Patients receive concurrent fluorouracil IV continuously for 5 weeks.

Procedure:
• conventional surgery
4-10 weeks after completion of chemoradiotherapy

Radiation:
• radiation therapy
Patients undergo radiotherapy 5 days a week for 5 weeks

Procedure:
• tumor biopsy
at baseline and then at the time of surgical resection

Other:
• 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.

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response rate		at time of surgery, day 5	No
Secondary	Complete resection rate		at time of surgery, day 5	No
Secondary	Patterns of failure		during study, beginning day 5 forward	No
Secondary	Survival		at time of death	No
Secondary	Toxicity		5 days before surgery & 5 days after surgery	Yes