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

NCT ID: NCT00336960

Last Updated: 2013-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31
• Study Completion Date: 2008-03-31

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment intervention

Group Type: EXPERIMENTAL

celecoxib

Intervention Type: DRUG

twice daily beginning 5 days prior to radiotherapy and continuing until completion of radiotherapy

fluorouracil

Intervention Type: DRUG

Patients receive concurrent fluorouracil IV continuously for 5 weeks.

conventional surgery

Intervention Type: PROCEDURE

4-10 weeks after completion of chemoradiotherapy

radiation therapy

Intervention Type: RADIATION

Patients undergo radiotherapy 5 days a week for 5 weeks

tumor biopsy

Intervention Type: PROCEDURE

at baseline and then at the time of surgical resection

laboratory biomarker analysis

Intervention Type: OTHER

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.

Interventions

celecoxib

twice daily beginning 5 days prior to radiotherapy and continuing until completion of radiotherapy

Intervention Type: DRUG

fluorouracil

Patients receive concurrent fluorouracil IV continuously for 5 weeks.

Intervention Type: DRUG

conventional surgery

4-10 weeks after completion of chemoradiotherapy

Intervention Type: PROCEDURE

radiation therapy

Patients undergo radiotherapy 5 days a week for 5 weeks

Intervention Type: RADIATION

tumor biopsy

at baseline and then at the time of surgical resection

Intervention Type: PROCEDURE

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

A Bapsi Chakravarthy, MD

Professor of Medicine, Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

A. Bapsi Chakravarthy, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

P50CA095103

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VICC-GI-0173

Identifier Type: -

Identifier Source: secondary_id

VICC-020031

Identifier Type: -

Identifier Source: secondary_id

VICC GI 0173

Identifier Type: -

Identifier Source: org_study_id