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

Sponsor:	Vanderbilt-Ingram Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:	NCT00336960

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: celecoxib Drug: fluorouracil Procedure: conventional surgery Radiation: radiation therapy Procedure: tumor biopsy Other: laboratory biomarker analysis	Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Celecoxib

U.S. FDA Resources

Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:

Pathologic complete response rate [ Time Frame: at time of surgery, day 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete resection rate [ Time Frame: at time of surgery, day 5 ] [ Designated as safety issue: No ]
Patterns of failure [ Time Frame: during study, beginning day 5 forward ] [ Designated as safety issue: No ]
Survival [ Time Frame: at time of death ] [ Designated as safety issue: No ]
Toxicity [ Time Frame: 5 days before surgery & 5 days after surgery ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	28
Study Start Date:	July 2002
Study Completion Date:	June 2008
Primary Completion Date:	January 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: treatment intervention	Drug: celecoxib twice daily beginning 5 days prior to radiotherapy and continuing until completion of radiotherapy Drug: 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.

Arms

Assigned Interventions

Experimental: treatment intervention

Drug: celecoxib

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

Drug: 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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336960

Locations

United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-5671
Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus
Nashville, Tennessee, United States, 37212

Sponsors and Collaborators

Vanderbilt-Ingram Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

A. Bapsi Chakravarthy, MD

Vanderbilt-Ingram Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Bapsi Chak, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:	NCT00336960 History of Changes
Other Study ID Numbers:	VICC GI 0173, P50CA095103, P30CA068485, VICC-GI-0173, VICC-020031
Study First Received:	June 13, 2006
Last Updated:	May 19, 2011
Health Authority:	United States: Federal Government

Keywords provided by Vanderbilt-Ingram Cancer Center:

stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:

Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Celecoxib
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on February 09, 2012