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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
A Bapsi Chakravarthy, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00336960
First received: June 13, 2006
Last updated: March 2, 2013
Last verified: March 2013
  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 2

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:


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 ]

Enrollment: 24
Study Start Date: July 2002
Study Completion Date: March 2008
Primary Completion Date: November 2004 (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.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: A. Bapsi Chakravarthy, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: A Bapsi Chakravarthy, MD, Professor of Medicine, Medical Oncologist, 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: March 2, 2013
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:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Celecoxib
Fluorouracil
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014