Celecoxib in Treating Patients With Early-Stage Rectal Cancer

This study has been terminated.
(low accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
A Bapsi Chakravarthy, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00608595
First received: January 30, 2008
Last updated: March 2, 2013
Last verified: March 2013
  Purpose

RATIONALE: Studying samples of tissue, blood, and urine from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how rectal cancer will respond to treatment with celecoxib.

PURPOSE: This clinical trial is studying how well celecoxib works in treating patients with early-stage rectal cancer.


Condition Intervention
Colorectal Cancer
Drug: celecoxib
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: mass spectrometry
Procedure: biopsy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot COX-2 Activity in Early Stage Rectal Cancer -Short Term Administration of Celecoxib (SPORE)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event rate of over-expression of cyclooxygenase-2 [ Time Frame: Pre and post 7 days administration of study drug ] [ Designated as safety issue: No ]
  • Percent change of eicosanoid level [ Time Frame: Pre and post celecoxib treatment ratio of eicosanoid production ] [ Designated as safety issue: No ]
  • Percent change of VEGF and prostaglandin-M levels [ Time Frame: Pre and post celecoxib treatment VEGF and PGE-M levels ] [ Designated as safety issue: No ]
  • Change of gene and protein expression pattern from pre- to post-treatment levels [ Time Frame: Pre and post celecoxib treatment ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: July 2002
Study Completion Date: April 2008
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therapeutic Intervention/Celecoxib
Celecoxib
Drug: celecoxib
Will be administered orally 400 mg po BID starting 5 days prior to planned surgical resection.
Other Name: Celebrex
Genetic: gene expression analysis
not noted
Other Name: gene expression analysis
Genetic: protein expression analysis
Not noted
Other Name: protein expression analysis
Other: immunohistochemistry staining method
not noted
Other Name: immunohistochemistry staining method
Other: laboratory biomarker analysis
not noted
Other Name: laboratory biomarker analysis
Other: mass spectrometry
Not specified
Other Name: mass spectrometry
Procedure: biopsy
At the time of preoperative evaluation by surgeon as well as one week after administration of Celecoxib.
Other Name: biopsy
Procedure: neoadjuvant therapy
not noted
Other Name: neoadjuvant therapy
Procedure: therapeutic conventional surgery
not noted
Other Name: therapeutic conventional surgery

Detailed Description:

OBJECTIVES:

  • Determine cyclooxygenase-2 (COX-2) over-expression in tumor specimens from patients with early-stage rectal cancer.
  • Determine whether administration of a COX-2 inhibitor, celecoxib, results in changes in tumor (COX-2 overexpressing) levels of eicosanoids but not in levels in the surrounding normal tissue that is expected not to express COX-2.
  • Determine whether surrogate markers of eicosanoid metabolism (i.e., serum VEGF levels, tumor prostaglandin E_2 [PGE_2], and the major urinary metabolite of PGE_2 [PGE-M]) in biological specimens from these patients correlate with changes noted in tumor tissue.
  • Determine if there is a greater change in protein and gene expression from pretreatment biopsy levels in patient tumor specimens (COX-2 overexpressing) vs specimens of surrounding normal tissue (expected not to be COX-2 overexpressing).

OUTLINE: Patients receive oral celecoxib twice daily on days 1-5. Patients then undergo planned local excision or definitive radical resection on day 6.

Tumor tissue and normal tissue (at least 5 cm away from the tumor) samples are collected pretreatment. Post-treatment tissue samples are collected along with the surgery. Serum and urine samples are obtained at baseline and after administration of celecoxib. Tumor and normal tissue specimens are analyzed by assays measuring markers of cyclooxygenase-2 (COX-2) activity (i.e., COX-2 mRNA and protein, tumor prostaglandin E_2 [PGE_2], and VEGF). Tissue samples are also assessed by cDNA microarray and imaging mass spectrometry to determine overall changes in gene and protein expression from pretreatment levels. Surrogate markers of COX-2 activity in serum (i.e., VEGF) and urine (i.e., urinary metabolite of PGE_2 [PGE-M]) are also assessed and compared with changes noted in tumor tissue. COX-2 protein levels are determined by immunohistochemistry in patients with limited pretreatment tumor tissue specimens.

  Eligibility

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

Inclusion Criteria:

  • Clinical diagnosis of primary adenocarcinoma of the rectum (to be histologically confirmed upon study entry)

    • Tumor must be at or below the peritoneal reflection
    • The distal border of the tumor is within 12 cm of the anal verge on proctoscopic examination
  • Clinically resectable 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 (other than rectal cancer) that would preclude study therapy
  • No psychiatric condition that would preclude informed consent
  • No history of allergy to celecoxib or any other NSAIDs, including acetylsalicylic acid (i.e., aspirin), ibuprofen, or indomethacin
  • No history of allergy to sulfonamides

Exclusion criteria:

Not noted

PRIOR CONCURRENT THERAPY:

  • At least 7 days since prior and no concurrent NSAIDs or other cyclooxygenase-2 inhibitors
  • No concurrent warfarin, except low-dose warfarin (i.e., 1 mg/day) administered for prophylaxis
  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: NCT00608595

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Veterans Administration
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: NCT00608595     History of Changes
Other Study ID Numbers: VICC GI 0174, VU-VICC-GI-0174
Study First Received: January 30, 2008
Last Updated: March 2, 2013
Health Authority: United States: Federal Government

Keywords provided by Vanderbilt-Ingram Cancer Center:
adenocarcinoma of the rectum
recurrent rectal cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer

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
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014