Celecoxib in Treating Patients With Head and Neck Cancer That Can Be Removed By Surgery

December 23, 2010 updated by: Centre Hospitalier Universitaire Vaudois

Evaluation of the Effect of Celecoxib on Angiogenesis Markers in Patients With Operable Head and Neck Squamous Cell Carcinoma

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving celecoxib before surgery may reduce the amount of normal tissue that needs to be removed. Collecting and storing samples of tumor tissue, blood, and urine from patients with head and neck cancer to study in the laboratory may help doctors learn more about the cancer and predict how well patients will respond to treatment with celecoxib.

PURPOSE: This phase I/II trial is studying changes in tumor cells and how well celecoxib works in treating patients with head and neck cancer that can be removed by surgery.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Evaluate the changes in molecular markers of angiogenesis before and after treatment with celecoxib in tumor tissues of patients with resectable head and neck squamous cell carcinoma.

Secondary

  • Evaluate the changes in molecular markers of angiogenesis before and after treatment with celecoxib in blood tissues of these patients.
  • Evaluate the effects of celecoxib on indirect measures of tumor perfusion, as measured by perfusion CT scan, in these patients.
  • Evaluate the effects of celecoxib on apoptosis and proliferation rate on tumor cells and on endothelial cells in these patients.
  • Identify potential new markers of the activity of cyclooxygenase-2 inhibitors and identify new pathways of potential interests by performing gene expression profiling of tumor tissues before and after exposure to celecoxib.

OUTLINE: This is an open-label, nonrandomized, uncontrolled study.

Patients undergo panendoscopy and tumor biopsy on day 0. Patients receive oral celecoxib twice daily beginning on day 1 and continuing for at least 14 days*. Patients then undergo definitive surgery.

NOTE: *Treatment continues until the day before surgery.

Tumor, blood, and urine samples are collected at baseline and periodically during study. Tumor quantification by perfusion CT scan is performed at baseline and after treatment with celecoxib. Biological markers are detected by immunohistochemistry and enzyme immunoassay. Blood vascular density, apoptosis, proliferation, and endothelial cell:tumor ratio are measured by indirect hemagglutination. Gene expression is measured by microarray analysis.

After surgery, patients are followed at 4 weeks and then periodically thereafter.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Lausanne, Switzerland, CH-1011
        • Centre hospitalier universitaire vaudois

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed or high clinical suspicion of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx

    • No carcinoma of sinonasal or nasopharynx

  • Clinical stage T1-4, N0-2, M0 disease

    • Tumor must be considered resectable with planned surgical excision
    • No lymph nodes > 6 cm (N3)
    • No distant metastasis

PATIENT CHARACTERISTICS:

  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Creatinine clearance ≥ 60 mL/min
  • AST and ALT ≤ 2.5 times ULN
  • Bilirubin normal
  • History of prior malignancy allowed if there is no evidence of recurrence or metastases at the time of screening
  • No comorbidity that precludes operability
  • No known liver impairment
  • Known recent gastric or duodenal ulcer allowed if treated for > 6 weeks prior to study enrollment
  • No known hypersensitivity to celecoxib
  • No known allergic reactions to sulfonamides, aspirin, or other NSAIDs
  • No psychological, familial, sociological, or geographical condition that would interfere with study compliance and follow-up schedule
  • Not pregnant or nursing
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • More than 2 months since prior and no other concurrent anticancer or investigational drugs
  • More than 2 weeks since prior and no other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids
  • No prior radiotherapy to the head and neck region
  • No concurrent radiotherapy
  • No concurrent therapeutic anticoagulation

  • No concurrent administration of any of the following:

    • Other cyclooxygenase-2 inhibitors

    • Aspirin

      • Low-dose aspirin for cardiovascular prophylaxis allowed
    • Aluminum and magnesium-containing antacids
    • ACE inhibitors
    • Furosemide
    • Known inhibitors of P450 2C9 (e.g., fluconazole, fluoxetine, fluvoxamin, isoniazid, omeprazole)
    • Known inducers of P450 2C9 (e.g., rifampin)
    • Lithium
    • Acenocoumarol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Molecular markers of angiogenesis in tumor tissues (PGE2, VEGF, MMP-9, sFlt-1, ERK phosphorylation, PKB phosphorylation, and ErbB2 levels)

Secondary Outcome Measures

Outcome Measure
Molecular markers in plasma (VEGF, MMP-9, and sFlt1)
Molecular marker in urine (PGE2)
Apoptosis/proliferation in tumor cells and endothelial cells
Gene expression profiling in fresh tumor tissues (Erb-B2, c-IAP-2, PAI-1, MAPK-4, integrin α V, N-CAM, caspase 6, ErbB2 transducer, angiopoietin like-2, interleukin-8, and MMP13)
Tumor perfusion imaging by perfusion CT scan

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire Vaudois

Investigators

  • Study Chair: Francois Luthi, MD, Centre hospitalier universitaire vaudois

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Study Registration Dates

First Submitted

July 26, 2006

First Submitted That Met QC Criteria

July 26, 2006

First Posted (Estimate)

July 27, 2006

Study Record Updates

Last Update Posted (Estimate)

December 24, 2010

Last Update Submitted That Met QC Criteria

December 23, 2010

Last Verified

January 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000490047
  • CHUV-CEPO-161-05
  • EU-20627

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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