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Cetuximab in Treating Patients With Precancerous Lesions of the Upper Aerodigestive Tract

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00524017
Recruitment Status : Completed
First Posted : September 3, 2007
Last Update Posted : January 31, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center

Brief Summary:

RATIONALE: Monoclonal antibodies, such as cetuximab, can block abnormal cell growth in different ways. Some block the ability of abnormal cells to grow and spread. Others find abnormal cells and help kill them or carry cell-killing substances to them.

PURPOSE: This randomized phase II trial is studying how well cetuximab works in treating patients with precancerous lesions of the upper aerodigestive tract.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Precancerous Condition Biological: cetuximab Procedure: standard follow-up care Phase 2

Detailed Description:



  • To determine the histologic response rate in patients with high-risk, premalignant lesions of the upper aerodigestive tract treated with cetuximab.


  • To determine the clinical response rate in these patients.
  • To determine if patterns of EGFR component expression are altered in these patients.
  • To determine the change in status of genetic alterations, including loss of heterozygosity, in these patients.

OUTLINE: This is a multicenter study. Patients are stratified by lesion type (diffuse dysplasia vs recurrent dysplasia vs dysplastic lesions with 3p or 9p loss of heterozygosity [LOH]). Patients are randomized to 1 of 2 arms.

  • Arm I (treatment): Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity.
  • Arm II (control): Patients receive regular follow-up care. Patients have the option of receiving cetuximab after completion of the study.

In both arms, patients with persistent or recurrent high-grade dysplasia or dysplastic lesions with 3p or 9p LOH undergo surgical resection, if feasible, after week 8.

Tumor biopsy samples are obtained at baseline* and after week 8 for histologic and biomarker correlative studies. Tissue samples are analyzed by histopathology to determine histologic changes in post-treatment lesions and by IHC to measure expression and activation of EGFR signaling pathway components. LOH studies are also performed.

NOTE: *Paraffin-embedded tissue from the original diagnostic biopsy may be used for baseline assessment, if the diagnostic biopsy was performed within 3 months prior to study entry.

After completion of study therapy, patients are followed at approximately 1 month, every 3 months for 2 years, and then every 6 months for up to 5 years as per routine standard of care.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions
Study Start Date : May 2007
Primary Completion Date : December 2011
Study Completion Date : December 2011

Arm Intervention/treatment
Experimental: Arm I (treatment)
Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50 in the absence of disease progression or unacceptable toxicity.
Biological: cetuximab
given IV
No Intervention: Arm II (control)
Patients receive regular follow-up care
Procedure: standard follow-up care
Patients receive regular follow-up care

Primary Outcome Measures :
  1. Objective response based on histologic grade [ Time Frame: End of Treatment of Observation ]

Secondary Outcome Measures :
  1. Objective response based on clinical assessment (i.e., direct visualization of the lesion combined with histologic grade) [ Time Frame: End of Treatment of Observation ]
  2. Status of EGFR pathway components and molecular alterations in pre- and post-treatment biopsies [ Time Frame: End of Treatment of Observation ]
  3. Survival and lesion recurrence [ Time Frame: Up to year 5 after Treatment on Trial ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed high-risk, premalignant lesions of the upper aerodigestive tract, meeting one of the following criteria:

    • Unresectable, diffuse high-grade dysplasia, defined as moderate or severe dysplasia that is not assessable by physical examination and/or that cannot be excised by standard surgical techniques
    • previously treated HNSCC with persistent or recurrent high grade dysplasia with no evidence of head and neck malignancy for three months prior to enrollment or who have successfully completed therapy for head and neck malignancy more than 3 months prior to enrollment.
    • Dysplastic lesions with 3p or 9p loss of heterozygosity
  • Disease location amenable to endoscopic biopsy in an outpatient clinical setting or operative biopsy within the routine scheduling and practice of clinical care

    • No medical contraindication to biopsy of the target lesion
    • Pathology must be reviewed by the Johns Hopkins Hospital Department of Pathology


  • ECOG performance status 0-1
  • ANC > 1,000/mm³
  • Platelet count > 75,000/mm³
  • Creatinine clearance > 60 mL/min
  • Total serum bilirubin < 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study therapy
  • No concurrent illness likely to preclude study therapy or surgical resection
  • Patients with a history of a curatively treated malignancy are eligible provided they are disease-free and have a survival prognosis that exceeds 5 years
  • No evidence of clinically active interstitial lung disease

    • Patients with chronic, stable radiographic changes who are asymptomatic are eligible
  • No history or radiological evidence of pulmonary fibrosis
  • No acute myocardial infarction within the past 3 months
  • No uncontrolled angina, arrhythmia, or congestive heart failure
  • No evidence of other severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
  • No evidence of any other significant clinical disorder or laboratory finding that would preclude study participation
  • No known severe hypersensitivity to cetuximab or any of its excipients
  • No prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy
  • No severe abnormality of the cornea


  • See Disease Characteristics
  • Recovered from prior oncologic or other major surgery or biopsy
  • More than 30 days since prior non-approved or investigational drugs
  • No prior chemotherapy, radiotherapy, or surgery for the premalignant lesions
  • No prior EGFR-targeted agents (e.g., cetuximab, gefitinib, or erlotinib)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00524017

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Kentucky
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States, 40536-0093
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, New York
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10010
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Joseph Califano, MD Sidney Kimmel Comprehensive Cancer Center

Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT00524017     History of Changes
Other Study ID Numbers: J0644 CDR0000562250
P50CA096784 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
First Posted: September 3, 2007    Key Record Dates
Last Update Posted: January 31, 2012
Last Verified: January 2012

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
hypopharyngeal cancer
laryngeal cancer
lip and oral cavity cancer
nasopharyngeal cancer
oropharyngeal cancer
paranasal sinus and nasal cavity cancer
salivary gland cancer
precancerous condition

Additional relevant MeSH terms:
Head and Neck Neoplasms
Precancerous Conditions
Neoplasms by Site
Antineoplastic Agents