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Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions

Phase 2
18 Years
Not Enrolling
Head and Neck Cancer, Precancerous Condition

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Trial Information

Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions



- 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

Inclusion Criteria


- 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

- 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

- 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)

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Objective response based on histologic grade

Outcome Time Frame:

End of Treatment of Observation

Safety Issue:


Principal Investigator

Joseph Califano, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:

J0644 CDR0000562250



Start Date:

May 2007

Completion Date:

December 2011

Related Keywords:

  • Head and Neck Cancer
  • Precancerous Condition
  • hypopharyngeal cancer
  • laryngeal cancer
  • lip and oral cavity cancer
  • nasopharyngeal cancer
  • oropharyngeal cancer
  • paranasal sinus and nasal cavity cancer
  • salivary gland cancer
  • precancerous condition
  • Head and Neck Neoplasms
  • Precancerous Conditions



University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
University of Chicago Cancer Research Center Chicago, Illinois  60637
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
NYU Cancer Institute at New York University Medical Center New York, New York  10016
Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
Greenebaum Cancer Center at University of Maryland Medical Center Baltimore, Maryland  21201
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Lucille P. Markey Cancer Center at University of Kentucky Lexington, Kentucky  40536-0093
UPMC Cancer Centers Pittsburgh, Pennsylvania  15232